To Örebro University

oru.seÖrebro University Publications
Change search
Refine search result
12 1 - 50 of 73
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Bateman, Daniel R.
    et al.
    Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA; Indiana University Center for Aging Research, Regenstrief Institute, Indianapolis, Indiana, USA.
    Sascha, Gill
    Department of Clinical Neurosciences; and the Ron and Rene Ward Centre for Healthy Brain Aging Research; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
    Hu, Sophie
    Community Health Sciences, and O’Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada.
    Foster, Erin D.
    Ruth Lilly Medical Library, Indiana University School of Medicine, Indianapolis, Indiana, USA; University of California Berkeley, Berkeley, CA, USA.
    Ruthirakuhan, Myuri T.
    Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Ontario, Canada.
    Sellek, Allis F.
    The Alzheimer Foundation of Costa Rica, Costa Rica.
    Mortby, Moyra E.
    School of Psychology, University of New South Wales, Sydney, New South Wales, Australia; Neuroscience Research Australia, University of New South Wales, Sydney, New South Wales, Australia.
    Matušková, Veronika
    International Clinical Research Center, St. Anne’s University Hospital Brno, Brno, Czech Republic; Memory Disorders Clinic, Department of Neurology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic.
    Pin, Kok
    Department of Neurology, National Neuroscience Institute, Singapore, Singapore.
    Tarawneh, Rawan M.
    Department of Neurology, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
    Freund-Levi, Yvonne
    Örebro University, School of Medical Sciences. Center for Alzheimer Research, Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
    Kumar, Sanjeev
    Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Ontario, Canada.
    Gauthier, Serge
    McGill Center for Studies in Aging, McGill University, Montreal, Quebec, Canada.
    Rosenberg, Paul B.
    Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral, Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
    Ferreira deOliveira, Fabricio
    Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, São Paulo, Brazil.
    Devanand, D. P.
    New York State Psychiatric Institute and Department of Psychiatry and Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
    Ballard, Clive
    College of Medicine and Health, The University of Exeter, Exeter, UK.
    Ismail, Zahinoor
    Department of Clinical Neurosciences; and the Ron and Rene Ward Centre for Healthy Brain Aging Research; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Community Health Sciences, and O’Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada; Department of Psychiatry, and the Mathison Centre for Mental Health Research & Education, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
    Agitation and impulsivity in mid and late life as possible riskmarkers for incident dementia2020In: Alzheimer’s & Dementia: Translational Research & Clinical Interventions, E-ISSN 2352-8737, Vol. 6, no 1, article id e12016Article, review/survey (Refereed)
    Abstract [en]

    To identify knowledge gaps regarding new-onset agitation and impulsivity prior to onsetof cognitive impairment or dementia the International Society to Advance Alzheimer’sResearch and Treatment Neuropsychiatric Syndromes (NPS) Professional InterestAreaconducted a scoping review. Extending a series of reviews exploring the pre-dementiarisk syndrome Mild Behavioral Impairment (MBI), we focused on late-onset agitationand impulsivity (the MBI impulse dyscontrol domain) and risk of incident cognitivedecline and dementia. This scoping review of agitation and impulsivity pre-dementiasyndromes summarizes the current biomedical literature in terms of epidemiology,diagnosis andmeasurement, neurobiology, neuroimaging, biomarkers, course and prognosis,treatment, and ongoing clinical trials. Validations for pre-dementia scales suchas the MBI Checklist, and incorporation into longitudinal and intervention trials, areneeded to better understand impulse dyscontrol as a risk factor for mild cognitiveimpairment and dementia.

  • 2.
    Bloniecki, V.
    et al.
    Karolinska Institutet, NVS, Stockholm, Sweden.
    Freund-Levi, Yvonne
    Karolinska Institutet, NVS, Stockholm, Sweden.
    Aarsland, D.
    Sahlgrenska University Hospital, Stockholm, Sweden.
    Blennow, K.
    Sahlgrenska University Hospital, Stockholm, Sweden.
    Agitation - relation to clinical and dementia biomarkers in cerebrospinal fluid2012In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 19, no s1, p. 112-112Article in journal (Other academic)
  • 3.
    Bloniecki, Victor
    et al.
    Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institute, Stockholm, Sweden.
    Aarsland, Dag
    Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institute, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden; Center for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
    Blennow, Kaj
    Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
    Cummings, Jeffrey
    Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA.
    Falahati, Farshad
    Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institute, Stockholm, Sweden.
    Winblad, Bengt
    Department of Neurobiology, Caring Sciences and Society (NVS), Center for Alzheimer Research, Division of Neurogeriatrics, Karolinska Institute, Huddinge, Sweden.
    Freund-Levi, Yvonne
    Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institute, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Effects of Risperidone and Galantamine Treatment on Alzheimer's Disease Biomarker Levels in Cerebrospinal Fluid2017In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 57, no 2, p. 387-393Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Treatment for neuropsychiatric symptoms (NPS) in dementia is insufficient. Antipsychotics and acetylcholinesterase inhibitors are used generating symptomatic improvements in behavior and cognition, but few studies have investigated their effect on Alzheimer's disease (AD) biomarkers in cerebrospinal fluid (CSF).

    OBJECTIVE: This is a secondary analysis based on an earlier clinical trial comparing the treatment effects on NPS. The aim of this study was to examine whether treatment with risperidone and galantamine affect levels of the biomarkers T-Tau, P-Tau, Aβ1-42, and Aβ42/40-ratio in CSF. The secondary aim was to test if baseline levels of these biomarkers are associated with the clinical course of NPS.

    METHODS: 83 patients (mean + SD 77.9.6±7.7 years) with dementia and NPS were randomized to galantamine (n = 44) or risperidone (n = 39) treatment. CSF samples were collected at baseline and after 12 weeks.

    RESULTS: Changes in levels of biomarkers between the two treatment groups did not differ significantly. Low baseline levels of Aβ1 - 42 was significantly associated with reduction of irritability at follow up. Low baseline levels of Aβ1-42, Aβ42/40, and P-Tau were significant correlates of reduction in appetite and eating disorders. CSF Aβ1-42 levels in patients treated with risperidone were significantly decreased at follow up, showing an 8% (40 pg/mL) reduction as compared with baseline (p = 0.03).

    CONCLUSIONS: Our results suggest that risperidone may affect the CSF profile of AD biomarkers indicating more amyloid pathology. Treatment with galantamine did not affect the CSF biomarkers in any direction. The AD CSF biomarkers displayed correlations with specific NPS suggesting potential research questions to be pursued.

  • 4.
    Bloniecki, Victor
    et al.
    Division of Clinical Geriatrics, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Aarsland, Dag
    Center for Alzheimer Research, Division for Neurogeriatrics, Department of Neurobiology, Caring Sciences and Society (NVS), Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; Center for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
    Cummings, Jeffrey
    Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, Nev., USA.
    Blennow, Kaj
    Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
    Freund-Levi, Yvonne
    Division of Clinical Geriatrics, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Agitation in dementia: relation to core cerebrospinal fluid biomarker levels2014In: Dementia and Geriatric Cognitive Disorders Extra, E-ISSN 1664-5464, Vol. 4, no 2, p. 335-43Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The objective of this study was to examine the associations of agitation with the cerebrospinal fluid dementia biomarkers total-tau (T-tau), phosphorylated-tau (P-tau) and Aβ1-42.

    METHODS: One hundred patients (mean age ± SD, 78.6 ± 7.5 years) with dementia and neuropsychiatric symptoms, of whom 67% were female, were included. Agitation was measured using the Cohen-Mansfield Agitation Inventory (CMAI; 46.5 ± 11.8 points).

    RESULTS: Total CMAI correlated with T-tau [rs (31) = 0.36, p = 0.04] and P-tau [rs (31) = 0.35, p = 0.05] in patients with Alzheimer's disease (AD; n = 33) but not in the total dementia population (n = 95).

    CONCLUSIONS: Our results suggest that tau-mediated pathology including neurofibrillary tangles and the intensity of the disease process might be associated with agitation in AD.

  • 5.
    Bloniecki, Victor
    et al.
    Dermatology and Venereology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    Ulfvarson, J.
    Department of Neurobiology, Care Sciences and Society, Division of Nursing, Karolinska Institutet, Stockholm, Sweden.
    Javanshiri, K.
    Department of Clinical Sciences Lund, Division of Pathology, Lund University, Lund, Sweden.
    Hagman, G.
    Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Center for Alzheimer Research, Karolinska Institute, Stockholm, Sweden, Theme Aging, Karolinska University Hospital, Stockholm, Sweden.
    Freund-Levi, Yvonne
    Örebro University, School of Medical Sciences. Department of Clinical Science and Education, Södersjukhuset Karolinska Institutet, Stockholm, Sweden; Department of Geriatrics, University Hospital Örebro, Sweden; Södertälje Hospital, Södertälje, Sweden.
    Nordström, A.
    Department of Public Health and Clinical Medicine, Section of Sustainable Health, Umeå University, Umeå, Sweden; Department of Health Sciences, The Swedish Winter Sports Research Centre, Mid Sweden University, Östersund, Sweden; School of Sport Sciences, UiT the Arctic University of Norway, Tromsø, Norway.
    The Geras Solutions Cognitive Test for Assessing Cognitive Impairment: Normative Data from a Population-Based Cohort2023In: The Journal of Prevention of Alzheimer's Disease, ISSN 2274-5807, E-ISSN 2426-0266, Vol. 2, no 10, p. 207-211Article in journal (Refereed)
    Abstract [en]

    Background: There is a need for the development of accurate, accessible and efficient screening instruments, focused on early-stage detection of neurocognitive disorders. The Geras Solutions cognitive test (GSCT) has showed potential as a digital screening tool for cognitive impairment but normative data are needed.

    Objective: The aim of this study was to obtain normative data for the GSCT in cognitively healthy patients, investigate the effects of gender and education on test scores as well as examine test-retest reliability.

    Methods: The population in this study consisted of 144 cognitively healthy subjects (MMSE>26) all at the age of 70 who were earlier included in the Healthy Aging Initiative Study conducted in Umea, Sweden. All patients conducted the GSCT and a subset of patients (n=32) completed the test twice in order to establish test-retest reliability.

    Results: The mean GSCT score was 46.0 (+/- 4.5) points. High level of education (>12 years) was associated with a high GSCT score (p = 0.02) while gender was not associated with GSCT outcomes (p = 0.5). GSCT displayed a high correlation between test and retest (r(30) = 0.8, p <0.01).

    Conclusion: This study provides valuable information regarding normative test-scores on the GSCT for cognitively healthy individuals and indicates education level as the most important predictor of test outcome. Additionally, the GSCT appears to display a good test-retest reliability further strengthening the validity of the test.

  • 6.
    Bloniecki, Victor
    et al.
    Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; Department of Dermatology, Karolinska University Hospital, Solna, Sweden.
    Zetterberg, Henrik
    Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; UK Dementia Research Institute at UCL, London, UK; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
    Aarsland, Dag
    Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Center for Age-Related Diseases, Stavanger University Hospital, Stavanger, Norway.
    Vannini, Patrizia
    Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
    Kvartsberg, Hlin
    Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
    Winblad, Bengt
    Department of Neurobiology, Caring Sciences and Society (NVS), Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden; Theme Aging, Karolinska University Hospital, Huddinge, Sweden.
    Blennow, Kaj
    Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
    Freund-Levi, yfi
    Örebro University, School of Medical Sciences. Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; Department of Psychiatry in Region Örebro County and School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Old Age Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
    Are neuropsychiatric symptoms in dementia linked to CSF biomarkers of synaptic and axonal degeneration?2020In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 12, no 1, article id 153Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The underlying disease mechanism of neuropsychiatric symptoms (NPS) in dementia remains unclear. Cerebrospinal fluid (CSF) biomarkers for synaptic and axonal degeneration may provide novel neuropathological information for their occurrence. The aim was to investigate the relationship between NPS and CSF biomarkers for synaptic (neurogranin [Ng], growth-associated protein 43 [GAP-43]) and axonal (neurofilament light [NFL]) injury in patients with dementia.

    METHODS: A total of 151 patients (mean age ± SD, 73.5 ± 11.0, females n = 92 [61%]) were included, of which 64 had Alzheimer's disease (AD) (34 with high NPS, i.e., Neuropsychiatric Inventory (NPI) score > 10 and 30 with low levels of NPS) and 18 were diagnosed with vascular dementia (VaD), 27 with mixed dementia (MIX), 12 with mild cognitive impairment (MCI), and 30 with subjective cognitive impairment (SCI). NPS were primarily assessed using the NPI. CSF samples were analyzed using enzyme-linked immunosorbent assays (ELISAs) for T-tau, P-tau, Aβ1-42, Ng, NFL, and GAP-43.

    RESULTS: No significant differences were seen in the CSF levels of Ng, GAP-43, and NFL between AD patients with high vs low levels of NPS (but almost significantly decreased for Ng in AD patients < 70 years with high NPS, p = 0.06). No significant associations between NPS and CSF biomarkers were seen in AD patients. In VaD (n = 17), negative correlations were found between GAP-43, Ng, NFL, and NPS.

    CONCLUSION: Our results could suggest that low levels of Ng may be associated with higher severity of NPS early in the AD continuum (age < 70). Furthermore, our data may indicate a potential relationship between the presence of NPS and synaptic as well as axonal degeneration in the setting of VaD pathology.

  • 7.
    Bos, Isabelle
    et al.
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
    Verhey, Frans R.
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
    Ramakers, Inez H. G. B.
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
    Jacobs, Heidi I. L.
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
    Soininen, Hilkka
    Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland; Neurocenter & Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
    Freund-Levi, Yvonne
    Department of Neurobiology, Caring Sciences and Society (NVS), Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Hampel, Harald
    AXA Research Fund and UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie (UPMC), Paris, France; Institut du cerveau et de la moelle (ICM), Hôpital Pitié-Salpêtrière, Paris, France.
    Tsolaki, Magda
    Aristotle University of Thessaloniki, Memory and Dementia Center, 3rd Department of Neurology, “G Papanicolau” General Hospital, Thessaloniki, Greece.
    Wallin, Åsa K.
    Department of Clinical Sciences Malmö, Clinical Memory Research Unit, Lund University, Lund, Sweden.
    van Buchem, Mark A.
    Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
    Oleksik, Ania
    Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
    Verbeek, Marcel M.
    Departments of Neurology and Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen, The Netherlands.
    Olde Rikkert, Marcel
    Radboudumc Alzheimer Centre, Department of Geriatric Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
    van der Flier, Wiesje M.
    Department of Neurology, Alzheimer Centre, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
    Scheltens, Philip
    Department of Neurology, Alzheimer Centre, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
    Aalten, Pauline
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
    Visser, Pieter Jelle
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands; Department of Neurology, Alzheimer Centre, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
    Vos, Stephanie J. B.
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
    Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline2017In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 9, no 1, article id 101Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cerebrovascular disease (CVD) and amyloid-β (Aβ) often coexist, but their influence on neurodegeneration and cognition in predementia stages remains unclear. We investigated the association between CVD and Aβ on neurodegenerative markers and cognition in patients without dementia.

    METHODS: We included 271 memory clinic patients with subjective or objective cognitive deficits but without dementia from the BioBank Alzheimer Center Limburg cohort (n = 99) and the LeARN (n = 50) and DESCRIPA (n = 122) multicenter studies. CSF Aβ1-42 and white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) scans were used as measures of Aβ and CVD, respectively. Individuals were classified into four groups based on the presence (+) or absence (-) of Aβ and WMH. We investigated differences in phosphorylated tau, total tau (t-tau), and medial temporal lobe atrophy (MTA) between groups using general linear models. We examined cognitive decline and progression to dementia using linear mixed models and Cox proportional hazards models. All analyses were adjusted for study and demographics.

    RESULTS: MTA and t-tau were elevated in the Aβ - WMH+, Aβ + WMH-, and Aβ + WMH+ groups. MTA was most severe in the Aβ + WMH+ group compared with the groups with a single pathology. Both WMH and Aβ were associated with cognitive decline, but having both pathologies simultaneously was not associated with faster decline.

    CONCLUSIONS: In the present study, we found an additive association of Aβ and CVD pathology with baseline MTA but not with cognitive decline. Because our findings may have implications for diagnosis and prognosis of memory clinic patients and for future scientific research, they should be validated in a larger sample with longer follow-up.

