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  • 1.
    Böttiger, Anna K.
    et al.
    Örebro University, School of Health and Medical Sciences.
    Hagnelius, Nils-Olof
    Örebro University, School of Health and Medical Sciences.
    Nilsson, Torbjörn K.
    Örebro University, School of Health and Medical Sciences.
    Mutations in exons 2 and 3 of the FOLR1 gene in demented and non-demented elderly subjects2007In: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 20, no 5, p. 653-662Article in journal (Refereed)
    Abstract [en]

    We have previously reported six novel mutations in the 5'-UTR of the gene for folate receptor-alpha (FOLR1). In our search for additional mutations we screened patients, referred for investigation of suspected dementia (DGM subgroup) by SSCP and DNA sequencing from the end of exon 1 to the first bases of intron 3. We found 4 sequence variations, FOLR1 g.1314G>A, g.1816delC, g.1841G>A, and g.1928C>T. Pyrosequencing genotyping assays were developed for all of them, and 389 active seniors (AS subgroup) and the 202 DGM patients were genotyped for these mutations. The frequency q of the mutated allele was, among the AS subjects, 0.068, 0.0026, 0.0026, and 0.024 respectively, and among the DGM subjects, 0.067, 0.0076, 0.0078, and 0.023. The g.1816delC and g.1841G>A mutations thus were more frequent in the DGM than in the AS subgroup, but the difference did not reach statistical significance. The mutated alleles, FOLR1 1816(-) and 1841A, always occurred together in the same subjects, suggestive of a rare double-mutant haplotype. The two common polymorphisms, FOLR1 g. 1314G>A and g.1928C>T seemed not to raise tHcy plasma levels, whereas the double-mutated g.1816(-)-g.1841A haplotype may possibly have a slight tHcy-raising effect. Thus, so far 8 novel rare FOLR1 mutations with a combined prevalence of approximately 1.3% in Whites as well as two common polymorphisms with 5% and 13%, respectively, have been demonstrated. Only a few of the rare mutations may potentially be associated with raised plasma tHcy concentrations. No association with dementia was found.

  • 2.
    Hagnelius, Nils-Olof
    Örebro University, School of Health and Medical Sciences.
    Vascular mechanisms in dementia with special reference to folate and fibrinolysis2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this thesis was to study the biomarker homocysteine and other novel potential vascular risk factors for dementia. In an out-patient based study of a cohort of 926 consecutive subjects referred to our Memory Unit during 1996―2000, serum-folate was lower and total plasma homocysteine (tHcy) and serum methyl malonate were higher in subjects being prescribed with B12. In the subgroup diagnosed with dementia and with a positive family history of dementia, tHcy was higher than in the subgroup diagnosed as non-demented. It is necessary to supplement subjects with vitamin B12 deficiency with B12, but our results indicate that it is not sufficient with B12 alone because this gives rise to intracellular folate deficiency. We also found indications of a genetic component in dementia because tHcy was higher in the group with a positive family history of dementia. These findings prompted further studies of homocysteine metabolism. The frequency of mutations in the gene for folate receptor-α (FOLR-1), and the fibrinolytic pattern in dementia and non-dementia were studied in the two cohorts DGM (n=300) and AS (n=389). The DGM cohort is a consecutive series of subjects attending our Memory Care Unit for investigation of suspected cognitive problems or dementia between 2003 - 2007. The AS (= active seniors) cohort comprises retired, apparently healthy subjects from central Sweden, actively participating in study circles. A rare haplotype in the FOLR-1, with mutations in two nearby loci, was discovered, possibly associated with lower serum-folate and higher tHcy concentrations and was more frequent in the DGM group. The transport of folate to the CSF was studied in the DGM-cohort. Dementia with a vascular component was associated with a lower CSF to serum folate ratio indicative of reduced transport of folate to the CSF and further to the brain. The vascular endothelial derived fibrinolytic markers tPA, tPA/PAI-1-complex, and vWF were not only higher in vascular dementia (VaD) but also in Alzheimer’s Disease (AD) when compared to the AS group. The impaired fibrinolytic activity in both vascular dementia and in AD is a novel finding, signifying a vascular component in the development of dementia. In conclusion we found that both hereditary and nutritional background factors were linked to dementia and furthermore that a dysregulated fibrinolysis was linked to both VaD and AD.

