Risk for Alzheimer's Disease
Amyloid Deposits in Cognitively Normal People May Predict Risk
for Alzheimer's Disease
For people free of dementia, abnormal deposits of a protein associated with
Alzheimer's disease are associated with increased risk of developing the
symptoms of the progressive brain disorder, according to two studies from
researchers at Washington University in St. Louis. The studies, primarily funded
by the National Institute on Aging (NIA), part of the National Institutes of
Health, linked higher amounts of the protein deposits in dementia-free people
with greater risk for developing the disease, and with loss of brain volume and
subtle declines in cognitive abilities.
The two studies are reported in the Dec. 14, 2009, online issue of Archives
of Neurology. The scientists used brain scans and other tests to explore the
relationship between levels of beta-amyloid, a sticky protein that forms the
hallmark plaques of Alzheimer's disease, and dementia risk in cognitively normal
people. John C. Morris, M.D., who directs the NIA-supported Alzheimer's Disease
Research Center at Washington University in St. Louis, and his team conducted
the research. Martha Storandt, Ph.D., also of Washington University in St.
Louis, directed one of the studies.
“Previous studies of brain pathology, cognitive testing, and brain imaging
have for some time suggested that Alzheimer's pathology causes changes to the
brain many years before memory loss, confusion, and other symptoms of the
disease are apparent. But it remains difficult to accurately predict whether a
cognitively normal person will—or will not—develop the disease,” said NIA
Director Richard J. Hodes, M.D. “These new studies suggest that beta-amyloid
measured in the brains of cognitively normal individuals may be a preclinical
sign of disease.”
Morris' team used a variety of measures to look for changes in the brain in
the two studies, including positron emission tomography (PET) imaging using a
radioactive form of Pittsburgh Compound B (PiB), an agent specially developed to
detect levels of beta-amyloid protein in the living brain; magnetic resonance
imaging (MRI) to measure brain volume; and standardized clinical tests of memory
and thinking abilities to determine cognitive health. Previously, the link
between beta-amyloid load and Alzheimer's disease could only be confirmed at
autopsy.
The studies indicated that beta-amyloid might be present in the brain even in
symptom-free people:
- Between 2004 and 2008, researchers used PiB scans to track 159 volunteers
ages 51 to 88, who started the study with no signs of cognitive impairment, to
see if there was a correlation between beta-amyloid levels and cognitive health.
Over time, 23 participants developed mild impairments, and nine were eventually
diagnosed with clinical Alzheimer's disease. Compared with participants who
remained cognitively normal, the nine who were eventually diagnosed clinically
with Alzheimer's disease had high levels of PiB binding in the brain and
experienced cognitive decline as well as volume loss in the parahippocampal
gyrus, a part of the brain that controls memory. However, not every person who
had beta-amyloid deposition in the brain developed cognitive impairment.
Beta-amyloid deposition may be a risk factor for developing Alzheimer's disease
but its presence does not constitute a diagnostic finding.
- In 135 cognitively normal older adults aged 65 to 88, the level of
beta-amyloid as measured by PiB binding correlated with atrophy, or shrinkage,
in many parts of the brain and to declines on memory and thinking tests over
many years.
“More study is needed in larger groups for longer periods, but these studies
confirm the value of detecting and measuring amyloid load in the brains of
living people as soon as possible,” said Morris. “These imaging tools are an
important part of ongoing effort to create a profile of Alzheimer's in its
earliest stages, even before symptoms appear, by linking imaging results with
other biomarkers and clinical evaluations.”
Additional funding came from the Charles and Joanne Knight Alzheimer's
Research Initiative of the Washington University Alzheimer's Disease Research
Center, St. Louis, and from an anonymous foundation.
The NIA leads the federal government effort conducting and supporting
research on the biomedical, social and behavioral issues of older people. For
more information on aging-related research and the NIA, go to www.nia.nih.gov.
The NIA provides information on age-related cognitive change and
neurodegenerative disease specifically at its Alzheimer's Disease Education and
Referral (ADEAR) Center site at www.nia.nih.gov/Alzheimers.
To sign up for e-mail alerts about new findings or publications, please visit
either website.
The NIH—The Nation's Medical Research Agency—includes 27 institutes and
centers and is a component of the U.S. Department of Health and Human Services.
It is the primary federal agency for conducting and supporting basic, clinical
and translational medical research, and it investigates the causes, treatments,
and curesfor both common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.
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Morris JC, Roe CM, Grant EA, Head D, Storandt M, Goate AM, Fagan AM, Holtzman
DM, Mintun MA. Pittsburgh Compound B imaging and prediction of progression from
cognitive normality to symptomatic Alzheimer's disease. Archives of Neurology,
Dec. 14, 2009.
Storandt M, Mintun MA, Head D, Morris JC. Cognitive decline and brain volume
loss are signatures of cerebral amyloid beta deposition identified with PiB.
Archives of Neurology, Dec. 14, 2009.