  • 8.
    Bos, Isabelle
    et al.
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
    Verhey, Frans R
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
    Ramakers, Inez H G B
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
    Jacobs, Heidi I L
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
    Soininen, Hilkka
    Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland; Neurocenter and Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
    Freund-Levi, Yvonne
    Department of Neurobiology, Caring Sciences and Society (NVS), Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Hampel, Harald
    Institut du cerveau et de la moelle (ICM), Hôpital Pitié-Salpêtrière, Paris, France; AXA Research Fund and UPMC Chair Sorbonne Universités, Université Pierre et Marie Curie (UPMC), Paris, France.
    Tsolaki, Magda
    Memory and Dementia Center, 3rd Department of Neurology, Aristotle University of Thessaloniki, G Papanicolau, General Hospital, Thessaloniki, Greece.
    Wallin, Åsa K
    Department of Clinical Sciences Malmö, Clinical Memory Research Unit, Lund University, Lund, Sweden.
    van Buchem, Mark A
    Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
    Oleksik, Ania
    Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
    Verbeek, Marcel M
    Departments of Neurology and Laboratory Medicine, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen, The Netherlands.
    Rikkert, Marcel Olde
    Radboudumc Alzheimer Centre, Department of Geriatric Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
    van der Flier, Wiesje M
    Department of Neurology, Alzheimer Centre, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
    Scheltens, Philip
    Department of Neurology, Alzheimer Centre, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
    Aalten, Pauline
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
    Visser, Pieter Jelle
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands; Department of Neurology, Alzheimer Centre, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
    Vos, Stephanie J B
    Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
    Correction to: Cerebrovascular and amyloid pathology in predementia stages2018In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 10, no 56Article in journal (Refereed)
    Abstract [en]

    Upon publication of this article [1], it was noticed that there were some inconsistencies in Tables 1, 2 and 3. Some of the superscript letters were incorrectly assigned. Please see below the correct tables.

  • 9.
    Bos, Isabelle
    et al.
    Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience Maastricht University, Maastricht, Netherlands.
    Vos, Stephanie J. B.
    Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience Maastricht University, Maastricht, Netherlands.
    Jansen, Willemijn J.
    Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience Maastricht University, Maastricht, Netherlands.
    Vandenberghe, Rik
    University Hospital Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences KU Leuven, Leuven, Belgium.
    Gabel, Silvy
    Laboratory for Cognitive Neurology, Department of Neurosciences KU Leuven, Leuven, Belgium; Alzheimer Research Centre KU Leuven, Leuven, Belgium.
    Estanga, Ainara
    Center for Research and Advanced Therapies CITA-Alzheimer Foundation, San Sebastián, Spain.
    Ecay-Torres, Mirian
    Center for Research and Advanced Therapies CITA-Alzheimer Foundation, San Sebastián, Spain.
    Tomassen, Jori
    Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center VU University Amsterdam, Amsterdam, Netherlands.
    den Braber, Anouk
    Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center VU University Amsterdam, Amsterdam, Netherlands; Department of Biological Psychology VU University Amsterdam, Amsterdam, Netherlands.
    Lleó, Alberto
    Department of Neurology Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
    Sala, Isabel
    Department of Neurology Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
    Wallin, Anders
    Section for Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden.
    Kettunen, Petronella
    Section for Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
    Molinuevo, José L.
    Alzheimer's Disease & Other Cognitive Disorders Unit, Hopsital Clínic Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain; Barcelona Beta Brain Research Center, Unversitat Pompeu Fabra, Barcelona, Spain.
    Rami, Lorena
    Alzheimer's Disease & Other Cognitive Disorders Unit, Hopsital Clínic Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
    Chetelat, Gaël
    Institut National de la Santé et de la Recherche Médicale UMR-S U1237, Université de Caen-Normandie GIP Cyceron, Caen, France.
    de la Sayette, Vincent
    Institut National de la Santé et de la Recherche Médicale U1077, Université de Caen Normandie Ecole Pratique des Hautes Etudes, Caen, France; CHU de Caen Service de Neurologie, Caen, France.
    Tsolaki, Magda
    1st Department of Neurology, University General Hospital of Thessaloniki AHEPA, Thessaloniki, Greece.
    Freund-Levi, Yvonne
    Division of Clinical Geriatrics, Department of Neurobiology, Caring Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden; Department of Psychiatry, Norrtälje Hospital Tiohundra, Norrtälje, Sweden.
    Johannsen, Peter
    Danish Dementia Research Centre, Rigshospitalet, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark.
    Novak, Gerald P.
    Janssen Pharmaceutical Research and Development, Titusville, NJ, United States.
    Ramakers, Inez
    Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience Maastricht University, Maastricht, Netherlands.
    Verhey, Frans R.
    Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience Maastricht University, Maastricht, Netherlands.
    Visser, Pieter Jelle
    Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, School for Mental Health and Neuroscience Maastricht University, Maastricht, Netherlands.
    Amyloid-β, Tau, and Cognition in Cognitively Normal Older Individuals: Examining the Necessity to Adjust for Biomarker Status in Normative Data.2018In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 10, article id 193Article in journal (Refereed)
    Abstract [en]

    We investigated whether amyloid-β (Aβ) and tau affected cognition in cognitively normal (CN) individuals, and whether norms for neuropsychological tests based on biomarker-negative individuals would improve early detection of dementia. We included 907 CN individuals from 8 European cohorts and from the Alzheimer's disease Neuroimaging Initiative. All individuals were aged above 40, had Aβ status and neuropsychological data available. Linear mixed models were used to assess the associations of Aβ and tau with five neuropsychological tests assessing memory (immediate and delayed recall of Auditory Verbal Learning Test, AVLT), verbal fluency (Verbal Fluency Test, VFT), attention and executive functioning (Trail Making Test, TMT, part A and B). All test except the VFT were associated with Aβ status and this influence was augmented by age. We found no influence of tau on any of the cognitive tests. For the AVLT Immediate and Delayed recall and the TMT part A and B, we calculated norms in individuals without Aβ pathology (Aβ- norms), which we validated in an independent memory-clinic cohort by comparing their predictive accuracy to published norms. For memory tests, the Aβ- norms rightfully identified an additional group of individuals at risk of dementia. For non-memory test we found no difference. We confirmed the relationship between Aβ and cognition in cognitively normal individuals. The Aβ- norms for memory tests in combination with published norms improve prognostic accuracy of dementia.

  • 10.
    Bos, Isabelle
    et al.
    Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, Netherlands.
    Vos, Stephanie J.
    Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, Netherlands.
    Frölich, Lutz
    Department of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany.
    Kornhuber, Johannes
    Department of Psychiatry and Psychotherapy, Friedrich-Alexander University of Erlangen-Nürnberg, Erlangen, Germany.
    Wiltfang, Jens
    Department of Psychiatry and Psychotherapy, University Medical Center (UMC), Georg-August-University, Göttingen, Germany.
    Maier, Wolfgang
    Department of Psychiatry and Psychotherapy, University of Bonn, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
    Peters, Oliver
    Department of Psychiatry and Psychotherapy, Charité Berlin, Berlin, Germany.
    Rüther, Eckhart
    Department of Psychiatry and Psychotherapy, University of Göttingen, Göttingen, Germany.
    Engelborghs, Sebastiaan
    Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium; Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium.
    Niemantsverdriet, Ellis
    Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium.
    De Roeck, Ellen Elisa
    Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium; Department of Clinical and Lifespan Psychology, Vrije Universiteit Brussel, Brussels, Belgium.
    Tsolaki, Magda
    3rd Department of Neurology, Aristotle University of Thessaloniki, Memory and Dementia Center, “G Papanicolau” General Hospital, Thessaloniki, Greece.
    Freund-Levi, Yvonne
    Division of Clinical Geriatrics, Department of Neurobiology, Caring Sciences and Society (NVS), Karolinska Institutet, Huddinge, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Johannsen, Peter
    Danish Dementia Research Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
    Vandenberghe, Rik
    Department of Neurology, University of Hospital Leuven, Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Belgium.
    Lleó, Alberto
    Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
    Alcolea, Daniel
    Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
    Frisoni, Giovanni B.
    Geneva Neuroscience Center, University Hospital and University of Geneva, Geneva, Switzerland; IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
    Galluzzi, Samantha
    IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
    Nobili, Flavio
    Clinical Neurology, Department of Neurosciences (DINOGMI), University of Genoa and IRCCS AOU San Martino-IST, Genoa, Italy.
    Morbelli, Silvia
    Nuclear Medicine, Department of Health Science (DISSAL), University of Genoa IRCCS AOU San Martino-IST, Genoa, Italy.
    Drzezga, Alexander
    Department of Nuclear Medicine, University of Cologne, Cologne, Germany.
    Didic, Mira
    AP-HM Hôpitaux de la Timone, Service de Neurologie et Neuropsychologie, Marseille, France; Aix-Marseille Université, INSERM, Institut de Neurosciences des Systèmes, Marseille, France.
    van Berckel, Bart N.
    Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
    Salmon, Eric
    Department of Neurology and Memory Clinic, CHU Liège, Liège, Belgium; GIGA-CRC in vivo Imaging, University of Liège, Liège, Belgium.
    Bastin, Christine
    GIGA-CRC in vivo Imaging, University of Liège, Liège, Belgium.
    Dauby, Solene
    Department of Neurology and Memory Clinic, CHU Liège, Liège, Belgium.
    Santana, Isabel
    Department of Neurology and Memory Clinic, CHU Liège, Liège, Belgium.
    Baldeiras, Inês
    Center for Neuroscience and Cell Biology, Faculty of Medicine, Department of Neurology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
    de Mendonça, Alexandre
    Institute of Molecular Medicine and Faculty of Medicine, University of Lisbon, Portugal.
    Silva, Dina
    Institute of Molecular Medicine and Faculty of Medicine, University of Lisbon, Portugal.
    Wallin, Anders
    Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Nordlund, Arto
    Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Coloma, Preciosa M.
    Real World Data Science (RWD-S) Neuroscience and Established Products, F. Hoffmann-La Roche Ltd. Pharmaceuticals Division, Basel, Switzerland.
    Wientzek, Angelika
    PDB RWD (Real World Data) Team, Roche Products Limited, Welwyn Garden City, UK; Epidemiologische Beratung und Literatur-Recherche “conepi”, Herrsching, Germany.
    Alexander, Myriam
    PDB RWD (Real World Data) Team, Roche Products Limited, Welwyn Garden City, UK.
    Novak, Gerald P.
    Janssen Pharmaceutical Research and Development, Titusville, NJ, USA.
    Gordon, Mark Forrest
    Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT, USA.
    Wallin, Åsa K.
    Department of Clinical Sciences Malmö, Clinical Memory Research Unit, Lund University, Lund, Sweden.
    Hampel, Harald
    Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, AXA Research Fund & UPMC Chair, Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A), Paris, France; Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris, France.
    Soininen, Hilkka
    Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland; Neurocenter, Neurology, Kuopio University Hospital, Kuopio, Finland.
    Herukka, Sanna-Kaisa
    Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland; Neurocenter, Neurology, Kuopio University Hospital, Kuopio, Finland.
    Scheltens, Philip
    Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
    Verhey, Frans R.
    Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, Netherlands.
    Visser, Pieter Jelle
    Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht, Netherlands; Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, Netherlands.
    The frequency and influence of dementia risk factors in prodromal Alzheimer's disease2017In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 56, p. 33-40Article in journal (Refereed)
    Abstract [en]

    We investigated whether dementia risk factors were associated with prodromal Alzheimer's disease (AD) according to the International Working Group-2 and National Institute of Aging-Alzheimer's Association criteria, and with cognitive decline. A total of 1394 subjects with mild cognitive impairment from 14 different studies were classified according to these research criteria, based on cognitive performance and biomarkers. We compared the frequency of 10 risk factors between the subgroups, and used Cox-regression to examine the effect of risk factors on cognitive decline. Depression, obesity, and hypercholesterolemia occurred more often in individuals with low-AD-likelihood, compared with those with a high-AD-likelihood. Only alcohol use increased the risk of cognitive decline, regardless of AD pathology. These results suggest that traditional risk factors for AD are not associated with prodromal AD or with progression to dementia, among subjects with mild cognitive impairment. Future studies should validate these findings and determine whether risk factors might be of influence at an earlier stage (i.e., preclinical) of AD.

  • 11.
    Bos, Isabelle
    et al.
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
    Vos, Stephanie
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
    Verhey, Frans
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
    Scheltens, Philip
    Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.
    Teunissen, Charlotte
    Neurochemistry Lab and Biobank, Department of Clinical Chemistry, VU University Medical Center, Amsterdam Neuroscience, Amsterdam, the Netherlands.
    Engelborghs, Sebastiaan
    Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium; Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
    Sleegers, Kristel
    Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Neurodegenerative Brain Diseases Group, Center for Molecular Neurology, VIB, Antwerp, Belgium.
    Frisoni, Giovanni
    University of Geneva, Geneva, Switzerland; IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
    Blin, Olivier
    Mediterranean Institute of Cognitive Neuroscience, Aix Marseille University, Marseille, France.
    Richardson, Jill C.
    Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevenage, UK.
    Bordet, Régis
    University of Lille, Inserm, CHU Lille, Lille, France.
    Tsolaki, Magda
    1st Department of Neurology, AHEPA University Hospital, Makedonia, Thessaloniki, Greece.
    Popp, Julius
    Geriatric Psychiatry, Department of Mental Health and Psychiatry, Geneva University Hospitals, Geneva, Switzerland; Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
    Peyratout, Gwendoline
    Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
    Martinez-Lage, Pablo
    Department of Neurology, Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, San Sebastian, Spain.
    Tainta, Mikel
    Department of Neurology, Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, San Sebastian, Spain.
    Lleó, Alberto
    Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
    Johannsen, Peter
    Danish Dementia Research Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
    Freund-Levi, Yvonne
    Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Psychiatry Norrtälje Hospital Tiohundra, Norrtäije, Sweden.
    Frölich, Lutz
    Department of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany.
    Vandenberghe, Rik
    University Hospital Leuven, Leuven, Belgium.
    Westwood, Sarah
    University of Oxford, Oxford, United Kingdom.
    Dobricic, Valerija
    Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany.
    Barkhof, Frederik
    Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands; Institutes of Neurology and Healthcare Engineering, University College London, London, UK.
    Legido-Quigley, Cristina
    Steno Diabetes Center, Copenhagen, Denmark; King's College London, London, UK.
    Bertram, Lars
    Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany; School of Public Health, Imperial College London, London, UK; Department of Psychology, University of Oslo, Oslo, Norway.
    Lovestone, Simon
    University of Oxford, Oxford, United Kingdom.
    Streffer, Johannes
    Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Early Clinial Neurology, UCB Biopharma SPRL, Braine-l'Alleud, Belgium.
    Andreasson, Ulf
    Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, University of Gothenburg, Institute of Neuroscience and Physiology, Mölndal, Sweden.
    Blennow, Kaj
    Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, University of Gothenburg, Institute of Neuroscience and Physiology, Mölndal, Sweden.
    Zetterberg, Henrik
    Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, University of Gothenburg, Institute of Neuroscience and Physiology, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; UK Dementia Research Institute, London, UK.
    Visser, Pieter Jelle
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands; Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands.
    Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum2019In: Alzheimer's & Dementia: Journal of the Alzheimer's Association, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 15, no 5, p. 644-654Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: We investigated relations between amyloid-β (Aβ) status, apolipoprotein E (APOE) ε4, and cognition, with cerebrospinal fluid markers of neurogranin (Ng), neurofilament light (NFL), YKL-40, and total tau (T-tau).

    METHODS: We included 770 individuals with normal cognition, mild cognitive impairment, and Alzheimer's disease (AD)-type dementia from the EMIF-AD Multimodal Biomarker Discovery study. We tested the association of Ng, NFL, YKL-40, and T-tau with Aβ status (Aβ- vs. Aβ+), clinical diagnosis APOE ε4 carriership, baseline cognition, and change in cognition.

    RESULTS: Ng and T-tau distinguished between Aβ+ from Aβ- individuals in each clinical group, whereas NFL and YKL-40 were associated with Aβ+ in nondemented individuals only. APOE ε4 carriership did not influence NFL, Ng, and YKL-40 in Aβ+ individuals. NFL was the best predictor of cognitive decline in Aβ+ individuals across the cognitive spectrum.

    DISCUSSION: Axonal degeneration, synaptic dysfunction, astroglial activation, and altered tau metabolism are involved already in preclinical AD. NFL may be a useful prognostic marker.