    List of papers
    1. High homocysteine and methylmalonate among demented and non-demented elderly receiving vitamin-B12 prescription and home help service
    Open this publication in new window or tab >>High homocysteine and methylmalonate among demented and non-demented elderly receiving vitamin-B12 prescription and home help service
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background & Aims: Total homocysteine (tHcy) has been suggested as a dementia risk factor. Our aim was to investigate potential differences in tHcy and its determinants (mainly Serum-B12 and Serum-folate) in relation dementia. We examined the effect of vitamin-B12 prescription, whether a family history of dementia, or the need for home help service might have influence on tHcy.

    Methods: A cross sectional monocenter study comprising 926 consecutive subjects attending our Memory Care Unit.

    Results: Demented subjects being prescribed vitamin-B12 had higher Serum-B12 (p =0.025) but also higher tHcy (p =<0.001) and S-methylmalonate (p =0.032), and lower Serum-folate (p<0.001) than those who did not receive B12 prescriptions. tHcy levels were higher in subjects in need of home help service (non-dementia: p= 0.007), this group also had lower S-albumin (dementia: p<0.001; non-dementia: p=0.004). In multivariate logistic regression analysis with diagnosis of dementia as outcome, both vitamin-B12 prescriptions, family history of dementia, and existent home help service, predicted dementia (p=0.037; 0.044; 0.002 respectively).

    Conclusion: Elderly subjects on vitamin-B12 prescription appear to have unmet needs of nutritional support, causing elevated homocysteine levels. The home help service should pay a closer attention to nutritional aspects and drug compliance among geriatric patients.

    Keywords
    homocysteine, dementia, vitamin-B12, folate, home help service
    National Category
    Geriatrics Medical and Health Sciences
    Research subject
    Medicine
    Identifiers
    urn:nbn:se:oru:diva-7842 (URN)
    Available from: 2009-09-09 Created: 2009-09-08 Last updated: 2017-10-18Bibliographically approved
    2. Mutations in exons 2 and 3 of the FOLR1 gene in demented and non-demented elderly subjects
    Open this publication in new window or tab >>Mutations in exons 2 and 3 of the FOLR1 gene in demented and non-demented elderly subjects
    2007 (English)In: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 20, no 5, p. 653-662Article in journal (Refereed) Published
    Abstract [en]

    We have previously reported six novel mutations in the 5'-UTR of the gene for folate receptor-alpha (FOLR1). In our search for additional mutations we screened patients, referred for investigation of suspected dementia (DGM subgroup) by SSCP and DNA sequencing from the end of exon 1 to the first bases of intron 3. We found 4 sequence variations, FOLR1 g.1314G>A, g.1816delC, g.1841G>A, and g.1928C>T. Pyrosequencing genotyping assays were developed for all of them, and 389 active seniors (AS subgroup) and the 202 DGM patients were genotyped for these mutations. The frequency q of the mutated allele was, among the AS subjects, 0.068, 0.0026, 0.0026, and 0.024 respectively, and among the DGM subjects, 0.067, 0.0076, 0.0078, and 0.023. The g.1816delC and g.1841G>A mutations thus were more frequent in the DGM than in the AS subgroup, but the difference did not reach statistical significance. The mutated alleles, FOLR1 1816(-) and 1841A, always occurred together in the same subjects, suggestive of a rare double-mutant haplotype. The two common polymorphisms, FOLR1 g. 1314G>A and g.1928C>T seemed not to raise tHcy plasma levels, whereas the double-mutated g.1816(-)-g.1841A haplotype may possibly have a slight tHcy-raising effect. Thus, so far 8 novel rare FOLR1 mutations with a combined prevalence of approximately 1.3% in Whites as well as two common polymorphisms with 5% and 13%, respectively, have been demonstrated. Only a few of the rare mutations may potentially be associated with raised plasma tHcy concentrations. No association with dementia was found.

