Vitamin B-12 and folate status in relation to decline in scores on the Mini-Mental State Examination in the Framingham Heart Study

Authors: MORRIS, MARTHA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SELHUB, JACOB - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; JACQUES, PAUL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of the American Geriatrics Society
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/27/2012
Publication Date: 8/1/2012
Citation: Morris, M.S., Selhub, J., Jacques, P.F. 2012. Vitamin B-12 and folate status in relation to decline in scores on the Mini-Mental State Examination in the Framingham Heart Study. Journal of the American Geriatrics Society. 60(8):1457-1464.

Interpretive Summary: Low vitamin B-12 status is known to be related to poor mental functioning – like forgetfulness or a difficulty learning new information or performing complex mental tasks. We all become more deficient in vitamin B-12 as we age. This is due to the aging of our gastrointestinal systems. We also become prone to poor mental functioning, Alzheimer’s disease, and other forms of dementia as we age. The simultaneous occurrence of these two age-related trends raises the hypothesis that they are causally related. One problem with trying to find out whether the two trends are causally related is uncertainty about how to identify people with low vitamin B-12 status. Most often, the level of vitamin B-12 in the blood is used, but the proper cut-off point to separate low from normal is unclear. In this study, we used data collected on 549 participants in the Framingham Heart Study (mean age 74.8±4.6), and divided them into 5 categories. Each category contained 20% of the participants (or about 110 people), but each successive category had a higher range of plasma vitamin B-12 levels than the previous one. The subjects had been administered the Mini-Mental State Examination (MMSE) at each of their physical examinations, which had occurred every two years for eight years. The MMSE is a crude dementia screening test that can distinguish people with gross mental deficiency from people who have maintained normal mental functioning into older age. We found that the 40% of the subjects with the lowest plasma vitamin B-12 levels (that is subjects in the first two of the five categories) were prone to accelerated deterioration in their mental functioning. In other words, the data suggest that 40% of seniors are at risk of becoming demented due to their low vitamin B-12 status. This is much higher than previous estimates of clinically significant low vitamin B-12 status, which were based on risk of anemia, rather than risk of dementia. These findings will help physicians identify seniors in their medical practices who are at risk of becoming demented due to vitamin B-12 deficiency. This will benefit seniors, because, once identified, they can be treated with vitamin B-12 to prevent deterioration in mental functioning. It is important to note that vitamin B-12 deficiency is just one cause of the deterioration in mental functioning that occurs with age, so identifying and treating low vitamin B-12 status will not prevent all dementia. In fact, the most common form of age-related dementia is Alzheimer’s Disease, and there is little evidence that vitamin B-12 deficiency is involved in that disease, or that treating people who have Alzheimer’s Disease will be helpful.

Technical Abstract: Biochemical evidence of low vitamin B-12 status is common in seniors, but its clinical relevance is unclear. Vitamin B-12 deficiency can result in rapid, irreversible cognitive decline – a phenomenon that has been linked to high folate status. Our objective was to investigate the cognitive significance of low to low-normal plasma vitamin B-12 concentrations. Secondarily, we sought to shed light on the role that folate status plays in the association between vitamin B-12 status and cognitive decline. Using data from The Framingham Heart Study, a prospective epidemiologic study, we evaluated associations between plasma vitamin B-12 and folate and 8-year cognitive decline. We also assessed interactions between vitamin B-12 status and both folate status and supplemental folate use in relation to cognitive decline. The subjects were 549 community-dwelling seniors (mean age 74.8 +/- 4.6) who were administered the Mini-Mental State Examination (MMSE) and whose body mass index and plasma levels of folate, vitamin B-12, methylmalonic acid, and homocysteine were measured assessed. MMSE scores declined by 0.24 points/year over the 8-year follow-up period. Decline was significantly accelerated among cohort members in the bottom two plasma vitamin B-12 quintile categories, and no apparent cognitive advantage was associated with plasma vitamin B-12 from 187-256.8 pmol/L versus less than or equal to 86 pmol/L. Among cohort members with plasma vitamin B-12<258 pmol/L, plasma folate greater than or equal to 20.2 nmol/L or supplemental folate use was associated with an approximate 1-point/year decline. We conclude that plasma vitamin B-12 from 187-256.8 pmol/L is cognitively significant. Furthermore, high plasma folate and supplemental folate use identify subgroups in this vitamin B-12 range and below who are prone to especially rapid cognitive decline.