Journal
ANNALS OF NEUROLOGY
Volume 69, Issue 6, Pages 1032-1042Publisher
WILEY
DOI: 10.1002/ana.22333
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Funding
- National Institutes of Health (NIH) (National Institute on Aging [NIA] [R01-AG027435-S1, P50-AG00513421, P01-AG036694, R01-AG021910, 1K23AG033634]
- Massachusetts Alzheimer's Disease Research Center (ADRC)
- Howard Hughes Medical Institute (HHMI)
- Alzheimer Association [IIRG-06-32444, IIRG-08-90934]
- Charles H. Farnsworth Trust, Boston, MA
- The Rosalinde and Arthur Gilbert Foundation
- NIH
- Elan Pharmaceuticals
- Wyeth
- Bristol-Myers Squibb
- Janssen Immunotherapy
- Pfizer Inc.
- Bayer
- Eisai Inc.
- Myriad Genetics, Inc.
- GlaxoSmithKline
- Neurochem-Alzhemed
- Cephalon, Inc.
- Forest Laboratories Inc.
- Alzheimer's Disease Neuroimaging Initiative
- Dominantly Inherited Alzheimer's Network [NIA 1U01AG032438-01]
- Aging Brain: DTI, Subcortical Ischemia and Behavior [NIA 1 R03 AG023916-01A1]
- The Norman and Rosalie Fain Family Foundation
- Champlin Foundation
- John and Happy White Family Foundation
- NIH/National Institute on Aging
- The Alzheimer Association
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Objective: Both amyloid-beta (A beta) deposition and brain atrophy are associated with Alzheimer's disease (AD) and the disease process likely begins many years before symptoms appear. We sought to determine whether clinically normal (CN) older individuals with A beta deposition revealed by positron emission tomography (PET) imaging using Pittsburgh Compound B (PiB) also have evidence of both cortical thickness and hippocampal volume reductions in a pattern similar to that seen in AD. Methods: A total of 119 older individuals (87 CN subjects and 32 patients with mild AD) underwent PiB PET and high-resolution structural magnetic resonance imaging (MRI). Regression models were used to relate PiB retention to cortical thickness and hippocampal volume. Results: We found that PiB retention in CN subjects was (1) age-related and (2) associated with cortical thickness reductions, particularly in parietal and posterior cingulate regions extending into the precuneus, in a pattern similar to that observed in mild AD. Hippocampal volume reduction was variably related to Ab deposition. Interpretation: We conclude that Ab deposition is associated with a pattern of cortical thickness reduction consistent with AD prior to the development of cognitive impairment. ANN NEUROL 2011;69:1032-1042
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