    Place, publisher, year, edition, pages
    Athens, Greece: D.A. Spandidos, 2007
    National Category
    Medical and Health Sciences Geriatrics
    Research subject
    Medicine
    Identifiers
    urn:nbn:se:oru:diva-3036 (URN)17912458 (PubMedID)
    Available from: 2008-11-15 Created: 2008-11-15 Last updated: 2017-12-14Bibliographically approved
    3. CSF/serum folate gradient: physiology and determinants with special reference to dementia
    Open this publication in new window or tab >>CSF/serum folate gradient: physiology and determinants with special reference to dementia
    2008 (English)In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 25, no 6, p. 516-523Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Folate depletion has been implicated as a risk factor for neurodegenerative disorders. We hypothesized that transport of folate to the cerebrospinal fluid (CSF) compartment could be involved in the pathophysiology of these disorders.

    METHODS: The CSF/serum folate gradient (R(CSF/S)) was studied in 205 subjects with suspected cognitive disorder. Its relation to clinical and biochemical indices, including the integrity of the blood-CSF barrier, were characterized.

    RESULTS: In subjects who were diagnosed as nondemented (ND) the mean R(CSF/S )+/- SD was 2.46 +/- 0.62 versus 2.09 +/- 0.67 (p = 0.008) in the dementia subgroup with a vascular component (VaD + mixed). The ND subgroup had higher CSF folate (p = 0.001) and lower serum homocysteine values (p = 0.001) than the VaD + mixed subgroup. The folate gradient R(CSF/S) was negatively correlated with serum folate (p < 0.001, R(2) = 0.518) and to the albumin ratio, a blood-CSF barrier biomarker (beta = -0.235). The Alzheimer patients had R(CSF/S) and albumin ratios similar to the ND subjects.

    CONCLUSION: The R(CSF/S) was significantly lower in the VaD + mixed dementia subgroup, suggestive of a defect in the transport of folate over the choroid plexus that seems to be characteristic of, and limited to, the VaD + mixed dementia subgroup.

    Keywords
    Aged, Aged; 80 and over, Alzheimer Disease/blood/cerebrospinal fluid/epidemiology, Blood-Brain Barrier/*physiology, Case-Control Studies, Choroid Plexus/metabolism, Dementia; Vascular/blood/cerebrospinal fluid/epidemiology, Female, Folic Acid/*blood/*cerebrospinal fluid, Homocysteine/blood, Humans, Linear Models, Male, Middle Aged, Multivariate Analysis, Risk Factors, Serum Albumin/metabolism, Vitamin B 12/blood
    National Category
    Medical and Health Sciences Physiology
    Research subject
    Physiology
    Identifiers
    urn:nbn:se:oru:diva-3509 (URN)10.1159/000129696 (DOI)18463447 (PubMedID)
    Available from: 2008-12-08 Created: 2008-12-08 Last updated: 2018-01-13Bibliographically approved
    4. Fibrinolysis and von Willebrand factor in Alzheimer's disease and vascular dementia: a case-referent study
    Open this publication in new window or tab >>Fibrinolysis and von Willebrand factor in Alzheimer's disease and vascular dementia: a case-referent study
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Introduction: The importance of vascular risk factors for Alzheimer’s disease (AD) is not settled. Our aim was to compare patients with AD or vascular dementia (VaD) with non-demented subjects with regard to endothelial derived fibrinolytic and hemostatic factors.

    Materials and methods: In a cross-sectional mono-center case-referent study in Örebro, Sweden, we consecutively included 95 patients with AD and 55 with VaD and 154 non-demented active seniors (AS). Plasma biomarkers including the endothelial derived fibrinolytic factors: mass concentrations of tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), tPA/PAI-1 complex and von Willebrand factor (vWF), as well as clinical data were analyzed.

    Results: None of the endothelial derived fibrinolytic markers or vWF differed between AD vs. VaD. In comparison with the AS group, tPA was higher in AD (p=0.001) and VaD (p=0.023) but its inhibitor, PAI-1 mass concentration did not differ significantly; tPA/PAI-1 complex was higher in both VaD (p=0.038) and AD (p=0.005). vWF concentration was lower in the AS group (p<0.001) than in both dementia groups.

