A new study in The New England Journal of Medicine edges scientists a little closer to learning why Alzheimer's disease develops in some aging brains and not in others. Boston researchers analyzed data from the long-running Framingham Study, and demonstrated a correlation between high blood levels of homocysteine and an increased risk of Alzheimer's disease.

A closer look at the data

Blood homocysteine levels were measured on more than 1,000 elderly participants determined to be free of dementia during the 1986-1990 follow-up period. The men and women were tracked for up to 8 years, or until diagnosis of dementia.

The researchers found that the risk of dementia rose with increasing homocysteine levels. Adjusted for age, sex, and ApoE genotype, the relative risk of Alzheimer's disease was 1.4 for each increase of 1 SD in log-transformed homocysteine values (95% CI=1.2-1.7). The 30% of participants with high homocysteine levels -- above 14 micromoles/liter -- were almost twice as likely as others in the study to develop Alzheimer's disease (RR=1.9; 95% CI, 1.2-3.0). Adjustments for serum levels of folate, B12, and B6 did not significantly alter the results.

What's the connection?

Elevated homocysteine levels are associated with carotid atherosclerosis and risk of stroke. Both, in turn, are linked to an increased risk of Alzheimer's disease. The exact pathway is not yet clear, but high homocysteine levels have been associated with cerebral microangiopathy, endothelial dysfunction, and increased oxidative stress, all of which contribute to aging of the brain.

Supplemental doses of certain B vitamins -- folic acid, B12, and B6 -- can lower blood homocysteine levels by facilitating its conversion to methionine. Homocysteine levels naturally rise with age, though, and scientists are not yet sure if supplemental doses of B vitamins can help seniors keep their homocysteine levels consistently low enough to sidestep the accumulating blood vessel damage that likely contributes to the development of Alzheimer's disease.

Even with some questions still to be answered, the researchers note that homocysteine levels in the Framingham Study participants have steadily dropped in the five years since the US began fortifying grain foods with folic acid. It's too early to tell if that has made a significant dent in the incidence of dementia in this aging population, but scientists are focusing on the homocysteine-lowering potential of the B vitamins, especially folic acid.

Advice to patients

Homocysteine testing isn't routinely included in most health check-ups, although some physicians believe that, along with cholesterol testing, it's a good way to assess cardiovascular health.

What about vitamin supplements? It's not yet clear if higher intakes of B vitamins now would lead to less risk of dementia later on, and it's also not known how much of each vitamin would be needed to provide maximum benefit. Older patients who consume a limited diet may want to consider adding a multivitamin that includes 100% of the RDA of folic acid, B6, and B12 to their daily routine. It can't hurt, and it may help keep harmfully high levels of homocysteine in check.