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van Maurik, I. S., Vos, S. J., Bos, I., Bouwman, F. H., Teunissen, C. E., Scheltens, P., . . . van der Flier, W. M. (2019). Biomarker-based prognosis for people with mild cognitive impairment (ABIDE): a modelling study. Lancet Neurology
Open this publication in new window or tab >>Biomarker-based prognosis for people with mild cognitive impairment (ABIDE): a modelling study
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2019 (English)In: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND: Biomarker-based risk predictions of dementia in people with mild cognitive impairment are highly relevant for care planning and to select patients for treatment when disease-modifying drugs become available. We aimed to establish robust prediction models of disease progression in people at risk of dementia.

METHODS: In this modelling study, we included people with mild cognitive impairment (MCI) from single-centre and multicentre cohorts in Europe and North America: the European Medical Information Framework for Alzheimer's Disease (EMIF-AD; n=883), Alzheimer's Disease Neuroimaging Initiative (ADNI; n=829), Amsterdam Dementia Cohort (ADC; n=666), and the Swedish BioFINDER study (n=233). Inclusion criteria were a baseline diagnosis of MCI, at least 6 months of follow-up, and availability of a baseline Mini-Mental State Examination (MMSE) and MRI or CSF biomarker assessment. The primary endpoint was clinical progression to any type of dementia. We evaluated performance of previously developed risk prediction models-a demographics model, a hippocampal volume model, and a CSF biomarkers model-by evaluating them across cohorts, incorporating different biomarker measurement methods, and determining prognostic performance with Harrell's C statistic. We then updated the models by re-estimating parameters with and without centre-specific effects and evaluated model calibration by comparing observed and expected survival. Finally, we constructed a model combining markers for amyloid deposition, tauopathy, and neurodegeneration (ATN), in accordance with the National Institute on Aging and Alzheimer's Association research framework.

FINDINGS: We included all 2611 individuals with MCI in the four cohorts, 1007 (39%) of whom progressed to dementia. The validated demographics model (Harrell's C 0·62, 95% CI 0·59-0·65), validated hippocampal volume model (0·67, 0·62-0·72), and updated CSF biomarkers model (0·72, 0·68-0·74) had adequate prognostic performance across cohorts and were well calibrated. The newly constructed ATN model had the highest performance (0·74, 0·71-0·76).

INTERPRETATION: We generated risk models that are robust across cohorts, which adds to their potential clinical applicability. The models could aid clinicians in the interpretation of CSF biomarker and hippocampal volume results in individuals with MCI, and help research and clinical settings to prepare for a future of precision medicine in Alzheimer's disease. Future research should focus on the clinical utility of the models, particularly if their use affects participants' understanding, emotional wellbeing, and behaviour.

FUNDING: ZonMW-Memorabel.

Place, publisher, year, edition, pages
The Lancet Publishing Group, 2019
National Category
Medical and Health Sciences Geriatrics Neurology
Identifiers
urn:nbn:se:oru:diva-77105 (URN)10.1016/S1474-4422(19)30283-2 (DOI)31526625 (PubMedID)
Available from: 2019-10-09 Created: 2019-10-09 Last updated: 2019-10-09Bibliographically approved
Bos, I., Vos, S., Verhey, F., Scheltens, P., Teunissen, C., Engelborghs, S., . . . Visser, P. J. (2019). Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum. Alzheimer's & Dementia, 15(5), 644-654
Open this publication in new window or tab >>Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum
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2019 (English)In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 15, no 5, p. 644-654Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
APOE, Alzheimer's disease, Amyloid-β, Cerebrospinal fluid, Cognition, Neurofilament light, Neurogranin, YKL-40
National Category
Medical and Health Sciences Neurology
Identifiers
urn:nbn:se:oru:diva-74036 (URN)10.1016/j.jalz.2019.01.004 (DOI)000467220800005 ()30853464 (PubMedID)
Available from: 2019-05-06 Created: 2019-05-06 Last updated: 2019-06-19Bibliographically approved
Vermunt, L., Sikkes, S. A. M., van den Hout, A., Handels, R., Bos, I., van der Flier, W. M., . . . Visser, P. J. (2019). Duration of preclinical, prodromal, and dementia stages of Alzheimer's disease in relation to age, sex, and APOE genotype. Alzheimer's & Dementia, 15(7), 888-898
Open this publication in new window or tab >>Duration of preclinical, prodromal, and dementia stages of Alzheimer's disease in relation to age, sex, and APOE genotype
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2019 (English)In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 15, no 7, p. 888-898Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: We estimated the age-specific duration of the preclinical, prodromal, and dementia stages of Alzheimer's disease (AD) and the influence of sex, setting, apolipoprotein E (APOE) genotype, and cerebrospinal fluid tau on disease duration.