    Conclusion: Thus, endothelial derived fibrinolytic factors, tPA/PAI-1 complex and vWF, discriminated between the reference group of non-demented elderly and the AD and VaD groups, but not between AD and VaD. This suggests similar disturbances for endothelial derived fibrinolytic and hemostatic factors among AD and VaD patients and may reflect shared vascular pathophysiological mechanisms in the dementias.

    Keywords
    vascular dementia, Alzheimer’s disease, fibrinolysis, hemostasis, von Willebrand factor
    National Category
    Geriatrics Medical and Health Sciences
    Research subject
    Medicine
    Identifiers
    urn:nbn:se:oru:diva-7845 (URN)
    Available from: 2009-09-09 Created: 2009-09-08 Last updated: 2017-10-18Bibliographically approved
    Download full text (pdf)
    FULLTEXT02
  • 3.
    Hagnelius, Nils-Olof
    et al.
    Örebro University, School of Health and Medical Sciences.
    Boman, Kurt
    Umeå universitet.
    Nilsson, Torbjörn K.
    Örebro University, School of Health and Medical Sciences.
    Fibrinolysis and von Willebrand factor in Alzheimer's disease and vascular dementia: a case-referent studyManuscript (preprint) (Other academic)
    Abstract [en]

    Introduction: The importance of vascular risk factors for Alzheimer’s disease (AD) is not settled. Our aim was to compare patients with AD or vascular dementia (VaD) with non-demented subjects with regard to endothelial derived fibrinolytic and hemostatic factors.

    Materials and methods: In a cross-sectional mono-center case-referent study in Örebro, Sweden, we consecutively included 95 patients with AD and 55 with VaD and 154 non-demented active seniors (AS). Plasma biomarkers including the endothelial derived fibrinolytic factors: mass concentrations of tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), tPA/PAI-1 complex and von Willebrand factor (vWF), as well as clinical data were analyzed.

    Results: None of the endothelial derived fibrinolytic markers or vWF differed between AD vs. VaD. In comparison with the AS group, tPA was higher in AD (p=0.001) and VaD (p=0.023) but its inhibitor, PAI-1 mass concentration did not differ significantly; tPA/PAI-1 complex was higher in both VaD (p=0.038) and AD (p=0.005). vWF concentration was lower in the AS group (p<0.001) than in both dementia groups.

    Conclusion: Thus, endothelial derived fibrinolytic factors, tPA/PAI-1 complex and vWF, discriminated between the reference group of non-demented elderly and the AD and VaD groups, but not between AD and VaD. This suggests similar disturbances for endothelial derived fibrinolytic and hemostatic factors among AD and VaD patients and may reflect shared vascular pathophysiological mechanisms in the dementias.

    Download full text (pdf)
    FULLTEXT01
  • 4.
    Hagnelius, Nils-Olof
    et al.
    Örebro University, School of Health and Medical Sciences. Dept of Geriatrics, Örebro University Hospital, Örebro, Sweden.
    Boman, Kurt
    Dept Med, Skellefteå Cty Hosp, Skellefteå, Sweden.
    Nilsson, Torbjörn K.
    Örebro University, School of Health and Medical Sciences. Dept of Laboratory Medicine, Div of Clinical Chemistry, Örebro University Hospital, Örebro, Sweden.
    Fibrinolysis and von Willebrand factor in Alzheimer's disease and vascular dementia: a case-referent study2010In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 126, no 1, p. 35-38Article in journal (Refereed)
  • 5. Hagnelius, Nils-Olof
    et al.
    Wahlund, Lars-Olof
    Nilsson, Torbjörn K.
    Örebro University, School of Health and Medical Sciences.
    CSF/serum folate gradient: physiology and determinants with special reference to dementia2008In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 25, no 6, p. 516-523Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Folate depletion has been implicated as a risk factor for neurodegenerative disorders. We hypothesized that transport of folate to the cerebrospinal fluid (CSF) compartment could be involved in the pathophysiology of these disorders.

    METHODS: The CSF/serum folate gradient (R(CSF/S)) was studied in 205 subjects with suspected cognitive disorder. Its relation to clinical and biochemical indices, including the integrity of the blood-CSF barrier, were characterized.

