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S1–01–01: Homocysteine: Causal risk factor or prognostic marker?
Author(s) -
Smith David
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.006
Subject(s) - dementia , homocysteine , medicine , prospective cohort study , cognition , cognitive decline , risk factor , psychiatry , disease
Background: Moderately raised levels of plasma total homocysteine (tHcy) and low-normal levels of folate and vitamin B12 were first reported in 1998 to be associated with both pathologically-confirmed AD and VaD. Objective(s): Review evidence from cross-sectional and prospective studies that has accrued since 1998 concerning tHcy, dementia and cognitive deficit. Consider the biological plausibility for a causal role. Methods: PubMed search until end of 2005. Conclusions: Seventy-six cross-sectional studies involving 33,892 subjects have reported associations between dementia or cognitive deficit and raised tHcy and/or low B vitamin blood levels, while 7 studies involving 3645 subjects failed to find an association. Three studies found that about 10% of the variance in cognitive test scores in normal elderly can be accounted for by the level of tHcy. Twelve prospective studies involving 6661 subjects reported an association between raised blood levels of tHcy and subsequent dementia or cognitive decline. Three studies involving 1722 subjects failed to find a prospective association. No valid randomized clinical trials of homocysteine-lowering treatments have been reported, but one study in Norway on 1670 elderly community subjects showed that in those whose tHcy level fell over a 6-year period the final episodic memory test score was higher than in those whose tHcy remained the same, while in those whose tHcy level increased over 6 years, the final test score was lower. Biological plausibility for a causal role of tHcy is shown by several reports, three prospective, of an association between raised tHcy levels and atrophy of medial temporal lobe structures or whole brain. At the cellular level, homocysteine has a variety of effects on the cerebral vasculature and on neurons. Direct neurotoxicity has been shown as well as potentiation of beta-amyloid toxicity and of excitotoxicity. We can conclude that raised tHcy is a strong prognostic marker for brain atrophy and for cognitive decline and dementia, but evidence of a direct causal role awaits the result of clinical trials. It is hoped that one such trial will have reported by the time of the meeting. S1-01-02 GLUCOCORTICOID RECEPTOR GENE VARIANT AND RISK OF DEMENTIA AND WHITE MATTER LESIONS