Elevated homocysteine levels may increase risk of Alzheimer's disease
What is homocysteine and why would it increase your risk of Alzheimer's disease? Homocysteine is a building block of protein that is produced in the human body. However, too much homocysteine in the bloodstream can lead to blood vessel damage and blockage of the arteries. For this reason, elevated homocysteine levels are considered a risk factor for vascular diseases such as coronary heart disease and stroke. Finally, research in the last decade has unearthed a possible connection between vascular diseases and the risk of Alzheimer's disease and other forms of dementia. Now a study recently published in The New England Journal of Medicine suggests that elevated homocysteine levels in and of themselves may increase an older person's risk of Alzheimer's disease and other dementias.
About the study
Between 1986 and 1990, researchers at Boston University and Tufts University in Boston began studying a subgroup of participants in the Framingham Study—a large, ongoing study of disease incidence among adults in Framingham, Massachusetts. Framingham participants have been undergoing complete physical exams and answering lifestyle questionnaires every two years since the study's inception in 1948. Specifically, the 1092 men and women (average age 76) in this smaller study were all free of dementia at their 20th biennial exams, which occurred between 1986 and 1990. At this exam and the 16th biennial exam (approximately 8 years earlier), blood homocysteine levels were also measured.
In addition to the physical exam, questionnaires, and medical tests involved in the Framingham Study protocol, participants in this study underwent a few more tests. During each biennial exam from 1986 to December 31, 2000, participants underwent tests for dementia, which were evaluated by two neurologists and a neuropsychologist. In addition, they were tested for an apolipoprotein E gene that is a known risk factor for Alzheimer's disease.
Researchers reviewed the participants' medical records from the 20th biennial exam (the start of this study) through December 31, 2000, as well as their homocysteine measurements from the 16th biennial exam. In particular, they were looking at how blood levels of homocysteine correlated with Alzheimer's disease or other dementias.
After accounting for other risk factors for Alzheimer's disease and other dementias, people with the highest levels of homocysteine had nearly twice the risk of Alzheimer's disease and other dementias as people with lower homocysteine levels. Specifically, an increase of 5 micromoles of homocysteine per liter of blood increased the risk of Alzheimer's disease by 40%.
Of interest, these statistics were true of homocysteine levels from both the 16th and 20th biennial exams. This is important, because Alzheimer's disease develops slowly and it's possible that the disease process had begun in some participants at the 20th biennial exam but was not yet detectable. However, it's very likely that the participants were truly free of disease 8 years earlier at the 16th biennial exam.
There are limitations to this study, however. The vast majority of participants in this study were white, meaning that these results may not apply to people of other racial groups. In addition, the participants were not required to fast before the homocysteine blood tests, which may have caused the homocysteine levels to be up to 20% higher than if they had fasted. However, this was true for all participants, so any variation is not likely to have affected the results. Finally, these findings do not explain the mechanism by which homocysteine might cause an increase in Alzheimer's disease and other dementias.
How does this affect you?
Are elevated blood levels of homocysteine a predictor of Alzheimer's disease? It's too soon to say. We already know that elevated homocysteine levels may increase your risk of heart disease and stroke. Now these findings suggest that elevated homocysteine levels may also increase your risk of Alzheimer's disease and other dementias as you age. But they don't prove that elevated homocysteine levels are an indicator of future Alzheimer's disease. And because participants' ages ranged from 68 to 97, it's not clear whether younger adults with high homocysteine levels are at increased risk of Alzheimer's disease later in life.
Regardless of Alzheimer's risk, evidence from several studies suggests that maintaining healthy homocysteine levels may help prevent blood vessel damage and atherosclerosis (hardening of the arteries). How can you keep your homocysteine levels in the normal range? Folic acid and vitamin B12 in food or supplement form are known to reduce homocysteine levels in the blood. What is not yet known, the study authors caution, is whether increased intake of these nutrients reduces the risk of Alzheimer's disease and other dementias. But it doesn't hurt to eat a healthful diet that includes adequate amounts of folic acid and vitamin B12.
Foods containing folic acid include:
- Fruits and orange juice from concentrate
- Green, leafy vegetables
- Dried beans and legumes
- Breads products that have been fortified with folic acid, such as cereal, pasta, rice, and bread
Foods containing vitamin B12 include:
- Liver and other meats such as pork and beef
- Milk and other milk products
Seshadri S, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease.
New England Journal of Medicine . February 14, 2002;346(7):476-483.
Loscalzo J. Homocysteine and dementias.
New England Journal of Medicine . February 14, 2002;346(7):466-468.
Last reviewed Feb 14, 2002 by
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