  • 12.
    Delvenne, Aurore
    et al.
    Department of Psychiatry and Neuropsychology, Alzheimer Centrum Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
    Gobom, Johan
    Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
    Tijms, Betty
    Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands.
    Bos, Isabelle
    Department of Psychiatry and Neuropsychology, Alzheimer Centrum Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands.
    Reus, Lianne M.
    Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands.
    Dobricic, Valerija
    Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany.
    Kate, Mara Ten
    Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands .
    Verhey, Frans
    Department of Psychiatry and Neuropsychology, Alzheimer Centrum Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
    Ramakers, Inez
    Department of Psychiatry and Neuropsychology, Alzheimer Centrum Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
    Scheltens, Philip
    Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands.
    Teunissen, Charlotte E.
    Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam University Medical Centers (AUMC), Amsterdam Neuroscience, the Netherlands.
    Vandenberghe, Rik
    Neurology Service, University Hospitals Leuven, Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
    Schaeverbeke, Jolien
    Neurology Service, University Hospitals Leuven, Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
    Gabel, Silvy
    Neurology Service, University Hospitals Leuven, Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
    Popp, Julius
    Old Age Psychiatry, University Hospital Lausanne, Lausanne, Switzerland; Department of Geriatric Psychiatry, Psychiatry University Hospital Zürich, Zürich, Switzerland.
    Peyratout, Gwendoline
    Old Age Psychiatry, University Hospital Lausanne, Lausanne, Switzerland.
    Martinez-Lage, Pablo
    Fundación CITA-Alzhéimer Fundazioa, San Sebastian, Spain.
    Tainta, Mikel
    Fundación CITA-Alzhéimer Fundazioa, San Sebastian, Spain.
    Tsolaki, Magda
    1st Department of Neurology, AHEPA University Hospital, Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, Makedonia, Thessaloniki, Greece.
    Freund-Levi, Yvonne
    Örebro University, School of Medical Sciences. Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; Department of Psychiatry in Region Örebro County, Örebro, Sweden; Department of Old Age Psychiatry, Psychology & Neuroscience, King's College, London, UK.
    Lovestone, Simon
    University of Oxford, Oxford, United Kingdom (currently at Johnson and Johnson Medical Ltd.), London, UK.
    Streffer, Johannes
    Institute Born-Bunge, Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Belgium; UCB Biopharma SPRL, Brain-l'Alleud, Belgium.
    Barkhof, Frederik
    Department of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands; Institutes of Neurology & Healthcare Engineering, UCL London, London, UK .
    Bertram, Lars
    Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany; Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway .
    Blennow, Kaj
    Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
    Zetterberg, Henrik
    Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK; UK Dementia Research Institute at UCL, London, UK.
    Visser, Pieter Jelle
    Department of Psychiatry and Neuropsychology, Alzheimer Centrum Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden.
    Vos, Stephanie J. B.
    Department of Psychiatry and Neuropsychology, Alzheimer Centrum Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
    Cerebrospinal fluid proteomic profiling of individuals with mild cognitive impairment and suspected non-Alzheimer's disease pathophysiology2023In: Alzheimer's & Dementia: Journal of the Alzheimer's Association, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 19, no 3, p. 807-820Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Suspected non-Alzheimer's disease pathophysiology (SNAP) is a biomarker concept that encompasses individuals with neuronal injury but without amyloidosis. We aim to investigate the pathophysiology of SNAP, defined as abnormal tau without amyloidosis, in individuals with mild cognitive impairment (MCI) by cerebrospinal fluid (CSF) proteomics.

    METHODS: Individuals were classified based on CSF amyloid beta (Aβ)1-42 (A) and phosphorylated tau (T), as cognitively normal A-T- (CN), MCI A-T+ (MCI-SNAP), and MCI A+T+ (MCI-AD). Proteomics analyses, Gene Ontology (GO), brain cell expression, and gene expression analyses in brain regions of interest were performed.

    RESULTS: A total of 96 proteins were decreased in MCI-SNAP compared to CN and MCI-AD. These proteins were enriched for extracellular matrix (ECM), hemostasis, immune system, protein processing/degradation, lipids, and synapse. Fifty-one percent were enriched for expression in the choroid plexus.

    CONCLUSION: The pathophysiology of MCI-SNAP (A-T+) is distinct from that of MCI-AD. Our findings highlight the need for a different treatment in MCI-SNAP compared to MCI-AD.

  • 13.
    Eriksdotter, Maria
    et al.
    Department of Neurobiology, Care Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Stockholm; Department of Geriatric Medicine, Karolinska University Hospital, Huddinge, Stockholm.
    Vedin, Inger
    Department of Medicine, Division of Hematology, Karolinska Institutet, Huddinge, Stockholm.
    Falahati, Farshad
    Department of Neurobiology, Care Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Stockholm.
    Freund-Levi, Yvonne
    Department of Neurobiology, Care Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Stockholm.
    Hjorth, Erik
    Department of Neurobiology, Care Sciences and Society (NVS), Division of Neurodegeneration, Karolinska Institutet, Huddinge, Stockholm.
    Faxen-Irving, Gerd
    Department of Neurobiology, Care Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Stockholm.
    Wahlund, Lars-Olof
    Department of Neurobiology, Care Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Stockholm; Department of Geriatric Medicine, Karolinska University Hospital, Huddinge, Stockholm.
    Schultzberg, Marianne
    Department of Neurobiology, Care Sciences and Society (NVS), Division of Neurodegeneration, Karolinska Institutet, Huddinge, Stockholm.
    Basun, Hans
    Division of Geriatrics, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; Department of Geriatric Medicine, Akademiska sjukhuset, Uppsala, Sweden.
    Cederholm, Tommy
    Division of Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; Department of Geriatric Medicine, Akademiska sjukhuset, Uppsala, Sweden.
    Palmblad, Jan
    Department of Medicine, Division of Hematology, Karolinska Institutet, Huddinge, Stockholm.
    Plasma Fatty Acid Profiles in Relation to Cognition and Gender in Alzheimer's Disease Patients During Oral Omega-3 Fatty Acid Supplementation: The OmegAD Study2015In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 48, no 3, p. 805-812Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: ω3 fatty acids (ω3 FAs) may slow the rate of decline in cognitive performance in mild forms of cognitive impairment and Alzheimer's disease (AD). However, the relationship between changes of plasma ω3 FA levels and cognitive performance, as well as effects of gender, are poorly known.

    OBJECTIVE: To study the effect of 6-month administration of DHA-rich ω3 FA supplementation on plasma FA profiles in patients with mild to moderate AD in relation to cognitive performance and gender. This investigation is part of the OmegAD Study.

    METHODS: 174 AD patients (74 ± 9 years) were randomized to a daily intake of 2.3 g ω3 FA or placebo for 6 months; subsequently all received the ω3 FA preparation for the next 6 months. Baseline as well as changes in plasma levels of the main ω3 FAs in 165 patients, while receiving ω3 FA supplementation for 6 months, were analyzed for association to cognitive performance (assessed by ADAS-cog and MMSE scores) as well as to gender.

    RESULTS: Preservation of cognitive functioning, assessed by ADAS-cog or its sub-items (but not MMSE) scores, was significantly associated to increasing plasma ω3 FA levels over time. Thus, the higher ω3 FA plasma levels rose, the lower was the rate of cognitive deterioration. This effect was not related to gender; since although females displayed higher ω3 FA plasma levels than did males after 6 months of supplementation, this difference disappeared when adjusted for body weight.

    CONCLUSIONS: Since our study suggests dose-response relationships between plasma levels of ω3 FA and preservation of cognition, future ω3 FA trials in patients with mild AD should consider exploring graded (and body weight adjusted) doses of ω3 FA.

  • 14.
    Faxen-Irving, Gerd
    et al.
    Department of Neurobiology, Care Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Sweden.
    Falahati, Farshad
    Department of Neurobiology, Care Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Sweden.
    Basun, Hans
    Department of Public Health and Caring Sciences, Division of Geriatrics, Uppsala University, Uppsala, Sweden.
    Eriksdotter, Maria
    Department of Neurobiology, Care Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Sweden; Department of Geriatrics, Karolinska University Hospital, Huddinge, Sweden.
    Vedin, Inger
    Department of Medicine, Division of Hematology, Department of NVS, Karolinska Institutet, Huddinge, Sweden.
    Wahlund, Lars-Olof
    Department of Neurobiology, Care Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Sweden; Department of Geriatrics, Karolinska University Hospital, Huddinge, Sweden.
    Schultzberg, Marianne
    Division of Neurodegeneration, Karolinska Institutet, Huddinge, Sweden.
    Hjorth, Erik
    Division of Neurodegeneration, Karolinska Institutet, Huddinge, Sweden.
    Palmblad, Jan
    Department of Medicine, Division of Hematology, Department of NVS, Karolinska Institutet, Huddinge, Sweden.
    Cederholm, Tommy
    Department of Public Health and Caring Sciences, Division of Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden; Department of Geriatric Medicine, Akademiska sjukhuset, Uppsala, Sweden.
    Freund-Levi, Yvonne
    Department of Neurobiology, Care Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Sweden; Department of Geriatrics, Karolinska University Hospital, Huddinge, Sweden.
    Does Fatty Acid Composition in Subcutaneous Adipose Tissue Differ between Patients with Alzheimer's Disease and Cohabiting Proxies?2018In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 61, no 2, p. 515-519Article in journal (Refereed)
    Abstract [en]

    Low tissue levels of the major marine ω3 fatty acids (FAs) DHA and EPA are found in Alzheimer's disease (AD). We investigated if healthy proxies to AD patients have higher levels of these ω3 FAs. We observed lower levels of EPA and DHA in subcutaneous adipose tissue biopsies from 64 AD patients compared with 16 cognitively healthy proxies. No significant difference was observed when pairwise comparisons were made between a subset of 16 AD patients and their co-habiting proxies. Larger studies are needed to replicate these findings and to determine if they could depend on FA intake or differences in metabolism.

  • 15.
    Faxén-Irving, Gerd
    et al.
    Department of NVS, Section of Clinical Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Freund-Levi, Yvonne
    Department of NVS, Section of Clinical Geriatrics, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Eriksdotter-Jönhagen, Maria
    Department of NVS, Section of Clinical Geriatrics, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Basun, Hans
    Department of Public Health and Caring Sciences, Division of Geriatrics, Uppsala University Hospital, Uppsala, Sweden.
    Hjorth, Erik
    Department of NVS, Section of Clinical Nutrition, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Palmblad, Jan
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Vedin, Inger
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Cederholm, Tommy
    Department of Public Health and Caring Sciences, Division of Clinical Nutrition and Metabolism, Uppsala University Hospital, Uppsala, Sweden.
    Wahlund, Lars-Olof
    Department of NVS, Section of Clinical Geriatrics, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Effects on transthyretin in plasma and cerebrospinal fluid by DHA-rich n - 3 fatty acid supplementation in patients with Alzheimer's disease: the OmegAD study2013In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 36, no 1, p. 1-6Article in journal (Refereed)
    Abstract [en]

    Transthyretin (TTR) binds amyloid-β (Aβ) and may reduce brain Aβ, a pathological feature in Alzheimer's disease (AD). N - 3 fatty acids (FA), docosahexaenoic (DHA), and eicosapentaenoic acid (EPA) may increase TTR transcription in rat hippocampus. We studied effects of n - 3 FA supplementation on TTR-levels in patients with AD. Outpatients were randomized to receive 1.7 g DHA and 0.6 g EPA (n - 3/n - 3 group) or placebo (placebo/n - 3 group) during 6 months. After 6 months, all patients received n - 3 FA for another 6 months. TTR and FA were measured in plasma in all subjects, whereas TTR in cerebrospinal fluid (CSF) was measured in a subgroup. The study was completed by 89 patients in the n - 3/n - 3 group (75 y, 57% w) and 85 in the placebo/n - 3 group (75 y, 46% w). Baseline plasma-TTR was within normal range in both groups. After 6 months, plasma-TTR decreased in the placebo/n - 3 group (p < 0.001 within and p < 0.015 between the groups). No changes were observed in CSF TTR. From 6 to 12 months when both groups were supplemented, plasma-TTR increased significantly in both groups. Repeated measures ANOVA indicated an increase in TTR over time (p = 0.04) in those receiving n - 3 FA for 12 months. By linear regression analyses, n - 3 FA treatment was independently associated with increased plasma-TTR at 6 months (β = -0.172, p = 0.028). Thus, n - 3 FA treatment appeared to increase plasma-TTR in patients with AD. Since TTR may influence Aβ deposition in the brain, the results warrant further exploration.

  • 16.
    Fjellström, Christina
    et al.
    Department of Food, Nutrition and Dietetics, Uppsala University, Uppsala, Sweden.
    Starkenberg, Åsa
    Department of Food, Nutrition and Dietetics, Uppsala University, Uppsala, Sweden.
    Wesslén, Annika
    MEDEA Consultant Bureau, Uppsala, Sweden.
    Tysén Bäckstrom, Ann-Christine
    Department of Geriatrics, Karolinska University Hospital, Huddinge, Sweden.
    Faxén-Irving, Gerd
    Division of Clinical Nutrition, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Huddinge, Sweden; Department of Clinical Nutrition and Dietetics, Karolinska University Hospital, Huddinge, Sweden.
    The OmegAD Study group,
    To Be a Good Food Provider: An Exploratory Study Among Spouses of Persons With Alzheimer's Disease2010In: American Journal of Alzheimer’s Disease and Other Dementia, ISSN 1533-3175, E-ISSN 1938-2731, Vol. 25, no 6, p. 521-526Article in journal (Refereed)
    Abstract [en]

    Large proportions of people with dementia live at home and need help from a relative. The aim of the current study was to examine how people living with persons with Alzheimer's disease (AD) perceived everyday life aspects of food choices, cooking, and food-related work. The analyses are based on focus group interviews including women and men acting as caregivers to people with AD and living in Sweden. The main results identified from the data, were how cohabitants to persons with AD struggle with either taking on a new role as a food provider or extending it, but also how they tried to cope as carer, which entailed food being an important part of the treatment of the disease. Those expressing greatest concern were those perceiving themselves as inexperienced food providers and carers, which in this study were all men.

  • 17.
    Forsberg, Anton
    et al.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Juréus, Anders
    Neuroscience Research & Therapy Area, AstraZeneca Research & Development, Södertälje, Sweden.
    Cselényi, Zsolt
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; AstraZeneca Translational Sciences Centre, PET CoE, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden.
    Eriksdotter, Maria
    Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Freund-Levi, Yvonne
    Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; ; Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Jeppsson, Fredrik
    Neuroscience Research & Therapy Area, AstraZeneca Research & Development, Södertälje, Sweden; Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
    Swahn, Britt-Marie
    Neuroscience Research & Therapy Area, AstraZeneca Research & Development, Södertälje, Sweden.
    Sandell, Johan
    Neuroscience Research & Therapy Area, AstraZeneca Research & Development, Södertälje, Sweden.
    Julin, Per
    Neuroscience Research & Therapy Area, AstraZeneca Research & Development, Södertälje, Sweden.
    Schou, Magnus
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; AstraZeneca Translational Sciences Centre, PET CoE, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden.
    Andersson, Jan
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Johnström, Peter
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; AstraZeneca Translational Sciences Centre, PET CoE, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden.
    Varnäs, Katarina
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Halldin, Christer
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Farde, Lars
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; AstraZeneca Translational Sciences Centre, PET CoE, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden.
    Svensson, Samuel
    Neuroscience Research & Therapy Area, AstraZeneca Research & Development, Södertälje, Sweden.
    Low background and high contrast PET imaging of amyloid-β with [11C]AZD2995 and [11C]AZD2184 in Alzheimer's disease patients2013In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 40, no 4, p. 580-593Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The aim of this study was to evaluate AZD2995 side by side with AZD2184 as novel PET radioligands for imaging of amyloid-β in Alzheimer's disease (AD).

    METHODS: In vitro binding of tritium-labelled AZD2995 and AZD2184 was studied and compared with that of the established amyloid-β PET radioligand PIB. Subsequently, a first-in-human in vivo PET study was performed using [(11)C]AZD2995 and [(11)C]AZD2184 in three healthy control subjects and seven AD patients.

    RESULTS: AZD2995, AZD2184 and PIB were found to share the same binding site to amyloid-β. [(3)H]AZD2995 had the highest signal-to-background ratio in brain tissue from patients with AD as well as in transgenic mice. However, [(11)C]AZD2184 had superior imaging properties in PET, as shown by larger effect sizes comparing binding potential values in cortical regions of AD patients and healthy controls. Nevertheless, probably due to a lower amount of nonspecific binding, the group separation of the distribution volume ratio values of [(11)C]AZD2995 was greater in areas with lower amyloid-β load, e.g. the hippocampus.

    CONCLUSION: Both AZD2995 and AZD2184 detect amyloid-β with high affinity and specificity and also display a lower degree of nonspecific binding than that reported for PIB. Overall [(11)C]AZD2184 seems to be an amyloid-β radioligand with higher uptake and better group separation when compared to [(11)C]AZD2995. However, the very low nonspecific binding of [(11)C]AZD2995 makes this radioligand potentially interesting as a tool to study minute levels of amyloid-β. This sensitivity may be important in investigating, for example, early prodromal stages of AD or in the longitudinal study of a disease modifying therapy.

  • 18.
    Freund-Levi, Yvonne
    et al.
    Department of NVS, Section of Clinical Geriatrics, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Basun, Hans
    Division of Geriatrics, Department of Public Health and Caring Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Cederholm, Tommy
    Clinical Nutrition Research, Department of Public Health and Caring Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Faxén-Irving, Gerd
    Department of NVS, Section of Clinical Geriatrics, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Garlind, Anita
    Department of NVS, Section of Clinical Geriatrics, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Grut, Mikaela
    Department of Geriatrics, Danderyd Hospital, Stockholm, Sweden.
    Vedin, Inger
    Department of Medicine, Division of Hematology, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Palmblad, Jan
    Department of Medicine, Division of Hematology, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Wahlund, Lars-Olof
    Department of NVS, Section of Clinical Geriatrics, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Eriksdotter-Jönhagen, Maria
    Department of NVS, Section of Clinical Geriatrics, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Omega-3 supplementation in mild to moderate Alzheimer's disease: effects on neuropsychiatric symptoms2008In: International Journal of Geriatric Psychiatry, ISSN 0885-6230, E-ISSN 1099-1166, Vol. 23, no 2, p. 161-169Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Epidemiological and animal studies have suggested that dietary fish or fish oil rich in omega-3 fatty acids (omega3), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may have effects in psychiatric and behavioral symptoms in Alzheimer's disease (AD). An association with APOEomega4 carriers and neuropsychiatric symptoms in AD has also been suggested.

