Gene Linked to High Homocysteine, Lower Cognitive Performance

Newswise — Scientists have established a link between high levels of the amino acid homocysteine in the blood and lower cognitive performance. Now, new work by three University of Maine researchers provides evidence that the presence of a particular variant of a neuron repairing gene may increase the risk of lowered cognitive performance.

UMaine psychology professors Merrill F. "Pete" Elias, Michael A. Robbins and Penelope K. Elias, in collaboration with colleagues in Syracuse, N.Y., England and Australia, studied the relationships among the gene ApoE, homocysteine concentrations, and cognitive performance.

They found that stroke and dementia-free people with higher homocysteine levels, in addition to carrying one or more of the ApoE-ε4 alleles, performed at lower levels on multiple measures of cognition than people with other variations of the ApoE-ε4 gene. An allele is any one of several possible gene variants. The subjects were part of the ongoing "Maine-Syracuse Study," involving more than 2,700 people since begun in 1974.

Robbins and the Eliases, professors in the department of psychology at the University of Maine, and their co-researchers reported their findings in an article published in the January 2008 issue of Neuroscience Letters, a peer-reviewed science journal.

"The importance of our recent paper in Neuroscience Letters is that we find that the combination of elevated homocysteine and the presence of the ApoE-ε4 allele represent a higher degree of risk for lower cognitive performance than the presence of either risk factor alone," says Merrill Elias.

Elias notes that carriers of the ApoE-ε4 allele "might be thought of as having a less effective neuronal repair capability. There currently is no practical way that one can modify the ApoE-ε4 alleles so that they do a better job of repairing brain cells," he says. "But there is hope for prevention and reversal of cognitive deficit related to elevated homocysteine by reducing homocysteine levels."

Vitamin supplementation " the focus of earlier research by Robbins and the Eliases " may be among the important ways of achieving these goals, Robbins adds.

In an article published in 2006 in Psychosomatic Medicine, the Eliases, Robbins and colleagues " using a comprehensive analysis controlling differences in age, education, gender, ethnicity, medications and cardiovascular disease " reported that higher folate, Vitamin B6 and Vitamin B12 levels are related to better cognitive performance. Many clinical trials in the United States, Europe and elsewhere currently are examining the possibility that lowering homocysteine with these vitamins may reverse homocysteine-related cognitive deficits, including dementia.

"Testing for homocysteine concentrations is easily performed but it is not a common practice in medicine today," Merrill Elias says. "Tests of folate, Vitamin B6, and Vitamin B12 are sometimes done when deficits are suspected, but hopefully these tests, including tests for homocysteine level, will eventually be done routinely."

Robbins adds that this is especially important for older people to be aware of vitamin levels. "They might seem to take in enough B6 and B12 vitamins, but they may not metabolize them well," he says.

Given the evidence about ApoE-ε4, homocysteine, cognitive function and cardiovascular disease risk, the Eliases and Robbins suggest a proactive approach to vitamin supplements, but caution that more is not always better. To avoid overdosing, a physician or nutritionist should be consulted to establish appropriate dosing levels.

The study is part of an ongoing research project that Merrill Elias and D.H.P. Streeten, M.D., began in 1974 when Elias was an associate professor of psychology at Syracuse University. The estimated 2,700 participants in the study are followed all over the country, including Maine and Syracuse, for testing at five-year intervals. The project now is based at UMaine with Elias.

The paper in Neuroscience Letters, titled "Homocysteine and Cognitive Performance: Modification by the ApoE Genotype," is the latest in a series of many journal articles Robbins and the Eliases have coauthored on aging, cardiovascular disease and cognition with research support from the National Institute on Aging and the National Heart Lung and Blood Institutes of the National Institutes of Health.

The associated projects were supported by research grants from the National Heart, Lung and Blood Institute and the National Institute on Aging. The content of published papers is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung and Blood Institute or the National Institutes of Health.