A search for clues

Scientists searching for clues to the causes of age-related dementia suspect that a combination of high serum homocysteine and low serum folate has an unhealthy impact on cognitive function in seniors. A study supporting this theory was published recently in the American Journal of Clinical Nutrition.

Tufts University scientists analyzed data collected on about 1,200 participants of the third National Health and Nutrition Examination Survey (NHANES III) conducted in the United States from 1991-1994. All participants were over age 60 with no history of stroke, and all had at least 8 years of education. Available information included extensive demographic data and serum values for a range of key nutrients, lipids, and homocysteine. As part of the survey process, participants completed 2 tests of short-term memory - recall of three words and recall of 6 key points of a short story.

B vitamins linked to memory

After controlling for potential confounders (age, gender, race, education, and income) researchers found that those with high serum folate levels were better able than those with low levels to recall story details (P<0.001). Looking only at those with low folate levels, participants with serum homocysteine levels higher than the 80th percentile (>13.7 mmol/L) were less able than those with lower serum values to recall story details (P<0.03). And those with the highest homocysteine levels, regardless of folate status, were more likely than those with lower homocyteine levels to score below average on the word recall test (Odds Ratio = 0.3, 95% CI = 0.2-0.7).

Regardless of homocysteine and folate status, the average participants' memory skills declined with age. The odds ratio of those over age 70 unable to recall more than 3 story details, as compared with younger participants, was 2.6 (95% CI = 1.9-3.5).

Several possible pathways

The authors acknowledge that not all of the research in this area supports a connection between homocyteine and folate status and cognition - an earlier analysis of NHANES III data found no association between serum folate and short-term memory, for instance. Nevertheless, several possible biological pathways could explain such a link.

Hyperhomocysteinemia has been associated with an increased risk of both stroke and Alzheimer's disease, reinforcing a suspected link between vascular disease and age-related memory loss. Also, some scientists suspect a causal relationship between low folate levels and memory loss independent of homocysteine status, since folate is a component in cofactors needed for neurotransmitter metabolism.

More study needed

The results of this study show a correlation between elevated levels of homocysteine and reduced cognitive function, a relationship that appears to a certain degree to be independent of folate status. The study's authors emphasize, though, that memory impairment is likely due to multiple factors, with homocysteine and folate concentrations being two such variables.

It is premature to assume that folic acid supplementation will prove to be the preventive step that clinicians are looking for to reduce the risk of age-related memory loss, but it is an option that merits a closer look. The authors point out that it will be interesting to see if the recent addition of folic acid to nutrient-fortified grain foods in the United States, with its possible homocysteine-lowering effect, has a favorable effect on memory function in seniors.