    OBJECTIVE: To determine effects of dietary omega3 supplementation to AD patients with mild to moderate disease on psychiatric and behavioral symptoms, daily functions and a possible relation to APOEgenotype.

    METHODS: Randomized, double-blind, placebo-controlled clinical trial where 204 AD patients (74+/-9 years) with acetylcholine esterase inhibitor treatment and a MMSE>15 points were randomized to daily intake of 1.7 g DHA and 0.6 g EPA (omega3 group) or placebo for 6 months. Then, all received the omega3 supplementation for 6 more months. Neuropsychiatric symptoms were measured with Neuropsychiatric Inventory (NPI) and Montgomery Asberg Depression Scale (MADRS). Caregivers burden and activities of daily living (Disability Assessment for Dementia, DAD) were also assessed.

    RESULTS: One hundred and seventy-four patients fulfilled the trial. 72% were APOEomega4 carriers. No significant overall treatment effects on neuropsychiatric symptoms, on activities of daily living or on caregiver's burden were found. However, significant positive treatment effects on the scores in the NPI agitation domain in APOEomega4 carriers (p=0.006) and in MADRS scores in non-APOEomega4 carriers (p=0.005) were found.

    CONCLUSIONS: Supplementation with omega3 in patients with mild to moderate AD did not result in marked effects on neuropsychiatric symptoms except for possible positive effects on depressive symptoms (assessed by MADRS) in non-APOEomega4 carriers and agitation symptoms (assessed by NPI) in APOEomega4 carriers. ClinicalTrials.gov identifier: NCT00211159

  • 19.
    Freund-Levi, Yvonne
    et al.
    Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Bloniecki, Victor
    Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.
    Auestad, Bjørn
    Research Department, Stavanger University Hospital, Stavanger, Norway; Department of Mathematics and Natural Sciences, University of Stavanger, Stavanger, Norway.
    Tysen Bäckström, Ann Christine
    Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Lärksäter, Marie
    Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Aarsland, Dag
    Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Galantamine versus risperidone for agitation in people with dementia: a randomized, twelve-week, single-center study2014In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 38, no 3-4, p. 234-244Article in journal (Refereed)
    Abstract [en]

    AIMS: To examine the effects of galantamine and risperidone on agitation in patients with dementia.

    METHODS: A total of 100 patients with dementia and neuropsychiatric symptoms (mean age ± SD: 78.6 ± 7.5 years; 67% female) were included in this 12-week, randomized, parallel-group, controlled, single-center trial. The participants received galantamine (n = 50; target dose: 24 mg) or risperidone (n = 50; target dose: 1.5 mg) for 12 weeks.

    RESULTS: Both galantamine and risperidone treatment resulted in reduced agitation. However, risperidone showed a significant advantage over galantamine both at week 3 (mean difference in total Cohen-Mansfield Agitation Inventory score: 3.7 points; p = 0.03) and at week 12 (4.3 points; p = 0.01).

    CONCLUSIONS: Agitation improved in both groups, even if the treatment effects were more pronounced in the risperidone group; however, the effects on cognition and other aspects of tolerability were stronger with galantamine.

  • 20.
    Freund-Levi, Yvonne
    et al.
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Eriksdotter-Jönhagen, Maria
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Cederholm, Tommy
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University Hospital, Uppsala, Sweden.
    Basun, Hans
    Division of Geriatrics, Uppsala University Hospital, Uppsala, Sweden.
    Faxén-Irving, Gerd
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Garlind, Anita
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Vedin, Inger
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Vessby, Bengt
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University Hospital, Uppsala, Sweden.
    Wahlund, Lars-Olof
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Palmblad, Jan
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Medicine, M54, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study - A randomized double-blind trial2006In: Archives of Neurology, ISSN 0003-9942, E-ISSN 1538-3687, Vol. 63, no 10, p. 1402-1408Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Epidemiologic and animal studies have suggested that dietary fish or fish oil rich in omega-3 fatty acids, for example, docosahexaenoic acid and eicosapentaenoic acid, may prevent Alzheimer disease (AD).

    OBJECTIVE: To determine effects of dietary omega-3 fatty acid supplementation on cognitive functions in patients with mild to moderate AD.

    DESIGN: Randomized, double-blind, placebo-controlled clinical trial.

    PARTICIPANTS: Two hundred four patients with AD (age range [mean +/- SD], 74 +/- 9 years) whose conditions were stable while receiving acetylcholine esterase inhibitor treatment and who had a Mini-Mental State Examination (MMSE) score of 15 points or more were randomized to daily intake of 1.7 g of docosahexaenoic acid and 0.6 g of eicosapentaenoic acid (omega-3 fatty acid-treated group) or placebo for 6 months, after which all received omega-3 fatty acid supplementation for 6 months more.

    MAIN OUTCOME MEASURES: The primary outcome was cognition measured with the MMSE and the cognitive portion of the Alzheimer Disease Assessment Scale. The secondary outcome was global function as assessed with the Clinical Dementia Rating Scale; safety and tolerability of omega-3 fatty acid supplementation; and blood pressure determinations.

    RESULTS: One hundred seventy-four patients fulfilled the trial. At baseline, mean values for the Clinical Dementia Rating Scale, MMSE, and cognitive portion of the Alzheimer Disease Assessment Scale in the 2 randomized groups were similar. At 6 months, the decline in cognitive functions as assessed by the latter 2 scales did not differ between the groups. However, in a subgroup (n = 32) with very mild cognitive dysfunction (MMSE >27 points), a significant (P<.05) reduction in MMSE decline rate was observed in the omega-3 fatty acid-treated group compared with the placebo group. A similar arrest in decline rate was observed between 6 and 12 months in this placebo subgroup when receiving omega-3 fatty acid supplementation. The omega-3 fatty acid treatment was safe and well tolerated.

    CONCLUSIONS: Administration of omega-3 fatty acid in patients with mild to moderate AD did not delay the rate of cognitive decline according to the MMSE or the cognitive portion of the Alzheimer Disease Assessment Scale. However, positive effects were observed in a small group of patients with very mild AD (MMSE >27 points).

  • 21.
    Freund-Levi, Yvonne
    et al.
    Divisions of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Huddinge, Stockholm.
    Hjorth, Erik
    Divisions of Neurodegeneration, Department of Neurobiology, Care Sciences and Society (NVS), Huddinge, Stockholm.
    Lindberg, Catharina
    Divisions of Neurodegeneration, Department of Neurobiology, Care Sciences and Society (NVS), Huddinge, Stockholm.
    Cederholm, Tommy
    Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Faxen-Irving, Gerd
    Clinical Nutrition, Department of Neurobiology, Care Sciences and Society (NVS), Huddinge, Stockholm.
    Vedin, Inger
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm.
    Palmblad, Jan
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm.
    Wahlund, Lars-Olof
    Divisions of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Huddinge, Stockholm.
    Schultzberg, Marianne
    Divisions of Neurodegeneration, Department of Neurobiology, Care Sciences and Society (NVS), Huddinge, Stockholm.
    Basun, Hans
    Geriatrics, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Eriksdotter Jönhagen, Maria
    Divisions of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Huddinge, Stockholm.
    Effects of omega-3 fatty acids on inflammatory markers in cerebrospinal fluid and plasma in Alzheimer's disease: the OmegAD study2009In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 27, no 5, p. 481-490Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: omega-3 fatty acids (omega-3 FAs) found in dietary fish or fish oils are anti-inflammatory agents that may influence Alzheimer's disease (AD).

    OBJECTIVE: To study the effects of dietary omega-3 FA supplementation on inflammatory markers in cerebrospinal fluid (CSF) and plasma from patients with mild to moderate AD.

    METHODS: Thirty-five patients (70.3 +/- 8.2 years) were randomized to a daily intake of 2.3 g omega-3 FAs or placebo for 6 months. The inflammatory markers interleukin (IL)-6, tumour necrosis factor-alpha and soluble interleukin-1 receptor type II (sIL-1RII) were analysed in CSF and plasma at baseline and at 6 months. The AD markers tau-protein, hyperphosphorylated tau-protein and beta-amyloid (Abeta(1-42)) were assessed in CSF. High-sensitivity C-reactive protein was assessed in plasma. A possible relation to the APOE genotype was investigated.

    RESULTS: There was no significant treatment effect of omega-3 FAs on inflammatory and AD biomarkers in CSF or on inflammatory markers in plasma, nor was there any relation with APOE. A significant correlation was observed at baseline between sIL-1RII and Abeta(1-42) levels in CSF.

    CONCLUSIONS: Treatment of AD patients with omega-3 FAs for 6 months did not influence inflammatory or biomarkers in CSF or plasma. The correlation between sIL-1RII and Abeta(1-42) may reflect the reciprocal interactions between IL-1 and Abeta peptides.

  • 22.
    Freund-Levi, Yvonne
    et al.
    Division of Clinical Geriatrics, Department of Neurobiology, Caring Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Jedenius, Erik
    Division of Clinical Geriatrics, Department of Neurobiology, Caring Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden.
    Tysen-Bäckström, Ann Christine
    Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Lärksäter, Marie
    Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Wahlund, Lars-Olof
    Division of Clinical Geriatrics, Department of Neurobiology, Caring Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Eriksdotter, Maria
    Division of Clinical Geriatrics, Department of Neurobiology, Caring Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Galantamine versus risperidone treatment of neuropsychiatric symptoms in patients with probable dementia: an open randomized trial2014In: The American journal of geriatric psychiatry, ISSN 1064-7481, E-ISSN 1545-7214, Vol. 22, no 4, p. 341-248Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine the effects of galantamine and risperidone on neuropsychiatric symptoms in dementia (NPSD) and global function.

    METHODS: Using a randomized, controlled and open-blind, one-center trial at an in- and outpatient clinic at a university hospital, we studied 100 adults with probable dementia and NPSD. Participants received galantamine (N = 50, target dose 24 mg) or risperidone (N = 50, target dose 1.5 mg) for 12 weeks. The primary outcome was effects on NPSD assessed by the Neuropsychiatric Inventory (NPI). Secondary measures included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating, Clinical Global Impression, and Simpson Angus scales. All tests were performed before and after treatment.

    RESULTS: Outcome measures were analyzed using analysis of covariance. Ninety-one patients (67% women, mean age 79 ± 7.5 years) with initial NPI score of 51.0 (± 25.8) and MMSE of 20.1 (± 4.6) completed the trial. Both galantamine and risperidone treatments resulted in improved NPSD symptoms and were equally effective in treating several NPI domains. However, risperidone showed a significant treatment advantage in the NPI domains irritation and agitation, F(1, 97) = 5.2, p = 0.02. Galantamine treatment also ameliorated cognitive functions where MMSE scores increased 2.8 points compared with baseline (95% confidence interval: 1.96-3.52). No treatment-related severe side effects occurred.

    CONCLUSIONS: These results support that galantamine, with its benign safety profile, can be used as first-line treatment of NPSD symptoms, unless symptoms of irritation and agitation are prominent, where risperidone is more efficient.

  • 23.
    Freund-Levi, Yvonne
    et al.
    Division of Clinical Geriatrics, Department of Neurobiology, Caring Sciences and Society and, Department of Geriatric Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Jedenius, Erik
    Division of Clinical Geriatrics, Department of Neurobiology, Caring Sciences and Society and, Department of Geriatric Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Wahlund, Lars-Olof
    Division of Clinical Geriatrics, Department of Neurobiology, Caring Sciences and Society and, Department of Geriatric Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Eriksdotter, Maria
    Division of Clinical Geriatrics, Department of Neurobiology, Caring Sciences and Society and, Department of Geriatric Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Tysen-Bäckström, Ann Christine
    Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Lärksäter, Marie
    Department of Geriatric Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Response to Bogaiksy's Letter to the Editor2014In: The American journal of geriatric psychiatry, ISSN 1064-7481, E-ISSN 1545-7214, Vol. 22, no 9, p. 951-951Article in journal (Refereed)
    Abstract [en]

    Refers to Michael Bogaisky, Galantamine Versus Risperidone Treatment of Neuropsychiatric Symptoms in Patients with Probable Dementia: An Open Randomized Trial, The American Journal of Geriatric Psychiatry, Volume 22, Issue 9, September 2014, Pages 951.

  • 24.
    Freund-Levi, Yvonne
    et al.
    Karolinska Institute, Stockholm, Sweden.
    Jonhagen, M.E.
    Karolinska Institute, Stockholm, Sweden.
    Wahlund, L.-O.
    Karolinska Institute, Stockholm, Sweden.
    Basun, H
    Dept Geriatrics, Academic Hospital, Uppsala, Sweden.
    Palmblad, J
    Dept Medicine, Karolinska Institute and Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Cederholm, T
    Karolinska Institute, Stockholm, Sweden.
    Safety and tolerability of omega-3 fatty acids in patients with Alzheimer's disease2004In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 25, no Supplement 2, p. S471-S471Article in journal (Other academic)
  • 25.
    Freund-Levi, Yvonne
    et al.
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Vedin, I
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Cederholm, T
    Department of Public Health and Caring Sciences, Uppsala University Hospital, Uppsala, Sweden; Division of Clinical Nutrition and Metabolism, Uppsala University Hospital, Uppsala, Sweden.
    Basun, H
    Department of Public Health and Caring Sciences, Uppsala University Hospital, Uppsala, Sweden; Geriatrics, Uppsala University Hospital, Uppsala, Sweden.
    Faxén Irving, G
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Eriksdotter, M
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Hjorth, E
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Schultzberg, M
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Vessby, B
    Department of Public Health and Caring Sciences, Uppsala University Hospital, Uppsala, Sweden; Geriatrics, Uppsala University Hospital, Uppsala, Sweden.
    Wahlund, L-O
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Salem, N
    National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville MD, United States.
    Palmblad, J
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Transfer of omega-3 fatty acids across the blood-brain barrier after dietary supplementation with a docosahexaenoic acid-rich omega-3 fatty acid preparation in patients with Alzheimer's disease: the OmegAD study2014In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 275, no 4, p. 428-436Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Little is known about the transfer of essential fatty acids (FAs) across the human blood-brain barrier (BBB) in adulthood. In this study, we investigated whether oral supplementation with omega-3 (n-3) FAs would change the FA profile of the cerebrospinal fluid (CSF).

    METHODS: A total of 33 patients (18 receiving the n-3 FA supplement and 15 receiving placebo) were included in the study. These patients were participants in the double-blind, placebo-controlled randomized OmegAD study in which 204 patients with mild Alzheimer's disease (AD) received 2.3 g n-3 FA [high in docosahexaenoic acid (DHA)] or placebo daily for 6 months. CSF FA levels were related to changes in plasma FA and to CSF biomarkers of AD and inflammation.

    RESULTS: At 6 months, the n-3 FA supplement group displayed significant increases in CSF (and plasma) eicosapentaenoic acid (EPA), DHA and total n-3 FA levels (P < 0.01), whereas no changes were observed in the placebo group. Changes in CSF and plasma levels of EPA and n-3 docosapentaenoic acid were strongly correlated, in contrast to those of DHA. Changes in DHA levels in CSF were inversely correlated with CSF levels of total and phosphorylated tau, and directly correlated with soluble interleukin-1 receptor type II. Thus, the more DHA increased in CSF, the greater the change in CSF AD/inflammatory biomarkers.

    CONCLUSIONS: Oral supplementation with n-3 FAs conferred changes in the n-3 FA profile in CSF, suggesting transfer of these FAs across the BBB in adults.

  • 26.
    Freund-Levi, Yvonne
    et al.
    Section of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet and Department of Geriatrics Karolinska University Hospital Stockholm, Sweden.
    Vedin, Inger
    Division of Haematology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
    Hjorth, Erik
    Division of Neurodegeneration, Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden.
    Basun, Hans
    Division of Geriatrics, Uppsala University, Uppsala, Sweden; Chaire d'Excellence Program, Department of Biochemistry, Molecular Biology and Nutrition, Universite d'Auvergne, Clermont-Ferrand, France.
    Faxén Irving, Gerd
    Divisions of Clinical Nutrition, Karolinska Institutet, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
    Schultzberg, Marianne
    Division of Neurodegeneration, Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden.
    Eriksdotter, Maria
    Section of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet and Department of Geriatrics Karolinska University Hospital Stockholm, Sweden.
    Palmblad, Jan
    Division of Haematology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
    Vessby, Bengt
    Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Wahlund, Lars-Olof
    Section of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet and Department of Geriatrics Karolinska University Hospital Stockholm, Sweden.
    Cederholm, Tommy
    Clinical Nutrition and Metabolism, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Basu, Samar
    Division of Oxidative Stress and Inflammation, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; Chaire d'Excellence Program, Department of Biochemistry, Molecular Biology and Nutrition, Universite d'Auvergne, Clermont-Ferrand, France.
    Effects of supplementation with omega-3 fatty acids on oxidative stress and inflammation in patients with Alzheimer's disease: the OmegAD study2014In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 42, no 3, p. 823-831Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Oxidative stress and inflammation are two key mechanisms suggested to be involved in the pathogenesis of Alzheimer's disease (AD). Omega-3 fatty acids (ω-3 FAs) found in fish and fish oil have several biological properties that may be beneficial in AD. However, they may also auto-oxidize and induce in vivo lipid peroxidation.

