Amino Acid Linked to Higher Alzheimer’s Risk
Elevated levels of a specific amino acid in the blood appear to increase by as much as twofold a person’s risk of developing Alzheimer’s disease, researchers reported Wednesday.
The findings suggest there may, for the first time, be a way to identify people who are at increased risk of the disease and can do something about it, as blood levels of the substance, called homocysteine, can be easily lowered by taking certain vitamin supplements.
“It’s like cholesterol--too much is bad,” said Boston University neurologist Sudha Seshadri, who conducted the new research published in Thursday’s New England Journal of Medicine. “We don’t know exactly how much is the optimal amount, but it seems that over a wide range, the more you have, the worse it is.”
Previous research has revealed a similar association between high homocysteine and the risk of heart attack and stroke. While no studies have shown that lowering homocysteine prevents disease, clinical trials testing that hypothesis for heart attacks and stroke are underway. Such trials for Alzheimer’s will probably now be proposed as well.
“This points us in a testable direction [toward preventive measures], and that’s a significant step forward, no doubt about it,” said Bill Thies, vice president for medical and scientific affairs at the Alzheimer’s Assn., an advocacy group headquartered in Chicago.
The most common cause of dementia, Alzheimer’s affects about 4 million Americans. By age 65, about 5% of people are afflicted with the disease. The prevalence rises to about 15% at age 75, and to as high as 45% by age 85, according to some studies. The disease has a relentlessly downhill course, although there’s a relatively long survival after diagnosis, about seven years.
The search for modifiable risk factors for Alzheimer’s has been intense because there’s nothing people can do about the three risk factors for the disease identified previously: age, family history and presence of a specific genetic trait called APOE epsilon 4.
In the new study, Seshadri and several colleagues used data from the Framingham Heart Study, in which several thousand people--all residents of a town outside Boston and almost all of them white--have been examined and subjected to various medical tests every other year since 1948.
In the late 1980s, homocysteine levels were measured in about 1,100 study participants whose average age was about 75, none of whom were demented. By eight years later, 10% had developed dementia, most of it attributable to Alzheimer’s (as opposed to stroke or other vascular disease).
The 30% of people with the highest homocysteine levels had twice the risk of developing Alzheimer’s disease as people with average levels, although even mild elevations appeared to add some risk.
The findings held even when the researchers used statistical methods to control for other things that may contribute to dementia risk or ill health in old age, such as educational status, blood pressure, smoking, alcohol intake, and presence of diabetes or previous stroke.
Elevated homocysteine accounted for about 15% of the population’s risk for Alzheimer’s disease. That means that if homocysteine were entirely removed from the complicated risk equation, 15% of cases would be prevented. In contrast, the APOE epsilon 4 genetic trait is somewhat more powerful, accounting for about 20% of risk.
There’s a complicated and poorly understood link between vascular disease and Alzheimer’s. For example, it’s widely known that some people who suffer a stroke rapidly develop dementia. Recent research suggests that occurs mostly in people who already have mild, often unrecognized, memory loss. Stroke seems to unmask, or accelerate, their Alzheimer’s.
The new findings show that, regardless of the relationship that may exist between homocysteine and vascular disease, it appears to affect Alzheimer’s in some way. It’s possible that homocysteine is toxic to brain cells, possibly by stimulating them excessively.
