The research, led by Mary Haan from the University of Michigan, followed 1405 older Mexican Americans and found that increased levels of the amino acid homocysteine doubled the risk of dementia or cognitive impairment.
Higher levels of vitamin B12 were associated with lower homocysteine levels, adding to previous studies reporting that B12 may be the more important than the other B vitamins for determining homocysteine levels and subsequently the risk of dementia.
Epidemiological studies have reported that high levels of the amino acid homocysteine are associated with suspected or confirmed dementia. Indeed, the Framingham study reported that people with homocysteine levels above 14 micromoles per litre of serum had twice the risk of dementia.
This has led to the hypothesis that by lowering circulating levels of homocysteine by B vitamin supplements, the risk and occurrence of dementia could be reduced. However, intervention trials have reported mixed results, and the subject remains debatable.
The new study, published in the current issue of the American Journal of Clinical Nutrition, is epidemiological and adds support to the observation that higher blood levels of vitamin B12 are associated with lower homocysteine levels, which in turn are linked to a lower risk of cognitive decline and dementia.
Over 4.5 years of follow-up, 4.4 per cent of 1405 participants developed dementia, and 3.9 per cent of participants developed cognitive impairment with no dementia (CIND).
Elevated baseline homocysteine (13 micromoles per litre or more) increased the risk of developing dementia or CIND by 136 per cent. The risk of cognitive decline further increased in subjects with both low vitamin B-12 and elevated homocysteine concentrations.
Folate levels, calculated from red blood cells, were not associated with homocysteine levels or cognitive impairment, but the authors noted that folic acid fortification in the US food supply, introduced before the start of this study, probably eliminated low folate values in their cohort..
"Findings from the Framingham Study, and the current study, both of which have longer follow-up times, suggest that homocysteine may be an independent predictor of dementia outcomes. The role of vitamin B12 in dementia risk should be further evaluated," concluded Haan.
In an accompanying editorial, Robert Clarke from the University of Oxford said the research was important for three reasons.
"First, Haan et al provide evidence that the associations of dementia or cognitive impairment with elevated homocysteine may be explained by reduced vitamin B12 status rather than reduced folate status.
"Second, the U-shaped association of dementia and cognitive impairment with vitamin B12 may be an artefact, but, if real, it may add to previously reported concerns about the safety of mandatory folic acid fortification in older people with vitamin B12 deficiency.
"Third, if Haan et al had measured plasma holotranscobalamin (the active fraction of vitamin B12) or methylmalonic acid (specific metabolite of vitamin B12), rather than total vitamin B12, they may have found stronger associations of dementia or cognitive impairment with impaired vitamin B12 status than those reported in the current study."
Dr Clarke also said that vitamin B12 is a more important determinant of high homocysteine levels in people over 70 than folate, and that future studies should focus on dietary supplementation of one milligram of B12 in elderly people to investigate cognitive decline.
The B-Vitamin Treatment Trialists' Collaboration should soon be better able to address the link between B-vitamins, homocysteine levels, and cognitive function. The effects of three to seven years of treatment with B vitamins on cognitive function should eventually be available on about 20,000 of the 50,000 participants with previous cardiovascular or renal disease from 12 large homocysteine-lowering trials.
Alzheimer's is the most common form of dementia and currently affects over 13 million people worldwide. By the year 2047, the prevalence of Alzheimer's disease (AD) is expected to quadruple.
Source: American Journal of Clinical Nutrition February 2007, Volume 85, Pages 511-517 "Homocysteine, B vitamins, and the incidence of dementia and cognitive impairment: results from the Sacramento Area Latino Study on Aging" Authors: M.N. Haan, J.W. Miller, A.E. Aiello, R.A. Whitmer, W.J. Jagust, D.M. Mungas, L.H. Allen, R. Green
Editorial: American Journal of Clinical Nutrition February 2007, Volume 85, Pages 329-330 " Homocysteine, B vitamins, and the risk of dementia" Author: R. Clarke