    OBJECTIVE: The objective of this study was to evaluate systemic oxidative stress and inflammatory biomarkers following oral supplementation of dietary ω-3 FA.

    METHODS: Forty patients with moderate AD were randomized to receive 1.7 g DHA (22:6) and 0.6 g EPA (20:5) or placebo for 6 months. Urinary samples were collected before and after supplementation. The levels of the major F2-isoprostane, 8-iso-PGF2α, a consistent in vivo biomarker of oxidative stress, and 15-keto-dihydro-PGF2α, a major metabolite of PGF2α and biomarker of inflammatory response, were measured.

    RESULTS: F2-isoprostane in urine increased in the placebo group after 6 months, but there was no clear difference in treatment effect between supplemented and non-supplemented patients on the urinary levels of F2-isoprostanes and 15-keto-dihydro-PGF2α. At baseline, the levels of 15-keto-dihydro-PGF2α showed negative correlative relationships to ω-3 FAs, and a positive correlation to linoleic acid. 8-iso-PGF2α correlated negatively to the ω-6 FA arachidonic acid.

    CONCLUSION: The findings indicate that supplementation of ω-3 FAs to patients with AD for 6 months does not have a clear effect on free radical-mediated formation of F2-isoprostane or cyclooxygenase-mediated formation of prostaglandin F2α. The correlative relationships to FAs indicate a potential role of FAs in immunoregulation.

  • 27.
    Funkquist, Anders
    et al.
    Örebro University, School of Medical Sciences. Department of Medicine, Neurology, Halland County Hospital, Halmstad, Sweden.
    Wandt, Birger
    Örebro University Hospital, Örebro, Sweden; School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Blennow, Kaj
    The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Zetterberg, Henrik
    The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK; UK Dementia Research Institute at UCL, London, UK; Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
    Svensson, Johan
    Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Bjellerup, Per
    Department of Clinical Research Center, Västerås, Uppsala University, Uppsala, Sweden; Department of Laboratory Medicine, Central Hospital Västmanland, Västerås, Sweden.
    Freund-Levi, Yvonne
    Department of Neurobiology, Care Sciences and Society Karolinska Institutet, Center for Alzheimer Research Division of Clinical Geriatrics, Stockholm, Sweden; Department of Geriatrics, Örebro University Hospital, Örebro, Sweden; Department of Old Age Psychiatry, Psychology & Neuroscience, King's College, London, UK.
    Sjöberg, Stefan
    Department of Medicine, Karolinska insitutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Medicine, Endocrinology, Halland County Hospital, Halmstad, Sweden; Department of Health Promotion Science, Sophiahemmet University, Stockholm, Sweden.
    Higher CSF/serum free-T4 ratio is associated with improvement of quality of life during treatment with L-thyroxine2023In: Journal of neuroendocrinology, ISSN 0953-8194, E-ISSN 1365-2826, Vol. 35, article id e13272Article in journal (Refereed)
    Abstract [en]

    Up to 20% of individuals with primary hypothyroidism treated with L-thyroxine still suffer from severe symptoms. These are supposedly brain derived and involve both cognitive and emotional domains. Previously, no consistent relationship has been found between thyroid hormones (TH) or TSH levels in blood and quality of life (QoL). Recently, we reported an association between cerebrospinal fluid (CSF)/serum free-thyroxine (f-T4) ratio and QoL, in juvenile hypothyroid patients. Here, we investigated if CSF/serum f-T4 ratio and QoL estimates correlate also during L-thyroxine treatment. Moreover, the CSF biomarker neurogranin (Ng) was used as a biomarker for synaptic function and integrity in clinical research. Ng is partially controlled by TH and therefore we investigated the relationship between QoL parameters and Ng levels. Patients diagnosed with primary hypothyroidism were investigated using vital parameters, serum and CSF analyses of TH, TSH, Ng and QoL questionnaires. Similar procedures were performed after 6 months of treatment. The most marked associations with QoL were found for CSF/serum f-T4 ratio, which was strongly related to several QoL parameters such as the mental subscore of SF-36 (r = 0.83, p < .0005). Ng, which did not differ from that in our healthy controls, was lower in some patients during treatment and higher in others. However, the change in Ng during treatment was significantly correlated with QoL parameters including the mental subscore of SF-36 (r = -0.86, p < .0001). In addition, the CSF/serum f-T4 ratio correlated with the change in Ng (r = -0.75, p = .001). Our results suggest that the ratio between CSF and serum f-T4 is an important biomarker for QoL during treatment of patients with primary hypothyroidism, so far in research, but in the future maybe also in clinical settings. Moreover, this ratio also correlates with the changes in Ng levels during L-thyroxine treatment, further supporting the impact of the TH balance between serum and CSF on QoL.

  • 28.
    Ghafouri, Bijar
    et al.
    Pain and Rehabilitation Centre, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
    Ernberg, Malin
    Department of Dental Medicine, Karolinska Institutet, and the Scandinavian Center for Orofacial Neurosciences (SCON), Karolinska Institute, Stockholm, Sweden.
    Andréll, Paulin
    Region Västra Götaland, Sahlgrenska University Hospital, Östra, department of Anaesthesiology and Intensive Care Medicine, Pain Centre, Sahlgrenska Academy, Gothenburg, Sweden; Department of Anaesthesiology and Intensive Care Medicine, Institute of Clinical Sciences at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Bäckryd, Emmanuel
    Pain and Rehabilitation Centre, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
    Fisher, Marcelo Rivano
    Department of Neurosurgery and Pain Rehabilitation at Skåne University Hospital and Faculty of Medicine Department of Clinical Sciences Malmö, Lund University, Lund, Sweden; Rehabilitation Medicine Research Group, Department of Health Sciences, Lund University, Lund, Sweden.
    Freund-Levi, Yvonne
    Örebro University, School of Medical Sciences. Department of Geriatrics, University Hospital Örebro, Örebro, Sweden; Department of geriatrics, Södertälje Hospital, Södertälje, Sweden; Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Grelz, Henrik
    Department of Neurosurgery and Pain Rehabilitation at Skåne University Hospital and Faculty of Medicine Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
    Gräbel, Olaf
    Region Västra Götaland, Sahlgrenska University Hospital, Östra, department of Anaesthesiology and Intensive Care Medicine, Pain Centre, Sahlgrenska Academy, Gothenburg, Sweden.
    Karlsten, Rolf
    Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University Hospital, Uppsala, Sweden.
    Kosek, Eva
    Department Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Löfgren, Monika
    Department of Clinical Sciences, Karolinska Institutet, and Department of Rehabilitation Medicine, Danderyd Hospital, Stockholm, Sweden.
    Ringqvist, Åsa
    Department of Neurosurgery and Pain Rehabilitation at Skåne University Hospital and Faculty of Medicine Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
    Rudling, Karin
    Department of rehabilitation medicine, University hospital Örebro, Örebro, Sweden.
    Stålnacke, Britt-Marie
    Department of Clinical Sciences, Karolinska Institutet, and Department of Rehabilitation Medicine, Danderyd Hospital, Stockholm, Sweden; Department of Community Medicine and Rehabilitation, Rehabilitation Medicine, Umeå University, Umeå, Sweden.
    Sörlén, Niklas
    Department of Clinical Science, Neurosciences, Umeå University, Umeå, Sweden.
    Uhlin, Karin
    Department of Clinical Sciences, Karolinska Institutet, and Department of Rehabilitation Medicine, Danderyd Hospital, Stockholm, Sweden.
    Westergren, Hans
    Department of Neurosurgery and Pain Rehabilitation at Skåne University Hospital and Faculty of Medicine Department of Clinical Sciences Malmö, Lund University, Lund, Sweden; Rehabilitation Medicine Research Group, Department of Health Sciences, Lund University, Lund, Sweden.
    Gerdle, Björn
    Pain and Rehabilitation Centre, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
    Swedish Chronic Pain Biobank: protocol for a multicentre registry and biomarker project2022In: BMJ Open, E-ISSN 2044-6055, Vol. 12, no 11, article id e066834Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: About 20% of the adult population have chronic pain, often associated with psychological distress, sick leave and poor health. There are large variations in the clinical picture. A biopsychosocial approach is used in investigation and treatment. The concept of personalised medicine, that is, optimising medication types and dosages for individual patients based on biomarkers and other patient-related factors, has received increasing attention in different diseases but used less in chronic pain. This cooperative project from all Swedish University Hospitals will investigate whether there are changes in inflammation and metabolism patterns in saliva and blood in chronic pain patients and whether the changes correlate with clinical characteristics and rehabilitation outcomes.

    METHODS AND ANALYSIS: Patients at multidisciplinary pain centres at University Hospitals in Sweden who have chosen to participate in the Swedish Quality Registry for Pain Rehabilitation and healthy sex-matched and age-matched individuals will be included in the study. Saliva and blood samples will be collected in addition to questionnaire data obtained from the register. From the samples, proteins, lipids, metabolites and micro-RNA will be analysed in relation to, for example, diagnosis, pain characteristics, psychological distress, body weight, pharmacological treatment and clinical rehabilitation results using advanced multivariate data analysis and bioinformatics.

    ETHICS AND DISSEMINATION: The study is approved by the Swedish Ethical Review Authority (Dnr 2021-04929) and will be conducted in accordance with the declaration of Helsinki.The results will be published in open access scientific journals and in popular scientific relevant journals such as those from patient organisations. Data will be also presented in scientific meetings, meeting with healthcare organisations and disseminated in different lecturers at the clinics and universities.

  • 29.
    Hall, Anette
    et al.
    Institute of Clinical Medicine/Neurology, University of Eastern Finland, Kuopio, Finland.
    Mattila, Jussi
    VTT Technical Research Centre of Finland, Tampere, Finland.
    Koikkalainen, Juha
    VTT Technical Research Centre of Finland, Tampere, Finland.
    Lötjonen, Jyrki
    VTT Technical Research Centre of Finland, Tampere, Finland.
    Wolz, Robin
    Biomedical Image Analysis Group, Department of Computing, Imperial College London, London, United Kingdom.
    Scheltens, Philip
    Department of Neurology, Alzheimer Centre, VU University Medical Center, Amsterdam, Netherlands.
    Frisoni, Giovanni
    IRCCS San Giovanni, Laboratory of Epidemiology and Neuroimaging, Brescia, Italy.
    Tsolaki, Magdalini
    Aristotle University of Thessaloniki, Memory and Dementia Centre, 3rd Department of Neurology, "G Papanicolaou" General Hospital, Thessaloniki, Greece.
    Nobili, Flavio
    Clinical Neurology, Department of Neuroscience, Ophthalmology and Genetics, University of Genoa, Genoa, Italy.
    Freund-Levi, Yvonne
    Institution of NVS, Department of Geriatrics, Section of Clinical Geriatrics, Karolinska Institutet, Department of Geriatrics, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Minthon, Lennart
    Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden.
    Frölich, Lutz
    Department of Geriatric Psychiatry, Central Institute of Mental Health, Mannheim, University of Heidelberg, Mannheim, Germany.
    Hampel, Harald
    Sorbonne Universités, Université Pierre et Marie Curie, Institut de la Mémoire et de la Maladie d’Alzheimer & Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris, France.
    Visser, Pieter Jelle
    Department of Neurology, Alzheimer Centre, VU University Medical Center, Amsterdam, Netherlands; Department of Psychiatry and Neuropsychology, University of Maastricht, Maastricht, Netherlands.
    Soininen, Hilkka
    Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland; Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
    Predicting progression from cognitive impairment to Alzheimer's disease with the Disease State Index2015In: Current Alzheimer Research, ISSN 1567-2050, E-ISSN 1875-5828, Vol. 12, no 1, p. 69-79Article in journal (Refereed)
    Abstract [en]

    We evaluated the performance of the Disease State Index (DSI) method when predicting progression to Alzheimer's disease (AD) in patients with subjective cognitive impairment (SCI), amnestic or non-amnestic mild cognitive impairment (aMCI, naMCI). The DSI model measures patients' similarity to diagnosed cases based on available data, such as cognitive tests, the APOE genotype, CSF biomarkers and MRI. We applied the DSI model to data from the DESCRIPA cohort, where non-demented patients (N=775) with different subtypes of cognitive impairment were followed for 1 to 5 years. Classification accuracies for the subgroups were calculated with the DSI using leave-one-out crossvalidation. The DSI's classification accuracy in predicting progression to AD was 0.75 (AUC=0.83) in the total population, 0.70 (AUC=0.77) for aMCI and 0.71 (AUC=0.76) for naMCI. For a subset of approximately half of the patients with high or low DSI values, accuracy reached 0.86 (all), 0.78 (aMCI), and 0.85 (naMCI). For patients with MRI or CSF biomarker data available, theywere 0.78 (all), 0.76 (aMCI) and 0.76 (naMCI), while for clear cases the accuracies rose to 0.90 (all), 0.83 (aMCI) and 0.91 (naMCI). The results show that the DSI model can distinguish between clear and ambiguous cases, assess the severity of the disease and also provide information on the effectiveness of different biomarkers. While a specific test or biomarker may confound analysis for an individual patient, combining several different types of tests and biomarkers could be able to reveal the trajectory of the disease and improve the prediction of AD progression.

  • 30.
    Handels, Ron L. H.
    et al.
    Department of Psychiatry and Neuropsychology, Alzheimer Centre Limburg, School for Mental Health and Neurosciences, Maastricht University, Maastricht, The Netherlands.
    Vos, Stephanie J. B.
    Department of Psychiatry and Neuropsychology, Alzheimer Centre Limburg, School for Mental Health and Neurosciences, Maastricht University, Maastricht, The Netherlands.
    Kramberger, Milica G.
    Department of Neurology, Ljubljana University Medical Centre, Ljubljana, Slovenia.
    Jelic, Vesna
    Division of Clinical Geriatrics, Department of NVS, Karolinska Institutet, Center for Alzheimer Research, Division of Neurogeriatrics, Huddinge, Sweden.
    Blennow, Kaj
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
    van Buchem, Mark
    Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands.
    van der Flier, Wiesje
    Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands; Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
    Freund-Levi, Yvonne
    Division of Clinical Geriatrics, Department of NVS, Karolinska Institutet, Center for Alzheimer Research, Division of Neurogeriatrics, Huddinge, Sweden; Department of Psychiatry, Tiohundra AB Norrtälje Hospital, Stockholm Sweden.
    Hampel, Harald
    AXA Research Fund & UPMC Chair, Paris, France; Sorbonne Universités Pierre et Marie Curie (UPMC) Paris 06, Inserm, CNRS, Institut du cerveau et de la moelle (ICM), Département de Neurologie, Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Hôpital Pitié-Salpêtrière, Paris, France.
    Olde Rikkert, Marcel
    Department of Geriatrics, Radboudumc Alzheimer Centre, Donders Institute for Brain Cognition and Behavior, Radboud University Medical Centre, Nijmegen, The Netherlands.
    Oleksik, Ania
    Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands.
    Pirtosek, Zvezdan
    Department of Neurology, Ljubljana University Medical Centre, Ljubljana, Slovenia.
    Scheltens, Philip
    Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
    Soininen, Hilkka
    Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Neurocenter–Neurology, Kuopio University Hospital, Kuopio, Finland.
    Teunissen, Charlotte
    Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, VU University Medical Centre, Amsterdam, The Netherlands.
    Tsolaki, Magda
    Memory and Dementia Outpatient Clinic, 3rd Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
    Wallin, Asa K.
    Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Winblad, Bengt
    Division of Clinical Geriatrics, Department of NVS, Karolinska Institutet, Center for Alzheimer Research, Division of Neurogeriatrics, Huddinge, Sweden.
    Verhey, Frans R. J.
    Department of Psychiatry and Neuropsychology, Alzheimer Centre Limburg, School for Mental Health and Neurosciences, Maastricht University, Maastricht, The Netherlands.
    Visser, Pieter Jelle
    Department of Psychiatry and Neuropsychology, Alzheimer Centre Limburg, School for Mental Health and Neurosciences, Maastricht University, Maastricht, The Netherlands; Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
    Predicting progression to dementia in persons with mild cognitive impairment using cerebrospinal fluid markers2017In: Alzheimer's & Dementia: Journal of the Alzheimer's Association, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 13, no 8, p. 903-912Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: We aimed to determine the added value of cerebrospinal fluid (CSF) to clinical and imaging tests to predict progression from mild cognitive impairment (MCI) to any type of dementia.