METHODS: We performed multistate modeling in a combined sample of 6 cohorts (n = 3268) with death as the end stage and estimated the preclinical, prodromal, and dementia stage duration.

RESULTS: The overall AD duration varied between 24 years (age 60) and 15 years (age 80). For individuals presenting with preclinical AD, age 70, the estimated preclinical AD duration was 10 years, prodromal AD 4 years, and dementia 6 years. Male sex, clinical setting, APOE ε4 allele carriership, and abnormal cerebrospinal fluid tau were associated with a shorter duration, and these effects depended on disease stage.

DISCUSSION: Estimates of AD disease duration become more accurate if age, sex, setting, APOE, and cerebrospinal fluid tau are taken into account. This will be relevant for clinical practice and trial design.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
APOE, Alzheimer's disease, Clinical setting, Dementia, Disease duration, Multistate model, Preclinical, Prodromal, Progression
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-75631 (URN)10.1016/j.jalz.2019.04.001 (DOI)000475846300004 ()31164314 (PubMedID)2-s2.0-85066298869 (Scopus ID)
Note

Funding Agency:

NIA NIH HHS

Available from: 2019-08-20 Created: 2019-08-20 Last updated: 2019-08-20Bibliographically approved
Jernerén, F., Cederholm, T., Refsum, H., Smith, A. D., Turner, C., Palmblad, J., . . . Freund-Levi, Y. (2019). 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 Study. Journal of Alzheimer's Disease, 69(1), 189-197
Open this publication in new window or tab >>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 Study
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2019 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 69, no 1, p. 189-197Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
IOS Press, 2019
Keywords
Alzheimer's disease, B vitamins, cognition, dementia, homocysteine, omega-3 fatty acids
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-74426 (URN)10.3233/JAD-181148 (DOI)000467519100017 ()30958356 (PubMedID)2-s2.0-85065659695 (Scopus ID)
Funder
Stockholm County CouncilThe Karolinska Institutet's Research FoundationThe Dementia Association - The National Association for the Rights of the DementedStiftelsen Gamla TjänarinnorThe Swedish Brain FoundationSwedish Nutrition Foundation (SNF)Gun och Bertil Stohnes StiftelseÅke Wiberg Foundation
Note

Funding Agencies:

Funds of Capio

Swedish Alzheimer Foundation  

Norwegian Research Council  

Odd Fellows 

Swedish Society of Physicians  

Lion's Sweden 

Available from: 2019-05-28 Created: 2019-05-28 Last updated: 2019-05-28Bibliographically approved
Bos, I., Vos, S. J. B., Jansen, W. J., Vandenberghe, R., Gabel, S., Estanga, A., . . . Visser, P. J. (2018). Amyloid-β, Tau, and Cognition in Cognitively Normal Older Individuals: Examining the Necessity to Adjust for Biomarker Status in Normative Data.. Frontiers in Aging Neuroscience, 10, Article ID 193.
Open this publication in new window or tab >>Amyloid-β, Tau, and Cognition in Cognitively Normal Older Individuals: Examining the Necessity to Adjust for Biomarker Status in Normative Data.
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2018 (English)In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 10, article id 193Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018
Keywords
Alzheimer's disease, amyloid-beta, cognition, neuropsychological examination, normative data, tau
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-74037 (URN)10.3389/fnagi.2018.00193 (DOI)000436126300002 ()29988624 (PubMedID)
Available from: 2019-05-06 Created: 2019-05-06 Last updated: 2019-06-18Bibliographically approved
Faxen-Irving, G., Falahati, F., Basun, H., Eriksdotter, M., Vedin, I., Wahlund, L.-O., . . . Freund-Levi, Y. (2018). Does Fatty Acid Composition in Subcutaneous Adipose Tissue Differ between Patients with Alzheimer's Disease and Cohabiting Proxies?. Journal of Alzheimer's Disease, 61(2), 515-519
Open this publication in new window or tab >>Does Fatty Acid Composition in Subcutaneous Adipose Tissue Differ between Patients with Alzheimer's Disease and Cohabiting Proxies?
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2018 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 61, no 2, p. 515-519Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
IOS Press, 2018
Keywords
Alzheimer’s disease, DHA, EPA, cognition, cohabitants, subcutaneous adipose tissue, ω3 fatty acids
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-74038 (URN)10.3233/JAD-170359 (DOI)000422844100004 ()29154271 (PubMedID)2-s2.0-85038834560 (Scopus ID)
Note

Funding agencies:

