Abstract

ObjectiveBoth amyloid-β (Aβ) 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 Aβ 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.MethodsA 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.ResultsWe 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 Aβ deposition.InterpretationWe conclude that Aβ deposition is associated with a pattern of cortical thickness reduction consistent with AD prior to the development of cognitive impairment. ANN NEUROL 2010;

Highlights

  • ANNALS of Neurology addition, we evaluated 9 other region of interest (ROI) that are vulnerable to Ab deposition to determine whether Ab-associated volume/thickness changes differed when the proxy measure of Pittsburgh Compound B (PiB) retention was from these alternative ROIs: rostral anterior cingulate, medial orbitofrontal, rostral middle frontal, caudal anterior cingulate, precuneus, superior frontal, pars opercularis, caudal middle frontal, inferior parietal, lateral orbitofrontal, and global

  • Subject Characteristics The Alzheimer’s disease (AD) and clinically normal (CN) groups differed in Mini-Mental State Examination (MMSE) scores and posterior cingulate/precuneus (PCC) PiB retention, but not in age, gender, or education (Table 1)

  • The major finding of this study is that significant Abassociated cortical thinning occurs among CN older individuals in a pattern consistent with early AD

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Summary

Objective

Both amyloid-b (Ab) 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 Ab deposition revealed by positron emission tomography (PET) imaging using Pittsburgh Compound B (PiB) have evidence of both cortical thickness and hippocampal volume reductions in a pattern similar to that seen in AD. We hypothesized that Ab deposition would be associated with local cortical thickness reductions in regions associated with the default network[37] at early stages of the pathophysiological process, prior to cognitive impairment

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