    RESULTS: In subjects who were diagnosed as nondemented (ND) the mean R(CSF/S )+/- SD was 2.46 +/- 0.62 versus 2.09 +/- 0.67 (p = 0.008) in the dementia subgroup with a vascular component (VaD + mixed). The ND subgroup had higher CSF folate (p = 0.001) and lower serum homocysteine values (p = 0.001) than the VaD + mixed subgroup. The folate gradient R(CSF/S) was negatively correlated with serum folate (p < 0.001, R(2) = 0.518) and to the albumin ratio, a blood-CSF barrier biomarker (beta = -0.235). The Alzheimer patients had R(CSF/S) and albumin ratios similar to the ND subjects.

    CONCLUSION: The R(CSF/S) was significantly lower in the VaD + mixed dementia subgroup, suggestive of a defect in the transport of folate over the choroid plexus that seems to be characteristic of, and limited to, the VaD + mixed dementia subgroup.

  • 6.
    Hagnelius, Nils-Olof
    et al.
    Örebro University, School of Health and Medical Sciences.
    Wahlund, Lars-Olof
    Karolinska Institutet, Neurotec.
    Nilsson, Torbjörn K.
    Örebro University, School of Health and Medical Sciences.
    High homocysteine and methylmalonate among demented and non-demented elderly receiving vitamin-B12 prescription and home help serviceManuscript (preprint) (Other academic)
    Abstract [en]

    Background & Aims: Total homocysteine (tHcy) has been suggested as a dementia risk factor. Our aim was to investigate potential differences in tHcy and its determinants (mainly Serum-B12 and Serum-folate) in relation dementia. We examined the effect of vitamin-B12 prescription, whether a family history of dementia, or the need for home help service might have influence on tHcy.

    Methods: A cross sectional monocenter study comprising 926 consecutive subjects attending our Memory Care Unit.

    Results: Demented subjects being prescribed vitamin-B12 had higher Serum-B12 (p =0.025) but also higher tHcy (p =<0.001) and S-methylmalonate (p =0.032), and lower Serum-folate (p<0.001) than those who did not receive B12 prescriptions. tHcy levels were higher in subjects in need of home help service (non-dementia: p= 0.007), this group also had lower S-albumin (dementia: p<0.001; non-dementia: p=0.004). In multivariate logistic regression analysis with diagnosis of dementia as outcome, both vitamin-B12 prescriptions, family history of dementia, and existent home help service, predicted dementia (p=0.037; 0.044; 0.002 respectively).

    Conclusion: Elderly subjects on vitamin-B12 prescription appear to have unmet needs of nutritional support, causing elevated homocysteine levels. The home help service should pay a closer attention to nutritional aspects and drug compliance among geriatric patients.

    Download full text (pdf)
    FULLTEXT01
  • 7.
    Hagnelius, Nils-Olof
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Geriatric Medicine,, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Wahlund, Lars-Olof
    Department of Neurobiology, Care Sciences and Society, Section of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.
    Schneede, Jörn
    Department of Pharmacology and Clinical Neuroscience, Division of Clinical Pharmacology, University Hospital of Northern Sweden, Umeå, Sweden.
    Nilsson, Torbjörn K.
    Department of Laboratory Medicine, Division of Clinical Chemistry, Örebro University Hospital, Örebro, Sweden.
    Blood concentrations of homocysteine and methylmalonic acid among demented and non-demented Swedish elderly with and without home care services and vitamin B(12) prescriptions2012In: Dementia and geriatric cognitive disorders extra, E-ISSN 1664-5464, Vol. 2, no 1, p. 387-399Article in journal (Refereed)
    Abstract [en]

    Background and Aims: Total plasma homocysteine (tHcy) has been suggested as a risk factor of dementia. Our aim was to investigate potential differences in tHcy status in relation to the prescription of vitamin B(12) and dementia diagnosis. We examined whether vitamin B(12) prescriptions, a family history of dementia, or the need for home care service might be associated with tHcy values.

    Methods: A cross-sectional monocenter study comprising 926 consecutive subjects attending our Memory Care Unit was conducted.