    METHODS: The risk of progression to dementia was estimated using two logistic regression models based on 250 MCI participants: the first included standard clinical measures (demographic, clinical, and imaging test information) without CSF biomarkers, and the second included standard clinical measures with CSF biomarkers.

    RESULTS: Adding CSF improved predictive accuracy with 0.11 (scale from 0-1). Of all participants, 136 (54%) had a change in risk score of 0.10 or higher (which was considered clinically relevant), of whom in 101, it was in agreement with their dementia status at follow-up.

    DISCUSSION: An individual person's risk of progression from MCI to dementia can be improved by relying on CSF biomarkers in addition to recommended clinical and imaging tests for usual care.

  • 31.
    Hjorth, Erik
    et al.
    Department of Neurobiology, Care Sciences and Society, Division of Neurodegeneration, Karolinska Institutet, Stockholm, Sweden.
    Freund-Levi, Yvonne
    Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Immunomodulation of microglia by docosahexaenoic acid and eicosapentaenoic acid.2012In: Current opinion in clinical nutrition and metabolic care, ISSN 1363-1950, E-ISSN 1473-6519, Vol. 15, no 2, p. 134-143Article, review/survey (Refereed)
    Abstract [en]

    PURPOSE OF REVIEW: The omega-3 fatty acids (ω-3 FAs) docosahexaenoic acid and eicosapentaenoic acid are dietary components which have been ascribed many different health benefits. Inflammation is present in, and contributes to, pathological conditions in the central nervous system (CNS). Microglia are the primary cells with immune function in the CNS, and inflammation mediated by activated microglia is present in pathological conditions. In this review, we present and discuss findings on the modulation of microglial activities by ω-3 FAs in vivo as well as in vitro, and propose mechanisms for their effects.

    RECENT FINDINGS: The majority of studies show that ω-3 FAs have anti-inflammatory effects on microglia. However, phagocytosis is an activity associated with inflammation and is increased by ω-3 FAs. This can be understood in the light of recent research on the resolution of inflammation. Resolution is induced by proresolving factors, which are metabolites of ω-3 FAs. Proresolving factors are anti-inflammatory and have been shown to increase phagocytosis. Other mechanisms of the anti-inflammatory actions of ω-3 FAs involve the peroxisome proliferator-activated receptor-γ, ω-3 FA incorporation into the cell membrane, and inhibition of ion currents.

    SUMMARY: Immunomodulation by ω-3 FAs is mediated by several pathways that are interconnected and is a potential therapy for disorders in the CNS.

  • 32.
    Hjorth, Erik
    et al.
    Division of Neurodegeneration, Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden.
    Zhu, Mingqin
    Division of Neurodegeneration, Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden.
    Toro, Veronica Cortés
    Division of Neurodegeneration, Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden.
    Vedin, Inger
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Palmblad, Jan
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Cederholm, Tommy
    Division of Clinical Nutrition and Metabolism, Department of Public Health & Caring Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Freund-Levi, Yvonne
    Clinical Geriatrics, Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden.
    Faxen-Irving, Gerd
    Nutrition, Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden.
    Wahlund, Lars-Olof
    Clinical Geriatrics, Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden.
    Basun, Hans
    Division of Geriatrics, Department of Public Health & Caring Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Eriksdotter, Maria
    Clinical Geriatrics, Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden.
    Schultzberg, Marianne
    Division of Neurodegeneration, Department of Neurobiology, Care Sciences & Society, Karolinska Institutet, Stockholm, Sweden.
    Omega-3 fatty acids enhance phagocytosis of Alzheimer's disease-related amyloid-β42 by human microglia and decrease inflammatory markers2013In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 35, no 4, p. 697-713Article in journal (Refereed)
    Abstract [en]

    The use of supplements with omega-3 (ω3) fatty acids (FAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is widespread due to proposed beneficial effects on the nervous and cardiovascular systems. Many effects of ω3 FAs are believed to be caused by down-regulation and resolution of inflammation. Alzheimer's disease (AD) is associated with inflammation mediated by microglia and astrocytes, and ω3 FAs have been proposed as potential treatments for AD. The focus of the present study is on the effects of DHA and EPA on microglial phagocytosis of the AD pathogen amyloid-β (Aβ), on secreted and cellular markers of immune activity, and on production of brain-derived neurotrophic factor (BDNF). Human CHME3 microglial cells were exposed to DHA or EPA, with or without the presence of Aβ42. Phagocytosis of Aβ42 was analyzed by flow cytometry in conjunction with immunocytochemistry using antibodies to cellular proteins. Secreted proteins were analyzed by ELISA. Both DHA and EPA were found to stimulate microglial phagocytosis of Aβ42. Phagocytosis of Aβ42 was performed by microglia with a predominance of M2 markers. EPA increased the levels of BDNF in the culture medium. The levels of TNF-α were decreased by DHA. Both DHA and EPA decreased the pro-inflammatory M1 markers CD40 and CD86, and DHA had a stimulatory effect on the anti-inflammatory M2 marker CD206. DHA and EPA can be beneficial in AD by enhancing removal of Aβ42, increasing neurotrophin production, decreasing pro-inflammatory cytokine production, and by inducing a shift in phenotype away from pro-inflammatory M1 activation.

  • 33.
    Holmgren, Simon
    et al.
    Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Thomas
    Department of Neurophysiology, Karolinska University Hospital, Huddinge, Sweden .
    Berglund, Anders
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm .
    Aarsland, Dag
    Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; Institute of Psychiatry, Psychology and Neuroscience, Division of Old Age Psychiatry, Kings College, London, UK; Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
    Cummings, Jeffrey
    Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Science, University of Nevada, Las Vegas, USA.
    Freund-Levi, Yvonne
    Örebro University, School of Medical Sciences. Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; Institute of Psychiatry, Psychology and Neuroscience, Division of Old Age Psychiatry, Kings College, London, UK; Department of Psychiatry and Geriatrics, University Hospital Örebro, Sweden .
    Neuropsychiatric Symptoms in Dementia: Considering a Clinical Role for Electroencephalography2022In: The Journal of Neuropsychiatry and Clinical Neurosciences, ISSN 0895-0172, E-ISSN 1545-7222, Vol. 34, no 3, p. 214-223Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Degenerative dementia is characterized by progressive cognitive decline and neuropsychiatric symptoms. People with Alzheimer's disease (AD), the most common cause of dementia, show synaptic loss and disruption of functional brain networks along with neuritic plaques and neurofibrillary tangles. Electroencephalography (EEG) directly reflects synaptic activity, and among patients with AD it is associated with slowing of background activity. The purpose of this study was to identify associations between neuropsychiatric symptoms and EEG in patients with dementia and to determine whether EEG parameters could be used for clinical assessment of pharmacological treatment of neuropsychiatric symptoms in dementia (NPSD) with galantamine or risperidone.

    METHODS: Seventy-two patients with EEG recordings and a score ≥10 on the Neuropsychiatric Inventory (NPI) were included. Clinical assessments included administration of the NPI, the Mini-Mental State Examination (MMSE), and the Cohen-Mansfield Agitation Inventory (CMAI). Patients underwent EEG examinations at baseline and after 12 weeks of treatment with galantamine or risperidone. EEG frequency analysis was performed. Correlations between EEG and assessment scale scores were statistically examined, as were EEG changes from baseline to the week 12 visit and the relationship with NPI, CMAI, and MMSE scores.

    RESULTS: Significant correlations were found between NPI agitation and delta EEG frequencies at baseline and week 12. No other consistent and significant relationships were observed between NPSD and EEG at baseline, after NPSD treatment, or in the change in EEG from baseline to follow-up.

    CONCLUSIONS: The limited informative findings in this study suggest that there exists a complex relationship between NPSD and EEG; hence, it is difficult to evaluate and use EEG for clinical assessment of pharmacological NPSD treatment.

  • 34.
    Holmgren, Simon
    et al.
    Department of Neurobiology, Care Sciences & Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.
    Hjorth, Erik
    Department of Neurobiology, Care Sciences & Society (NVS), Division of Neurodegeneration, Karolinska Institutet, Stockholm, Sweden.
    Schultzberg, Marianne
    Department of Neurobiology, Care Sciences & Society (NVS), Division of Neurodegeneration, Karolinska Institutet, Stockholm, Sweden.
    Lärksäter, Marie
    Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Frenkel, Dan
    Department of Neurobiology, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
    Tysen-Bäckström, Ann Christine
    Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Aarsland, Dag
    Department of Neurobiology, Care Sciences & Society (NVS), Division of Alzheimer’s Disease Research Centre, Karolinska Institutet, Stockholm, Sweden; Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
    Freund-Levi, Yvonne
    Department of Neurobiology, Care Sciences & Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Neuropsychiatric symptoms in dementia: a role for neuroinflammation?2014In: Brain Research Bulletin, ISSN 0361-9230, E-ISSN 1873-2747, Vol. 108, p. 88-93, article id S0361-9230(14)00136-1Article in journal (Refereed)
    Abstract [en]

    Dementia is characterized by a progressive cognitive decline and neuropsychiatric symptoms (NPSD) such as agitation, apathy and sleeping problems. There is some evidence of activation of inflammatory pathways in the brain in dementia, but little research has been performed regarding the role of neuroinflammation in NPSD, which might represent a potential novel target for treatment. The aim of this study was to examine the possible association between NPSD and cerebrospinal fluid (CSF) levels of the cytokines IL-6, TNF-α and IL-10, and the cytokine receptor sIL-1RII, in patients with dementia and NPSD. Ninety-four patients (mean age 79±8; 67% female) with a score on the neuropsychiatric inventory (NPI) ≥10 points, were included. Clinical assessment included administration of NPI, the mini-mental state examination (MMSE) and the Cohen-Mansfield agitation inventory (CMAI). The cytokine levels in CSF samples were analysed by enzyme-linked immunosorbent assay. Correlations were statistically examined using Spearman's rank correlation coefficient (r), and simple- and multiple-linear regression. The anti-inflammatory cytokine IL-10 showed reverse correlations with total NPI score (NPI-total=-0.001, t(90)= 8.50, p=0.004) and NPI sub-items agitation (agitation=-0.007, t(90)=7.02, p=0.009) and night-time behaviour (night time behaviour=-0.006, t(90)=6.34, p=0.01). There was a trend towards reverse correlation between IL-10 and depression (depression=-0.004, t(90)=2.96, p=0.09). Also, the soluble cytokine receptor sIL-1RII showed a trend towards correlation with apathy (apathy=0.82, t(82)=3.62, p=0.06). The levels of IL-6 showed no significant correlations with NPSD. Levels of TNF-α were non-detectable. In Alzheimer's disease (AD) subjects (n=33), IL-6 showed reverse correlation with anxiety (r=-0.35, p=0.049). In mixed AD subjects (n=26), IL-10 showed reverse correlations with the total NPI score (r=-0.46, p=0.02) and depression (r=-0.45, p=0.02). The findings indicate a relationship between neuroinflammation and neuropsychiatric symptoms in AD in which anti-inflammatory signalling by IL-10 is beneficial from a mental health perspective.

  • 35.
    Irving, Gerd Faxén
    et al.
    Clinical Nutrition, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm.
    Freund-Levi, Yvonne
    Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm.
    Erratum: Omega-3 fatty acid supplementation effects on weight and appetite in patients with Alzheimer's disease: The omega-3 Alzheimer's disease study (Journal of the American Geriatrics Society (2009) 57 (11-17))2009In: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 57, no 3, p. 579-579Article in journal (Other academic)
  • 36.
    Irving, Gerd Faxén
    et al.
    Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Freund-Levi, Yvonne
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Eriksdotter-Jönhagen, Maria
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Basun, Hans
    Divisions of Geriatrics, Uppsala University Hospital, Uppsala, Sweden.
    Brismar, Kerstin
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Hjorth, Erik
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Palmblad, Jan
    Department of Medicine, Karolinska University, Hospital, Huddinge, Stockholm, Sweden.
    Vessby, Bengt
    Department of Public Health and Caring Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Vedin, Inger
    Department of Medicine, Karolinska University, Hospital, Huddinge, Stockholm, Sweden.
    Wahlund, Lars-Olof
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Cederholm, Tommy
    Department of Medicine, Karolinska University, Hospital, Huddinge, Stockholm, Sweden.
    Omega-3 fatty acid supplementation effects on weight and appetite in patients with Alzheimer's disease: the omega-3 Alzheimer's disease study2009In: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 57, no 1, p. 11-17Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To study the effects of omega (Omega)-3 fatty acid (FA) supplements on weight and appetite in patients with mild to moderate Alzheimer's disease (AD) in relation to inflammatory biomarkers and apolipoprotein E epsilon4 (APOEepsilon4).

    DESIGN: Randomized, double-blind, placebo-controlled trial.

    SETTING: Specialist memory clinics in the Stockholm catchment area.

    PARTICIPANTS: Two hundred four patients (aged 73+/-9, 52% women) with mild to moderate AD.

    INTERVENTION: Patients with AD received 1.7 g of docosahexaenoic acid (DHA) and 0.6 g of eicosapentaenoic acid (EPA) (Omega-3/Omega-3 group; n=89, aged 73+/-9, 57% women) or placebo 0.6 g of linoleic acid per day (placebo/Omega-3 group; n=85, aged 73+/-9, 46% women) for 6 months. After 6 months, all patients received DHA and EPA for another 6 months.

    MEASUREMENTS: Anthropometry, biochemical nutritional and inflammatory markers, and appetite assessed by caregiver.

    RESULTS: Mean weight and body mass index (kg/m(2)) at baseline were 70.0+/-11.8 kg and 24.3+/-3.0 kg/m(2), respectively. At 6- and 12-month follow-up, weight had increased 0.7+/-2.5 kg (P=.02) and 1.4+/-2.9 kg (P<.001) in the Omega-3/Omega-3 group. In the placebo group, weight was unchanged at 6 months but had increased (P=.01) at 12 months follow-up after Omega-3 supplementation was initiated. Appetite improved in the Omega-3/Omega-3 group over the treatment period (P=.01). In logistic regression analyses, not carrying the APOEepsilon4 allele and high plasma DHA concentrations were independently related to weight gain in the combined group of patients at 6 months follow-up.

    CONCLUSION: A DHA-enriched Omega-3 FA supplement may positively affect weight and appetite in patients with mild to moderate AD. Not carrying the APOEepsilon4 allele and high DHA were independently associated with weight gain.

  • 37.
    Jansen, Willemijn J.
    et al.
    Alzheimer Centre Limburg, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands; Banner Alzheimer's Institute, Phoenix, Arizona, USA.
    Janssen, Olin
    Alzheimer Centre Limburg, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
    Tijms, Betty M.
    Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam University Medical Center (UMC), Amsterdam, the Netherlands.
    Vos, Stephanie J. B.
    Alzheimer Centre Limburg, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
    Ossenkoppele, Rik
    Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam University Medical Center (UMC), Amsterdam, the Netherlands; Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden.
    Visser, Pieter Jelle
    Alzheimer Centre Limburg, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam University Medical Center (UMC), Amsterdam, the Netherlands; Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden .
    Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum2022In: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 79, no 3, p. 228-243Article in journal (Refereed)
    Abstract [en]

    Importance: One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.

    Objective: To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.

    Design, Setting, and Participants: This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.

    Exposures: Alzheimer disease biomarkers detected on PET or in CSF.

    Main Outcomes and Measures: Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.

    Results: Among the 19 097 participants (mean [SD] age, 69.1 [9.8] years; 10 148 women [53.1%]) included, 10 139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P = .04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P = .004), subjective cognitive decline (9%; 95% CI, 3%-15%; P = .005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P = .004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P = .18).

    Conclusions and Relevance: This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.

  • 38.
    Jansen, Willemijn J.
    et al.
    Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
    Ossenkoppele, Rik
    Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands; Department of Radiology and Nuclear Medicine, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands; Department of Neurology, Memory and Aging Center, University of California, San Francisco; Helen Wills Neuroscience Institute, University of California, Berkeley.
    Knol, Dirk L.
    Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands.
    Tijms, Betty M.
    Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
    Scheltens, Philip
    Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
    Verhey, Frans R. J.
    Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
    Visser, Pieter Jelle
    Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands; Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
    Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis2015In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 313, no 19, p. 1924-1938Article in journal (Refereed)
    Abstract [en]

    Importance  Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.

    Objective  To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as measured with biomarkers in participants with normal cognition, subjective cognitive impairment (SCI), or mild cognitive impairment (MCI).

    Data Sources  Relevant biomarker studies identified by searching studies published before April 2015 using the MEDLINE and Web of Science databases and through personal communication with investigators.

    Study Selection  Studies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity.

    Data Extraction and Synthesis  Individual records were provided for 2914 participants with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from 55 studies.

    Main Outcomes and Measures  Prevalence of amyloid pathology on positron emission tomography or in cerebrospinal fluid according to AD risk factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by generalized estimating equations.

