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High homocysteine and methylmalonate among demented and non-demented elderly receiving vitamin-B12 prescription and home help service
Örebro University, School of Health and Medical Sciences.ORCID iD: 0000-0002-2869-7239
Karolinska Institutet, Neurotec.
Örebro University, School of Health and Medical Sciences.
(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 [en]
homocysteine, dementia, vitamin-B12, folate, home help service
National Category
Geriatrics Medical and Health Sciences
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-7842OAI: oai:DiVA.org:oru-7842DiVA, id: diva2:234426
Available from: 2009-09-09 Created: 2009-09-08 Last updated: 2017-10-18Bibliographically approved
In thesis
1. Vascular mechanisms in dementia with special reference to folate and fibrinolysis
Open this publication in new window or tab >>Vascular mechanisms in dementia with special reference to folate and fibrinolysis
2009 (English)Doctoral 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.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2009. p. 65
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 33
Keywords
dementia, Alzheimer’s disease, vascular dementia, folate, homocysteine, vitamin B12, CSF/Serum folate ratio, fibrinolysis, tPA, PAI-1
National Category
Geriatrics Medical and Health Sciences
Research subject
Geriatrics; Medicine
Identifiers
urn:nbn:se:oru:diva-7785 (URN)978-91-7668-682-9 (ISBN)
Public defence
2009-10-06, Bohmanssonsalen, Universitetssjukhuset Örebro, Örebro, 09:00 (English)
Opponent
Supervisors
Available from: 2009-09-02 Created: 2009-09-01 Last updated: 2017-10-18Bibliographically approved

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