    Results: Demented subjects being prescribed vitamin B(12) had higher serum vitamin B(12) (p = 0.025) but also higher tHcy (p < 0.001) and serum methylmalonate (p = 0.032), and lower serum folate (p < 0.001) than those who did not receive vitamin B(12) prescriptions. tHcy levels were significantly higher in non-demented subjects receiving home care service (p = 0.007). This group also had lower serum albumin (dementia: p < 0.001; non-dementia: p = 0.004). There was no difference in renal function (estimated glomerular filtration rate) in demented or non-demented subjects with or without vitamin B(12) prescriptions (dementia with/without vitamin B(12) prescription: p = 0.561; non-dementia with/without vitamin B(12) prescription: p = 0.710).

    Conclusion: Despite vitamin B(12) prescriptions, demented subjects had higher tHcy and methylmalonate values. The elevated metabolite values could not be explained by differences in renal function. Thus, elderly subjects on vitamin B(12) prescription appear to have unmet nutritional needs.

  • 8. Löf-Ohlin, Zarah M.
    et al.
    Hagnelius, Nils-Olof
    Nilsson, Torbjörn K.
    Örebro University, School of Health and Medical Sciences.
    Relative telomere length in patients with late-onset Alzheimer's dementia or vascular dementia2008In: NeuroReport, ISSN 0959-4965, E-ISSN 1473-558X, Vol. 19, no 12, p. 1199-1202Article in journal (Refereed)
    Abstract [en]

    Telomeres generally shorten with age. An accelerated shortening of the telomeres has been linked to several age-related disorders. We hypothesized that the relative length of telomeres could discriminate between patients with late-onset Alzheimer's disease (AD) and vascular dementia (VaD). A quantitative real-time PCR method was used to calculate the relative telomere length in 76 age-matched and sex-matched, newly diagnosed late-onset AD or VaD patients recruited from our Memory Unit. No significant difference was found in the relative telomere length between AD and VaD cases neither in men (P=0.315) nor women (P=0.12). Thus, we could not confirm that the length of telomeres would predict which form of dementia, late-onset AD or VaD that develops.

  • 9.
    Nilsson, Torbjörn, K.
    et al.
    Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Hagnelius, Nils-Olof
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Folate in dementia and cognitive dysfunction2011In: Vitamins in the prevention of human diseases / [ed] Wolfgang Herrmann and Rima Obeid, Berlin, Germany: De Gruyter , 2011, 1, p. 125-140Chapter in book (Refereed)
  • 10.
    Olsson, Lovisa A.
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine/Clinical Chemistry, Örebro University Hospital, Örebro, Sweden.
    Hagnelius, Nils-Olof
    Örebro University Hospital. Department of Geriatrics, Örebro University Hospital, Örebro, Sweden.
    Nilsson, Torbjörn K.
    Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden.
    Renal function is a determinant of subjective well-being in active seniors but not in patients with subjective memory complaints2014In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 7, no 1, article id 647Article in journal (Refereed)
    Abstract [en]

    Results: There were no significant differences in cystatin C and eGFR values between the two cohorts: cystatin C medians 0.88 vs 0.86 mg/L and eGFR 73 vs 80 mL/min/1.73 m2(AS vs DGM). In the AS cohort cystatin C was negatively related to PGWB index in women (P &lt; 0.001, R 2≈ 5%), and the covariates age and BMI did not improve the models. The renal biomarkers were unrelated to the PGWB index in the DGM cohort. Cystatin C in the AS cohort was adversely related to the PGWB subdimensions anxiety, depressed mood, positive well-being, and vitality in women, but in men only to depressed mood (P &lt; 0.006; R 2≈ 6%). In the DGM cohort, depressed mood in men was also significantly related to cystatin C (P = 0.050), but not in women.

    Background: During our whole life span, factors influencing health and functioning are accumulated. In chronic kidney disease, quality of life is adversely affected. We hypothesized that biomarkers of renal function could also be determinants of subjective well-being (SWB) in Swedish elderly subjects. SWB was assessed by the Psychological General Well-Being index (PGWB index) in two study groups: Active seniors (AS) consisted of community-dwelling elderly Swedes leading an active life (n = 389), and the DGM cohort (n = 300) consisted of subjects referred to the Memory Unit at the Department of Geriatrics for memory problems, Serum creatinine, cystatin C, and eGFR (CKD-EPI) were used as biomarkers of renal function.

