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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.
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