Stockholm County Council

Karolinska Institutet

Medical Research Council

Funds of Capio

Demensförbundet

Gamla Tjänarinnor

Swedish Alzheimer Foundation

Odd Fellow

Swedish Nutrition Foundation

Gun och Bertil Stohnes Stiftelse

Swedish Society of Physicians

Lion's Sweden

Available from: 2019-05-06 Created: 2019-05-06 Last updated: 2019-06-18Bibliographically approved
Mattsson, N., Freund-Levi, Y. & Ossenkoppele, R. (2018). Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease. Alzheimer's & Dementia, 14(7), 913-924
Open this publication in new window or tab >>Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease
2018 (English)In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 14, no 7, p. 913-924Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
APOE, Age, Alzheimer's disease, Amyloid, CSF, Education, Geographical location, Mild cognitive impairment, PET, Prevalence, Sex, Subjective cognitive decline
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-74057 (URN)10.1016/j.jalz.2018.02.009 (DOI)000438783200009 ()29601787 (PubMedID)2-s2.0-85045929153 (Scopus ID)
Available from: 2019-05-07 Created: 2019-05-07 Last updated: 2019-06-18Bibliographically approved
Bos, I., Verhey, F. R., Ramakers, I. H. G., Jacobs, H. I. L., Soininen, H., Freund-Levi, Y., . . . Vos, S. J. B. (2017). Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline. Alzheimer's Research & Therapy, 9(1), Article ID 101.
Open this publication in new window or tab >>Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline
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2017 (English)In: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 9, no 1, article id 101Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
BioMed Central, 2017
Keywords
Alzheimer’s disease, Amyloid, Cerebrospinal fluid, Cerebrovascular disease, Cognition, MRI, Medial temporal lobe atrophy, Neurodegeneration, Tau
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-74040 (URN)10.1186/s13195-017-0328-9 (DOI)000419007500001 ()29284531 (PubMedID)2-s2.0-85039756986 (Scopus ID)
Funder
EU, FP7, Seventh Framework Programme
Note

Funding agencies:

European Medical Information Framework Alzheimer’s disease (EMIF-AD) project - Innovative Medicines Initiative under EMIF

European Federation of Pharmaceutical Industries and Associations (EFPIA)

Center for Translational Molecular Medicine

European Commission, 5th framework program

Available from: 2019-05-06 Created: 2019-05-06 Last updated: 2019-06-18Bibliographically approved
Karimi, M., Vedin, I., Freund-Levi, Y., Basun, H., Faxén Irving, G., Eriksdotter, M., . . . Palmblad, J. (2017). DHA-rich n-3 fatty acid supplementation decreases DNA methylation in blood leukocytes: the OmegAD study. American Journal of Clinical Nutrition, 106(4), 1157-1165
Open this publication in new window or tab >>DHA-rich n-3 fatty acid supplementation decreases DNA methylation in blood leukocytes: the OmegAD study
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2017 (English)In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 106, no 4, p. 1157-1165Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
HighWire Press, 2017
Keywords
Alzheimer disease, DHA, DNA methylation, EPA, LINE-1, fish oil
National Category
Nutrition and Dietetics Hematology Neurology
Identifiers
urn:nbn:se:oru:diva-74058 (URN)10.3945/ajcn.117.155648 (DOI)000412004300022 ()28855224 (PubMedID)2-s2.0-85031697359 (Scopus ID)
Funder
Stockholm County CouncilThe Dementia Association - The National Association for the Rights of the DementedStiftelsen Gamla TjänarinnorGun och Bertil Stohnes Stiftelse
Note

Funding agencies:

Karolinska Institutet

Funds of Capio

Swedish Alzheimer Foundation

Odd Fellows

Swedish Nutrition Foundation

Swedish Society of Physicians

Lion's Sweden

Pronova Biocare A/S

Available from: 2019-05-07 Created: 2019-05-07 Last updated: 2019-06-18Bibliographically approved
Bloniecki, V., Aarsland, D., Blennow, K., Cummings, J., Falahati, F., Winblad, B. & Freund-Levi, Y. (2017). Effects of Risperidone and Galantamine Treatment on Alzheimer's Disease Biomarker Levels in Cerebrospinal Fluid. Journal of Alzheimer's Disease, 57(2), 387-393
Open this publication in new window or tab >>Effects of Risperidone and Galantamine Treatment on Alzheimer's Disease Biomarker Levels in Cerebrospinal Fluid
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2017 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 57, no 2, p. 387-393Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
IOS Press, 2017
Keywords
Biomarkers, dementia, galantamine, neuropsychiatric symptoms, risperidone
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-74044 (URN)10.3233/JAD-160758 (DOI)000398725100005 ()28269767 (PubMedID)2-s2.0-85033600654 (Scopus ID)
Note

Funding agencies:

Janssen Pharmaceuticals, Stockholm, Sweden

Petrus and Augusta-Hedlunds Foundation

Demensförbundet

Loo and Hans Osterman Foundation Karolinska Institute

Demensförbundet Stockholm

Available from: 2019-05-07 Created: 2019-05-07 Last updated: 2019-06-18Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0001-6863-6679

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