    Conclusions: Renal function even within the normal range, measured by serum cystatin C concentration, has significant and sex specific associations with subjective well-being and its subdimensions in healthy elderly subjects. Maintenance of good renal function in aging may be of importance in maintaining a high subjective well-being.

  • 11.
    Olsson, Lovisa A.
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Hagnelius, Nils-Olof
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Olsson, Henny
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Nilsson, Torbjörn K
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Subjective well-being in Swedish active seniors or seniors with cognitive complaints and its relation to commonly available biomarkers2013In: Archives of gerontology and geriatrics (Print), ISSN 0167-4943, E-ISSN 1872-6976, Vol. 56, no 2, p. 303-308Article in journal (Refereed)
    Abstract [en]

    Well-being (WB) is a complex variable in its relation to physical health and other personal and social characteristics. The aim was to study subjective well-being (SWB) and its possible associations with traditional biomarkers of cardiovascular risk or dementia, in Swedish seniors. SWB was estimated by the Psychological General Well-Being (PGWB) index in two study groups. The active seniors (AS) group consisted of community-dwelling elderly Swedes leading an active life (n=389). The DGM cohort (n=300) consisted of subjects referred to the Memory Unit at the Department of Geriatrics, the cognitive problems had to be subjective, mild or moderate (MMSE≥10). There were differences in all six subdimensions of SWB or distress, and in the sum of PGWB scores, between the two study groups (p<0.001 for all), and adjustment for differences in biomarkers of somatic health (age, sex, blood pressure, BMI, HDL cholesterol, ApoB/ApoA1 ratio, creatinine, and homocysteine) did not attenuate these differences. In addition, cognition as assessed by the Clock-Drawing Test (CDT) showed independent associations with four of the PGWB subdimensions and with the PGWB sum. Among the subjects in the DGM cohort, SWB was equally low among subjects with an MCI (minor cognitive impairment) diagnosis or without a dementia diagnosis as among subjects diagnosed with dementia disorder. We conclude that the nosological grouping variable (AS vs. DGM cohort) and a cognitive factor were the main independent predictors of SWB in this sample of elderly Swedes, whereas biomarkers of somatic health played a subordinated role.

  • 12.
    Simonsen, A. H.
    et al.
    Memory Disorders Research Group Section 6702, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Köpenhamn, Denmark.
    Hagnelius, Nils-Olof
    Department of Geriatric Medicine, Örebro University Hospital, Örebro, Sweden.
    Waldemar, G.
    Memory Disorders Research Group Section 6702, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Köpenhamn, Denmark.
    Nilsson, T. K.
    Department of Laboratory Chemistry, Örebro University Hospital, Örebro, Sweden.
    McGuire, J.
    Department of Incretin Biology, Novo Nordisk, Gentofte, Denmark.
    Protein markers for the differential diagnosis of vascular dementia and Alzheimer's disease2012In: International Journal of Proteomics, ISSN 2090-2166, E-ISSN 2090-2174, Vol. 2012, article id 824024Article in journal (Refereed)
    Abstract [en]

    Alzheimer's disease (AD) is the most common form of dementia found in all human populations worldwide, while vascular dementia (VaD) is the second most common form of dementia. New biomarkers for early and specific diagnosis of AD and VaD are needed to achieve greater insight into changes occurring in the brain and direct therapeutic strategies. The objective of this explorative study was to discover candidate protein biomarkers for the differential diagnosis between VaD and AD. Surface-enhanced laser desorption/ionization (SELDI) TOF-MS was used to differentially profile proteins and peptides in CSF samples from 28 AD patients and 21 patients with VaD. A combination of univariate (Kruskal-Wallis) and multivariate (independent component analysis) statistical approaches produced a list of 27 proteins and peptides that could differentiate between VaD and AD. These markers represent various physiological processes, such as protein degradation (ubiquitin), protease inhibition (cystatin C and alpha-1-antichymoptrypsin), and inflammation (C3a and C4a) that are known to be represented in neurodegenerative diseases.

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