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Heart Disease Marker Now Tied to Alzheimer's

Study finds high homocysteine levels in blood double risk of dementia

WEDNESDAY, Feb. 13, 2002 (HealthDayNews) -- Large elevations in a blood molecule linked to heart disease also appear to double the risk of developing Alzheimer's disease and dementia.

A new study shows homocysteine is crucial for many of the body's biochemical processes, and its levels increase with age. However, the findings, which appear in tomorrow's issue of the New England Journal of Medicine, also show that abnormally high levels of the molecule, and large increases over time, strongly predict who will develop dementia.

Taking folic acid and B vitamins can lower homocysteine, experts say, though there's no evidence yet to suggest these dietary measures can also reduce the risk of cognitive problems. However, researchers are now studying whether taking supplements can slow cognitive loss in those with mild and moderate Alzheimer's.

"We don't have that many risk or protective factors for Alzheimer's disease," says Neil Buckholtz, a dementia expert at the National Institute on Aging, which funded the latest study. "Age is still the major risk factor that we know about, which is clearly not modifiable."

A group led by Dr. Sudha Seshadri, a Boston University neurologist, looked at 1,092 men and women who started a large study without cognitive problems.

The subjects, whose average age was 76, were enrolled in an ongoing research project called the Framingham Heart Study. Begun in the 1940s, Framingham gave Seshadri and her colleagues access to blood samples taken between 1979 and 1982, and again between 1986 and 1990.

Over roughly eight years of follow-up, 111 of the subjects developed dementia, including 83 who were diagnosed with Alzheimer's. After accounting for the effects of age and other factors, those with elevated homocysteine levels at the second reading had about twice the risk of dementia as subjects with normal readings for the substance, the researchers say.

From earlier research, it was impossible to tell if elevated homocysteine levels predicted or simply reflected brain disease.

"I think we have helped show that the homocysteine levels increase well before the onset of clinical dementia," Seshadri says.

Not all dementia is related to Alzheimer's; some results from vessel damage and other illnesses. However, the researchers found that elevated homocysteine appeared to boost the risk of cognitive problems associated with both the degenerative brain disorder and other forms of cognitive loss, Seshadri says.

Seshadri's group is now measuring current homocysteine levels in their subjects to see if the increase persists in those with dementia. They are also testing the children of Framingham study participants for the compound, and plan to compare those results to scores on cognitive tests and readings on brain scans.

As for why high homocysteine levels might be linked to brain disease, "nobody really knows," Seshadri says.

Dr. Paul Aisen, a Georgetown University neurologist who's leading the trial on vitamins, says some scientists have speculated homocysteine might promote dementia by damaging blood vessels that feed the brain. However, recent evidence suggests too much of the molecule can directly harm brain cells, too.

Although Seshadri's study looked only at the impact of abnormally high homocysteine levels, Aisen says some evidence indicates that even slight elevations in the molecule might be detrimental.

"We hypothesize that the lower the homocysteine levels the better," he says.

In his study, Aisen and his colleagues will give folic acid and vitamins B12 and B6 to 400 Alzheimer's patients for 18 months.

"Our hypothesis is that by lowering homocysteine, we will slow down the progression of Alzheimer's," he says.

What To Do

To find out more about homocysteine and the blood vessels, check out the American Academy of Family Physicians or the American Heart Association.

Alzheimer's disease, which is thought to be caused by buildup in the brain of protein plaques, affects an estimated 4 million Americans. However, the number of patients is expected to swell as the population ages. For more on the degenerative disorder, try the Alzheimer's Association.

SOURCES: Interviews with Sudha Seshadri, M.D., neurologist, Framingham Heart Study, assistant professor, department of neurology, Boston University School of Medicine, Boston; Neil Buckholtz, Ph.D., chief, dementias of aging branch, National Institute on Aging, Bethesda, Md.; Paul Aisen, M.D., professor, neurology and medicine, Georgetown University Medical Center, Washington, D.C.; Feb. 14, 2002, New England Journal of Medicine
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