February 20, 2002
High Homocysteine Levels May Double
Risk of Dementia, Alzheimer’s Disease, New Report Suggests
People with elevated levels of homocysteine in the blood had nearly double
the risk of developing Alzheimer's disease (AD), according to a new report
from scientists at Boston University. The findings, in a group of people
participating in the long-running Framingham Study, are the first to tie
homocysteine levels measured several years before with later diagnosis of AD
and other dementias. The report, which appears in the February 14, 2002,
issue of The New England Journal of Medicine, provides some of the most
powerful evidence yet of an association between high plasma homocysteine and
later, significant memory loss.
The relationship between AD and the amino acid homocysteine is of particular
interest because blood levels of homocysteine can be reduced, for example,
by increasing intake of folic acid (or folate) and vitamins B6 and B12. The
therapeutic use of these compounds is being explored as scientists try to
understand better homocysteine's role in AD or other types of dementia as
well as its possible link to various forms of heart disease.
The dementia/AD study is being conducted by Philip A. Wolf, M.D., Boston
University (BU), and colleagues at BU and Tufts University, who authored the
new findings. The study was supported by the National Institute on Aging
(NIA), part of the National Institutes of Health (NIH). The researchers were
also funded by NIH's National Institute of Neurological Disorders and Stroke
(NINDS). The Framingham Heart Study is supported by the NIH's National
Heart, Lung, and Blood Institute (NHLBI).
"The Framingham population gave us the perfect opportunity to look at
homocysteine levels in a group of people without memory problems over a
period of several years, well before any evidence of dementia," Wolf pointed
out. "This is the clearest demonstration yet of the relationship between
elevated homocysteine levels and dementia," he noted.
"The evidence is beginning to mount regarding homocysteine's role in
dementia," according to Neil Buckholtz, Ph.D., chief of the Dementias of
Aging program at the NIA. "The good news is that we may have found a
potential risk factor for AD that is modifiable. We don't know yet whether
reducing homocysteine levels will reduce dementia risk, but this is
something that can and will be tested in clinical trials." Buckholtz noted
that the NIA-sponsored Alzheimer's Disease Cooperative Study, a nationwide
consortium of research centers, is already planning a clinical trial of
folate and vitamins B6 and B12 to test whether reducing homocysteine levels
with high doses of these vitamin supplements can slow the rate of cognitive
decline in people diagnosed with AD.
Wolf and colleagues followed 1,092 people in a "dementia-free" group of the
Framingham cohort. Participants in this group, whose average age was 76,
were enrolled in the study between 1976 and 1978. Plasma homocysteine levels
were measured between 1979 and 1982 and between 1986 and 1990. Researchers
also considered age, sex, vascular risk factors other than homocysteine, and
plasma levels of folate and vitamins B6 and B12 of the participants.
Information from the participants was also available on the late-onset AD
genetic risk factor APOE-e4.
From the 1986-1990 examinations through December 2000, some 111 people
developed dementia, including 83 diagnosed specifically with AD. Elevated
homocysteine levels (defined as greater than 14 mmol/liter) doubled the
chance that a participant would develop AD and each 5 mmol/liter elevation
increased the risk of AD by 40 percent. The analysis showed further that
people with consistently high levels of homocysteine throughout the period
of the study were at highest risk for dementia and AD. The researchers also
examined whether the earlier levels of homocysteine, measured between 1979
and 1982, had any relationship to the development of dementia or AD later
on; this analysis, too, linked elevated levels at least 8 years prior to a
later diagnosis of dementia and AD. The association between homocysteine and
AD was found to be strong and independent of other factors, such as age,
gender, APOE genotype, and other known or suspected risk factors for
dementia and AD.
There was no direct association in this study between the serum levels of
folate and vitamins B6 and B12 and the development of dementia among the
participants. As the relationship between these B vitamin levels,
homocysteine, AD, and cardiovascular disease continues to be studied,
scientists speculate that consuming adequate amounts of B vitamins by diet
or supplementation might help reduce levels of homocysteine in some
individuals. Findings from the NHLBI-supported DASH (Dietary Approaches to
Stop Hypertension) study suggest that a diet rich in green leafy vegetables,
low-fat dairy products, citrus fruits and juices, whole wheat bread, and dry
beans can significantly lower levels of homocysteine. The Food and Drug
Administration (FDA) now requires the addition of folic acid to enriched
breads, cereals, flours, corn meals, pastas, rice, and other grain products.
"Although there is no evidence that actually reducing homocysteine levels
will prevent AD or cardiovascular disease, a healthy diet low in fat and
rich in nutrients is always a good idea," says BU's Wolf.
The NIA leads the Federal effort to support and conduct basic, clinical, and
social and behavioral studies on aging and AD. It supports the Alzheimer's
Disease Education and Referral (ADEAR) Center, which provides information on
AD research, including clinical trials, to the public, health professionals,
and the media. ADEAR can be contacted toll free at 1-800-438-4380 weekdays
or by visiting the website www.alzheimers.org. Press releases, fact sheets,
and other materials about aging and aging research can be viewed at the
NIA's general information website, www.nia.nih.gov.
The NHLBI is the nation's leading supporter of biomedical research on
diseases of the heart, blood vessels, and lung; sleep disorders; and on the
management of blood resources. The Institute's Framingham Heart Study began
in 1948 as the first long-term population-wide epidemiological study and has
led to such medical breakthroughs as identifying the risk factors for heart
disease, including high blood cholesterol and high blood pressure.
Information about Framingham is available online at www.nhlbi.nih.gov/about/framingham.
NHLBI press releases, fact sheets, and other materials are available on the
NHLBI website at www.nhlbi.nih.gov.
Source: National Institute of Health