1. |
- Hagnelius, Nils-Olof, 1953-, et al.
(author)
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Blood concentrations of homocysteine and methylmalonic acid among demented and non-demented Swedish elderly with and without home care services and vitamin B(12) prescriptions
- 2012
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In: Dementia and Geriatric Cognitive Disorders Extra. - Basel, Switzerland : S. Karger. - 1664-5464. ; 2:1, s. 387-399
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Journal article (peer-reviewed)abstract
- 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.
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2. |
- Hagnelius, Nils-Olof, 1953-, et al.
(author)
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High homocysteine and methylmalonate among demented and non-demented elderly receiving vitamin-B12 prescription and home help service
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Other publication (other academic/artistic)abstract
- 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.
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3. |
- Hagnelius, Nils-Olof, 1953-, et al.
(author)
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Fibrinolysis and von Willebrand factor in Alzheimer's disease and vascular dementia : a case-referent study
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Other publication (other academic/artistic)abstract
- 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.
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4. |
- Hagnelius, Nils-Olof, 1953-
(author)
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Vascular mechanisms in dementia with special reference to folate and fibrinolysis
- 2009
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Doctoral thesis (other academic/artistic)abstract
- 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.
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5. |
- Nilsson, Torbjörn, K., 1956-, et al.
(author)
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Folate in dementia and cognitive dysfunction
- 2011. - 1
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In: Vitamins in the prevention of human diseases. - Berlin, Germany : De Gruyter. - 9783110214499 ; , s. 125-140
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Book chapter (peer-reviewed)
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6. |
- Olsson, Lovisa A., 1950-, et al.
(author)
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Renal function is a determinant of subjective well-being in active seniors but not in patients with subjective memory complaints
- 2014
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In: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 7, s. 647-
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Journal article (peer-reviewed)abstract
- 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.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 < 0.001, R2 ≈ 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 < 0.006; R2 ≈ 6%). In the DGM cohort, depressed mood in men was also significantly related to cystatin C (P = 0.050), but not in women.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.
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7. |
- Olsson, Lovisa A., 1950-, et al.
(author)
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Subjective well-being in Swedish active seniors or seniors with cognitive complaints and its relation to commonly available biomarkers
- 2013
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In: Archives of gerontology and geriatrics (Print). - : Elsevier BV. - 0167-4943 .- 1872-6976. ; 56:2, s. 303-308
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Journal article (peer-reviewed)abstract
- 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.
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8. |
- Simonsen, A. H., et al.
(author)
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Protein markers for the differential diagnosis of vascular dementia and Alzheimer's disease
- 2012
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In: International Journal of Proteomics. - New York, USA : Hindawi Publishing Corporation. - 2090-2166 .- 2090-2174. ; 2012
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Journal article (peer-reviewed)abstract
- 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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