    Results  The prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI. APOE-ε4 carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age at which 15% of the participants with normal cognition were amyloid positive was approximately 40 years for APOE ε4ε4 carriers, 50 years for ε2ε4 carriers, 55 years for ε3ε4 carriers, 65 years for ε3ε3 carriers, and 95 years for ε2ε3 carriers. Amyloid positivity was more common in highly educated participants but not associated with sex or biomarker modality.

    Conclusions and Relevance  Among persons without dementia, the prevalence of cerebral amyloid pathology as determined by positron emission tomography or cerebrospinal fluid findings was associated with age, APOE genotype, and presence of cognitive impairment. These findings suggest a 20- to 30-year interval between first development of amyloid positivity and onset of dementia.

  • 39.
    Jansen, Willemijn J.
    et al.
    Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
    Visser, Pieter Jelle
    Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands; Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
    Amyloid Biomarker Study Group,
    Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia2018In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 75, no 1, p. 84-95Article in journal (Refereed)
    Abstract [en]

    Importance: Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.

    Objective: To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.

    Design, Setting, and Participants: This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.

    Main Outcomes and Measures: Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.

    Results: Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P = .16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P < .001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P < .001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.

    Conclusions and Relevance: Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.

  • 40.
    Janssen, Olin
    et al.
    Alzheimer Centre Limburg, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
    Freund-Levi, Yvonne
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Visser, Pieter Jelle
    Alzheimer Centre Limburg, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands; Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden .
    Characteristics of subjective cognitive decline associated with amyloid positivity2021In: Alzheimer's & Dementia: Journal of the Alzheimer's Association, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 18, no 10, p. 1832-1845Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The evidence for characteristics of persons with subjective cognitive decline (SCD) associated with amyloid positivity is limited.

    METHODS: In 1640 persons with SCD from 20 Amyloid Biomarker Study cohort, we investigated the associations of SCD-specific characteristics (informant confirmation, domain-specific complaints, concerns, feelings of worse performance) demographics, setting, apolipoprotein E gene (APOE) ε4 carriership, and neuropsychiatric symptoms with amyloid positivity.

    RESULTS: Between cohorts, amyloid positivity in 70-year-olds varied from 10% to 76%. Only older age, clinical setting, and APOE ε4 carriership showed univariate associations with increased amyloid positivity. After adjusting for these, lower education was also associated with increased amyloid positivity. Only within a research setting, informant-confirmed complaints, memory complaints, attention/concentration complaints, and no depressive symptoms were associated with increased amyloid positivity. Feelings of worse performance were associated with less amyloid positivity at younger ages and more at older ages.

    DISCUSSION: Next to age, setting, and APOE ε4 carriership, SCD-specific characteristics may facilitate the identification of amyloid-positive individuals.

  • 41.
    Jernerén, Fredrik
    et al.
    Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
    Cederholm, Tommy
    Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; Theme Ageing, Karolinska University Hospital, Stockholm, Sweden.
    Refsum, Helga
    Department of Nutrition, University of Oslo, Oslo, Norway; Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
    Smith, A. David
    Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
    Turner, Cheryl
    Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
    Palmblad, Jan
    Departments of Medicine and Hematology, Karolinska University Hospital Huddinge, and the Karolinska Institutet, Stockholm, Sweden.
    Eriksdotter, Maria
    Theme Ageing, Karolinska University Hospital, Stockholm, Sweden; Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Hjorth, Erik
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Faxen-Irving, Gerd
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Wahlund, Lars-Olof
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Schultzberg, Marianne
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Basun, Hans
    Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Freund-Levi, Yvonne
    Örebro University, School of Medical Sciences. Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden; Center for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Sweden; Department of Psychiatry in Region Örebro County and School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro; Department of Old Age Psychiatry, Psychology & Neuroscience, King’s College, London, UK.
    Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer's Disease: The OmegAD Study2019In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 69, no 1, p. 189-197Article in journal (Refereed)
    Abstract [en]

    Background: Trials of supplementation with omega-3 fatty acids (omega 3-FAs) in patients with mild cognitive impairment or Alzheimer's disease (AD) have produced inconsistent effects on cognitive decline. There is evidence of an interaction between B vitamin status and omega 3-FAs in relation to brain atrophy and cognitive decline.

    Objective: We investigated whether baseline levels of plasma total homocysteine (tHcy), a marker of B vitamin status, modify the effects of omega 3-FAs supplementation on cognitive performance in moderate AD.

    Methods: This post hoc analysis of the OmegAD trial included 171 community-based patients with AD (MMSE >= 15): 88 patients received daily doses of 1.7 g docosahexaenoic acid and 0.6 g eicosapentaenoic acid for 6 months. Treatment outcome on cognition was analyzed according to baseline levels of tHcy using a general linear model and ANCOVA.

    Results: We found significant interactions between omega 3-FA supplementation and tHcy on cognition and clinical stage assessed by MMSE (p = 0.040), global CDR (p = 0.059), and CDRsob (p = 0.023), but not on ADAS-cog (p = 0.649). In patients with tHcy levels <11.7 mu mol/L, omega 3-FA supplementation improved cognitive performance as measured by MMSE (+7.1%, 95% CI: 0.59 to 13.7%, p = 0.033) and clinical status as measured by CDRsob (-22.3%, 95% CI: -5.8 to -38.7%, p = 0.009) compared with placebo.

    Conclusion: The effect of omega 3-FA supplementation on MMSE and CDR appears to be influenced by baseline tHcy, suggesting that adequate B vitamin status is required to obtain beneficial effects of omega 3-FA on cognition.

  • 42.
    Karimi, Mohsen
    et al.
    Department of Medicine and Hematology (HERM), Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Vedin, Inger
    Department of Medicine and Hematology (HERM), Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Freund-Levi, Yvonne
    Department of Neurobiology, Care, Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Basun, Hans
    Department of Public Health and Caring Sciences, Division of Geriatrics, Uppsala University Hospital, Uppsala, Sweden.
    Faxén Irving, Gerd
    Department of Neurobiology, Care, Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Eriksdotter, Maria
    Department of Neurobiology, Care, Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Wahlund, Lars-Olof
    Department of Neurobiology, Care, Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Schultzberg, Marianne
    Department of Neurobiology, Care, Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Hjorth, Erik
    Department of Neurobiology, Care, Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Cederholm, Tommy
    Department of Clinical Nutrition and Metabolism, Uppsala University Hospital, Uppsala, Sweden.
    Palmblad, Jan
    Department of Medicine and Hematology (HERM), Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    DHA-rich n-3 fatty acid supplementation decreases DNA methylation in blood leukocytes: the OmegAD study2017In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 106, no 4, p. 1157-1165Article in journal (Refereed)
    Abstract [en]

    Background: Dietary fish oils, rich in long-chain n-3 (ω-3) fatty acids (FAs) [e.g., docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3)], modulate inflammatory reactions through various mechanisms, including gene expression, which is measured as messenger RNA concentration. However, the effects of long-term treatment of humans with DHA and EPA on various epigenetic factors-such as DNA methylation, which controls messenger RNA generation-are poorly described.

    Objective: We wanted to determine the effects of 6 mo of dietary supplementation with an n-3 FA preparation rich in DHA on global DNA methylation of peripheral blood leukocytes (PBLs) and the relation to plasma EPA and DHA concentrations in Alzheimer disease (AD) patients.

    Design: In the present study, DNA methylation in four 5'-cytosine-phosphate-guanine-3' (CpG) sites of long interspersed nuclear element-1 repetitive sequences was assessed in a group of 63 patients (30 given the n-3 FA preparation and 33 given placebo) as an estimation of the global DNA methylation in blood cells. Patients originated from the randomized, double-blind, placebo-controlled OmegAD study, in which 174 AD patients received either 1.7 g DHA and 0.6 g EPA (the n-3 FA group) or placebo daily for 6 mo.

    Results: At 6 mo, the n-3 FA group displayed marked increases in DHA and EPA plasma concentrations (2.6- and 3.5-fold), as well as decreased methylation in 2 out of 4 CpG sites (P < 0.05 for all), respectively. This hypomethylation in CpG2 and CpG4 sites showed a reverse correlation to changes in plasma EPA concentration (r = -0.25, P = 0.045; and r = -0.26, P = 0.041, respectively), but not to changes in plasma DHA concentration, and were not related to apolipoprotein E-4 allele frequency.

    Conclusion: Supplementation with n-3 FA for 6 mo was associated with global DNA hypomethylation in PBLs. Our data may be of importance in measuring various effects of marine oils, including gene expression, in patients with AD and in other patients taking n-3 FA supplements. This trial was registered at clinicaltrials.gov as NCT00211159.

  • 43.
    Kim, Min
    et al.
    Institute of Pharmaceutical Science, King's College London, London, UK; Steno Diabetes Center Copenhagen, Gentofte, Denmark.
    Snowden, Stuart
    Institute of Pharmaceutical Science, King's College London, London, UK; Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Biochemistry, University of Cambridge, Cambridge, UK.
    Suvitaival, Tommi
    Steno Diabetes Center Copenhagen, Gentofte, Denmark.
    Ali, Ashfaq
    Steno Diabetes Center Copenhagen, Gentofte, Denmark.
    Merkler, David J
    Department of Chemistry, University of South Florida, Tampa, FL, USA.
    Ahmad, Tahmina
    Institute of Pharmaceutical Science, King's College London, London, UK.
    Westwood, Sarah
    Department of Psychiatry, University of Oxford, Oxford, UK.
    Baird, Alison
    Department of Psychiatry, University of Oxford, Oxford, UK.
    Proitsi, Petroula
    Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.
    Nevado-Holgado, Alejo
    Department of Psychiatry, University of Oxford, Oxford, UK.
    Hye, Abdul
    Steno Diabetes Center Copenhagen, Gentofte, Denmark.
    Bos, Isabelle
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, The Netherlands.
    Vos, Stephanie
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, The Netherlands.
    Vandenberghe, Rik
    University Hospital Leuven, Leuven, Belgium.
    Teunissen, Charlotte
    Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam University Medical Centers, Amsterdam Neuroscience, Amsterdam, The Netherlands.
    Ten Kate, Mara
    Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam University Medical Centers, Amsterdam Neuroscience, Amsterdam, The Netherlands.
    Scheltens, Philip
    Department of Neurology, Alzheimer Center, Amsterdam University Medical Centers, Amsterdam, The Netherlands.
    Gabel, Silvy
    University Hospital Leuven, Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
    Meersmans, Karen
    University Hospital Leuven, Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
    Blin, Olivier
    Service de Pharmacologie Clinique et Pharmacovigilance, Institut de Neurosciences des Systèmes, Aix Marseille University, APHM, INSERM, Marseille, France.
    Richardson, Jill
    Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevenage, UK.
    De Roeck, Ellen
    Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
    Sleegers, Kristel
    Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Neurodegenerative Brain Diseases Group, Center for Molecular Neurology, VIB, Flanders, Belgium.
    Bordet, Régis
    University of Lille, INSERM, CHU, Degenerative and Vascular Cognitive Disorders, Lille, Lille, France.
    Rami, Lorena
    Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clinic-IDIBAPS, Barcelona, Spain.
    Kettunen, Petronella
    Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Memory Clinic at Department of Neuropsychiatry, Sahlgrenska University Hospital, Gothenburg, Sweden; Nuffield Department of Clinical Neurosciences, University of Oxford, West Wing, John Radcliffe Hospital, Oxford, UK.
    Tsolaki, Magda
    First Department of Neurology, AHEPA University Hospital, Makedonia, Thessaloniki, Greece.
    Verhey, Frans
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, The Netherlands.
    Sala, Isabel
    Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
    Lléo, Alberto
    Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
    Peyratout, Gwendoline
    University Hospital of Lausanne, Lausanne, Switzerland.
    Tainta, Mikel
    CITA-Alzheimer Foundation, San Sebastian, Spain.
    Johannsen, Peter
    Danish Dementia Research Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
    Freund-Levi, Yvonne
    Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Frölich, Lutz
    Department of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany.
    Dobricic, Valerija
    Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Germany.
    Engelborghs, Sebastiaan
    Institute Born-Bunge, University of Antwerp, Antwerp, Belgium; Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Germany; Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.
    Frisoni, Giovanni B
    University of Geneva, Geneva, Switzerland.
    Molinuevo, José L
    Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clinic-IDIBAPS, Barcelona, Spain; Barcelona Beta Brain Research Center, Pasqual Maragall Foundation, Barcelona, Spain.
    Wallin, Anders
    Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Popp, Julius
    University Hospital of Lausanne, Lausanne, Switzerland; Geriatric Psychiatry, Department of Mental Health and Psychiatry, Geneva University Hospitals, Geneva, Switzerland.
    Martinez-Lage, Pablo
    CITA-Alzheimer Foundation, San Sebastian, Spain.
    Bertram, Lars
    University of Lübeck, Lübeck, Germany.
    Barkhof, Frederik
    Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam University Medical Centers, Amsterdam Neuroscience, Amsterdam, The Netherlands.
    Ashton, Nicholas
    Steno Diabetes Center Copenhagen, Gentofte, Denmark; Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Blennow, Kaj
    Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
    Zetterberg, Henrik
    Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; UK Dementia Research Institute at UCL, London, UK.
    Streffer, Johannes
    Experimental Medicine, Janssen Pharmaceutical Companies, Beerse, Belgium.
    Visser, Pieter J
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, The Netherlands; Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Amsterdam University Medical Centers, Amsterdam Neuroscience, Amsterdam, The Netherlands.
    Lovestone, Simon
    Department of Psychiatry, University of Oxford, Oxford, UK.
    Legido-Quigley, Cristina
    Institute of Pharmaceutical Science, King's College London, London, UK; Steno Diabetes Center Copenhagen, Gentofte, Denmark.
    Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort2019In: Alzheimer's & Dementia: Journal of the Alzheimer's Association, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 15, no 6, p. 817-827Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: A critical and as-yet unmet need in Alzheimer's disease (AD) is the discovery of peripheral small molecule biomarkers. Given that brain pathology precedes clinical symptom onset, we set out to test whether metabolites in blood associated with pathology as indexed by cerebrospinal fluid (CSF) AD biomarkers.

    METHODS: This study analyzed 593 plasma samples selected from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery study, of individuals who were cognitively healthy (n = 242), had mild cognitive impairment (n = 236), or had AD-type dementia (n = 115). Logistic regressions were carried out between plasma metabolites (n = 883) and CSF markers, magnetic resonance imaging, cognition, and clinical diagnosis.

    RESULTS: Eight metabolites were associated with amyloid β and one with t-tau in CSF, these were primary fatty acid amides (PFAMs), lipokines, and amino acids. From these, PFAMs, glutamate, and aspartate also associated with hippocampal volume and memory.

    DISCUSSION: PFAMs have been found increased and associated with amyloid β burden in CSF and clinical measures.

