|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.
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please visit either website.
The National Institutes of Health (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 cures for both common and rare diseases.
For more information about NIH and its programs, visit www.nih.gov.
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.