  • 44.
    Küçükali, Fahri
    et al.
    Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
    Neumann, Alexander
    Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
    Van Dongen, Jasper
    Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
    De Pooter, Tim
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Neuromics Support Facility, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
    Joris, Geert
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Neuromics Support Facility, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
    De Rijk, Peter
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Neuromics Support Facility, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
    Ohlei, Olena
    Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, Lübeck, Germany.
    Dobricic, Valerija
    Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, Lübeck, Germany.
    Bos, Isabelle
    Netherlands Institute for Health Services Research, Utrecht, Netherlands.
    Vos, Stephanie J. B.
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, Netherlands.
    Engelborghs, Sebastiaan
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Department of Neurology and Brussels Integrated Center for Brain and Memory (Bru-BRAIN), Universitair Ziekenhuis Brussel (UZ Brussel) and Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium.
    De Roeck, Ellen
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.
    Vandenberghe, Rik
    University Hospital Leuven, Leuven, Belgium; Department of Neurosciences, Laboratory for Cognitive Neurology, KU Leuven, Leuven, Belgium.
    Gabel, Silvy
    University Hospital Leuven, Leuven, Belgium; Department of Neurosciences, Laboratory for Cognitive Neurology, KU Leuven, Leuven, Belgium.
    Meersmans, Karen
    University Hospital Leuven, Leuven, Belgium; Department of Neurosciences, Laboratory for Cognitive Neurology, KU Leuven, Leuven, Belgium.
    Tsolaki, Magda
    1st Department of Neurology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Makedonia, Thessaloniki, Greece.
    Verhey, Frans
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, Netherlands; Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands.
    Martinez-Lage, Pablo
    Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, San Sebastian, Spain.
    Tainta, Mikel
    Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, San Sebastian, Spain.
    Frisoni, Giovanni
    Department of Psychiatry, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland; RCCS Instituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
    Blin, Oliver
    Clinical Pharmacology & Pharmacovigilance Department, Marseille University Hospital, Marseille, France.
    Richardson, Jill C.
    Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevanage, United Kingdom.
    Bordet, Régis
    Neuroscience & Cognition, CHU de Lille, University of Lille, Inserm, France.
    Scheltens, Philip
    Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, Netherlands; Alzheimer's Disease Neuroimaging Initiative (ADNI).
    Popp, Julius
    Department of Geriatric Psychiatry, University Hospital of Psychiatry Zürich, Zürich, Switzerland; Department of Psychiatry, Old Age Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
    Peyratout, Gwendoline
    Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
    Johannsen, Peter
    Clinical Drug Development, Novo Nordisk, Copenhagen, Denmark.
    Frölich, Lutz
    Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
    Freund-Levi, Yvonne
    Örebro University, School of Medical Sciences. Departments of Geriatrics, University Hospital Örebro, Örebro, Sweden; Department of Clinical Science and Education, Södertälje Hospital, Södersjukhuset Karolinska Institutet, Stockholm, Sweden.
    Streffer, Johannes
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
    Lovestone, Simon
    Department of Psychiatry, University of Oxford, Oxford, United Kingdom; Janssen Medical Ltd, High Wycombe, United Kingdom.
    Legido-Quigley, Cristina
    Steno Diabetes Center, Copenhagen, Denmark; Institute of Pharmaceutical Sciences, King's College London, London, United Kingdom.
    Kate, Mara Ten
    Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, Netherlands; Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands.
    Barkhof, Frederik
    Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, Netherlands; Queen Square Institute of Neurology and Centre for Medical Image Computing, University College London, London, United Kingdom.
    Zetterberg, Henrik
    Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; UK Dementia Research Institute, University College London, London, United Kingdom; Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
    Bertram, Lars
    Lübeck Interdisciplinary Platform for Genome Analytics (LIGA), University of Lübeck, Lübeck, Germany; Centre for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, Norway.
    Strazisar, Mojca
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Neuromics Support Facility, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
    Visser, Pieter Jelle
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, Netherlands; Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, Netherlands.
    Van Broeckhoven, Christine
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Neurodegenerative Brain Diseases Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
    Sleegers, Kristel
    Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
    Whole-exome rare-variant analysis of Alzheimer's disease and related biomarker traits2023In: Alzheimer's & Dementia: Journal of the Alzheimer's Association, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 19, no 6, p. 2317-2331Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Despite increasing evidence of a role of rare genetic variation in the risk of Alzheimer's disease (AD), limited attention has been paid to its contribution to AD-related biomarker traits indicative of AD-relevant pathophysiological processes.

    METHODS: We performed whole-exome gene-based rare-variant association studies (RVASs) of 17 AD-related traits on whole-exome sequencing (WES) data generated in the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study (n = 450) and whole-genome sequencing (WGS) data from ADNI (n = 808).

    RESULTS: Mutation screening revealed a novel probably pathogenic mutation (PSEN1 p.Leu232Phe). Gene-based RVAS revealed the exome-wide significant contribution of rare coding variation in RBKS and OR7A10 to cognitive performance and protection against left hippocampal atrophy, respectively.

    DISCUSSION: The identification of these novel gene-trait associations offers new perspectives into the role of rare coding variation in the distinct pathophysiological processes culminating in AD, which may lead to identification of novel therapeutic and diagnostic targets.

  • 45.
    Lleó, Alberto
    et al.
    Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; Centre of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
    Alcolea, Daniel
    Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; Centre of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
    Martínez-Lage, Pablo
    Center for Research and Advanced Therapies, Fundación CITA-alzheimer Fundazioa, San Sebastian, Spain.
    Scheltens, Philip
    Amsterdam UMC, Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
    Parnetti, Lucilla
    Centre for Memory Disturbances, Section of Neurology, Lab of Clinical Neurochemistry, University of Perugia, Perugia, Italy.
    Poirier, Judes
    Centre for the Studies on the Prevention of Alzheimer's Disease, Douglas Mental Health University Institute, Montréal, QC, Canada.
    Simonsen, Anja H.
    Danish Dementia Research Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
    Verbeek, Marcel M.
    Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Center, Nijmegen, the Netherlands; Department of Laboratory Medicine, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Radboud Alzheimer Center, Nijmegen, the Netherlands.
    Rosa-Neto, Pedro
    Centre for the Studies on the Prevention of Alzheimer's Disease, Douglas Mental Health University Institute, Montréal, QC, Canada.
    Slot, Rosalinde E.R.
    Amsterdam UMC, Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
    Tainta, Mikel
    Center for Research and Advanced Therapies, Fundación CITA-alzheimer Fundazioa, San Sebastian, Spain.
    Izaguirre, Andrea
    Center for Research and Advanced Therapies, Fundación CITA-alzheimer Fundazioa, San Sebastian, Spain.
    Reijs, Babette L.R.
    Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
    Farotti, Lucia
    Centre for Memory Disturbances, Section of Neurology, Lab of Clinical Neurochemistry, University of Perugia, Perugia, Italy.
    Tsolaki, Magda
    1st Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, Makedonia, Greece; Alzheimer Hellas, Thessaloniki, Greece.
    Vandenbergue, Rik
    University Hospital Leuven, Leuven, Belgium; Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
    Freund-Levi, Yvonne
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet Center for Alzheimer Research, Division of Clinical Geriatrics, Huddinge; Department of Old Age Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
    Verhey, Frans R.J.
    Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
    Clarimón, Jordi
    Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; Centre of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
    Fortea, Juan
    Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; Centre of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
    Frolich, Lutz
    Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
    Santana, Isabel
    Dementia Clinic, Centro Hospitalar e Universitário de Coimbra and Faculty of Medicine, Universidade de Coimbra, Coimbra, Portugal.
    Molinuevo, José Luis
    ICN Hospital Clinic i Universitari, Barcelona, Spain.
    Lehmann, Sylvain
    Univ Montpellier, CHU Montpellier, Montpellier, France.
    Visser, Pieter J.
    Amsterdam UMC, Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, the Netherlands.
    Teunissen, Charlotte E.
    Amsterdam UMC, Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
    Zetterberg, Henrik
    Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, University College London, Queen Square, London, United Kingdom; UK Dementia Research Institute at UCL, London, United Kingdom.
    Blennow, Kaj
    Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
    Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer's disease continuum in the BIOMARKAPD study2019In: Alzheimer's & Dementia: Journal of the Alzheimer's Association, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 15, no 6, p. 742-753Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Within-person trajectories of cerebrospinal fluid (CSF) biomarkers in Alzheimer's disease (AD) are not well defined.

    METHODS: We included 467 subjects from the BIOMARKAPD study with at least two serial CSF samples. Diagnoses were subjective cognitive decline (n = 75), mild cognitive impairment (n = 128), and AD dementia (n = 110), and a group of cognitively unimpaired subjects (n = 154) were also included. We measured baseline and follow-up CSF levels of total tau (t-tau), phosphorylated tau (p-tau), YKL-40, and neurofilament light (NfL). Median CSF sampling interval was 2.1 years.

    RESULTS: CSF levels of t-tau, p-tau, NfL, and YKL-40 were 2% higher per each year of baseline age in controls (P <.001). In AD, t-tau levels were 1% lower (P <.001) and p-tau levels did not change per each year of baseline age. Longitudinally, only NfL (P <.001) and YKL-40 (P <.02) increased during the study period.

    DISCUSSION: All four CSF biomarkers increase with age, but this effect deviates in AD for t-tau and p-tau.

  • 46.
    Mattsson, Niklas
    et al.
    Clinical Memory Research Unit, Clinical Sciences Malmö, Lund University, Lund, Sweden.
    Freund-Levi, Yvonne
    Department of Geriatrics, Karolinska University Hospital Huddinge, Section of Clinical Geriatrics, Institution of NVS, Karolinska Institutet, Stockholm, Sweden.
    Ossenkoppele, Rik
    Clinical Memory Research Unit, Clinical Sciences Malmö, Lund University, Lund, Sweden; Department of Neurology and Alzheimer Center, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands; Department of Radiology and Nuclear Medicine, VU University Medical Center, Neuroscience Campus Amsterdam, Amsterdam, the Netherlands.
    Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease2018In: Alzheimer's & Dementia: Journal of the Alzheimer's Association, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 14, no 7, p. 913-924Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology.

    METHODS: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location.

    RESULTS: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aβ+ cognitively normal and Aβ+ mild cognitive impairment (P < .05) but not in Aβ+ AD dementia (P = .66). The prevalence was highest in Northern Europe but did not vary by sex or education.

    DISCUSSION: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aβ pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.

  • 47.
    Neumann, Alexander
    et al.
    Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
    Küçükali, Fahri
    Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
    Bos, Isabelle
    Netherlands Institute for Health Services Research, Utrecht, the Netherlands.
    Vos, Stephanie J. B.
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
    Engelborghs, Sebastiaan
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Universitair Ziekenhuis Brussel (UZ Brussel) and Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium .
    De Pooter, Tim
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Neuromics Support Facility, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium .
    Joris, Geert
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Neuromics Support Facility, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium .
    De Rijk, Peter
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.
    De Roeck, Ellen
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.
    Tsolaki, Magda
    1st Department of Neurology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Makedonia, Thessaloniki, Greece.
    Verhey, Frans
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands; Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, San Sebastian, Spain.
    Martinez-Lage, Pablo
    Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, San Sebastian, Spain.
    Tainta, Mikel
    Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, San Sebastian, Spain.
    Frisoni, Giovanni
    Department of Psychiatry, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland; RCCS Instituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
    Blin, Oliver
    Clinical Pharmacology & Pharmacovigilance Department, Marseille University Hospital, Marseille, France.
    Richardson, Jill
    Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevanage, UK.
    Bordet, Régis
    Neuroscience & Cognition, CHU de Lille, University of Lille, Inserm, France.
    Scheltens, Philip
    Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, the Netherlands.
    Popp, Julius
    Department of Geriatric Psychiatry, University Hospital of Psychiatry Zürich, Zürich, Switzerland; Old Age Psychiatry, Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
    Peyratout, Gwendoline
    Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
    Johannsen, Peter
    Clinical Drug Development, Novo Nordisk, Copenhagen, Denmark.
    Frölich, Lutz
    Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
    Vandenberghe, Rik
    Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
    Freund-Levi, Yvonne
    Örebro University, School of Medical Sciences. Center for Alzheimer Research, Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society Karolinska Institute Stockholm Sweden, Stockholm, Sweden.
    Streffer, Johannes
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
    Lovestone, Simon
    Department of Psychiatry, University of Oxford, Oxford, UK; Janssen Medical Ltd, High Wycombe, UK.
    Legido-Quigley, Cristina
    Steno Diabetes Center, Copenhagen, Denmark; Institute of Pharmaceutical Sciences, King's College London, London, UK.
    Ten Kate, Mara
    Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, the Netherlands; Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
    Barkhof, Frederik
    Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands; Institutes of Neurology and Healthcare Engineering, University College London, London, UK.
    Strazisar, Mojca
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Neuromics Support Facility, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
    Zetterberg, Henrik
    Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; UK Dementia Research Institute, University College London, London, UK; Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
    Bertram, Lars
    Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany; Centre for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, Norway.
    Visser, Pieter Jelle
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands; Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, the Netherlands .
    van Broeckhoven, Christine
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Neurodegenerative Brain Diseases Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
    Sleegers, Kristel
    Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
    Rare variants in IFFO1, DTNB, NLRC3 and SLC22A10 associate with Alzheimer's disease CSF profile of neuronal injury and inflammation2022In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 27, no 4, p. 1990-1999Article in journal (Refereed)
    Abstract [en]

    Alzheimer's disease (AD) biomarkers represent several neurodegenerative processes, such as synaptic dysfunction, neuronal inflammation and injury, as well as amyloid pathology. We performed an exome-wide rare variant analysis of six AD biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and Neurogranin) to discover genes associated with these markers. Genetic and biomarker information was available for 480 participants from two studies: EMIF-AD and ADNI. We applied a principal component (PC) analysis to derive biomarkers combinations, which represent statistically independent biological processes. We then tested whether rare variants in 9576 protein-coding genes associate with these PCs using a Meta-SKAT test. We also tested whether the PCs are intermediary to gene effects on AD symptoms with a SMUT test. One PC loaded on NfL and YKL-40, indicators of neuronal injury and inflammation. Four genes were associated with this PC: IFFO1, DTNB, NLRC3, and SLC22A10. Mediation tests suggest, that these genes also affect dementia symptoms via inflammation/injury. We also observed an association between a PC loading on Neurogranin, a marker for synaptic functioning, with GABBR2 and CASZ1, but no mediation effects. The results suggest that rare variants in IFFO1, DTNB, NLRC3, and SLC22A10 heighten susceptibility to neuronal injury and inflammation, potentially by altering cytoskeleton structure and immune activity disinhibition, resulting in an elevated dementia risk. GABBR2 and CASZ1 were associated with synaptic functioning, but mediation analyses suggest that the effect of these two genes on synaptic functioning is not consequential for AD development.

  • 48.
    Nordberg, Agneta
    et al.
    Geriatriska kliniken, Karolinska universitetssjukhuset, Huddinge, Sweden.
    Eriksdotter-Jönhagen, Maria
    Geriatriska kliniken, Karolinska universitetssjukhuset, Huddinge, Sweden.
    Garlind, Anita
    Södra Stockholms geriatriska klinik, Dalens sjukhus, Stockholm, Sweden.
    Grut, Michaela
    Danderydsgeriatriken, Danderyds sjukhus, Stockholm, Sweden.
    Freund-Levi, Yvonne
    Geriatriska kliniken, Karolinska universitetssjukhuset, Huddinge, Sweden.
    Cornelius, Christel
    Geriatriska kliniken, Karolinska universitetssjukhuset, Huddinge, Sweden.
    Ekström, Anna
    Södersjukhuset, Stockholm, Sweden.
    Fastbom, Johan
    Aging Research Center, Äldrecentrum, Stockholm, Sweden.
    Sedvall, Marie
    Husläkarmottagningen Bennedich & Björk, Stockholm, Sweden.
    Viitanen, Matti
    Geriatriska kliniken, Karolinska universitetssjukhuset, Huddinge, Sweden.
    Värt ge symtomlindrande läkemedel vid Alzheimers sjukdom [Administration of symptom-relieving drugs in Alzheimer disease is beneficial]2006In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 103, no 6, p. 369-371Article in journal (Refereed)
  • 49.
    Nyberg, Svante
    et al.
    AstraZeneca R&D, Neuroscience Therapy Area, Södertälje, Sweden.
    Eriksdotter Jönhagen, Maria
    NVS Department, Karolinska Institute, Karolinska University Hospital Huddinge, Huddinge, Sweden.
    Cselényi, Zsolt
    AstraZeneca R&D, Neuroscience Therapy Area, Södertälje, Sweden.
    Halldin, Christer
    PET Centre, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Julin, Per
    AstraZeneca R&D, Neuroscience Therapy Area, Södertälje, Sweden.
    Olsson, Hans
    AstraZeneca R&D, Neuroscience Therapy Area, Södertälje, Sweden.
    Freund-Levi, Yvonne
    NVS Department, Karolinska Institute, Karolinska University Hospital Huddinge, Huddinge, Sweden.
    Andersson, Jan
    PET Centre, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Varnäs, Katarina
    PET Centre, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Svensson, Samuel
    AstraZeneca R&D, Neuroscience Therapy Area, Södertälje, Sweden.
    Farde, Lars
    AstraZeneca R&D, Neuroscience Therapy Area, Södertälje, Sweden; PET Centre, Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Detection of amyloid in Alzheimer's disease with positron emission tomography using [11C]AZD21842009In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 36, no 11, p. 1859-1863Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Current positron emission tomography (PET) radioligands for detection of Aβ amyloid in Alzheimer's disease (AD) are not ideal for quantification. To improve the signal to noise ratio we have developed the radioligand [11C]AZD2184 and report here the first clinical evaluation.

    METHODS: Eight AD patients and four younger control subjects underwent 93-min PET measurements with [11C]AZD2184. A ratio approach using the cerebellum as reference region was applied to determine binding parameters.

    RESULTS: Brain uptake of [11C]AZD2184 peaked within 1 min at 3-4% of injected radioactivity. AD patients had high radioactivity in cortical regions while controls had uniformly low radioactivity uptake. Specific binding peaked within 30 min at which time standardized uptake value ratios (SUVR) ranged between 1.19 and 2.57.

    CONCLUSION: [11C]AZD2184 is a promising radioligand for detailed mapping of Aβ amyloid depositions in Alzheimer's disease, due to low non-specific binding, high signal to background ratio and reversible binding as evident from early peak equilibrium.

  • 50.
    Palmblad, Jan
    et al.
    Department of Medicine, Division of Hematology, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Eriksdotter-Jönhagen, Maria
    Department of NVS, Section of Clinical Geriatrics, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Freund-Levi, Yvonne
    Department of NVS, Section of Clinical Geriatrics, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Cederholm, Tommy
    Clinical Nutrition Research, Department of Public Health and Caring Sciences, Uppsala University Hospital, Uppsala, Sweden.
    [Omega-3-fatty acids protect against dementia. Also early symptoms of mild Alzheimer disease seem to be inhibited]2007In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 104, no 44, p. 3268-3271Article in journal (Refereed)
12 1 - 50 of 73
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf