Amyloid-β associated cortical thinning in clinically normal elderly
Annals of Neurology
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) also have evidence of both cortical thickness and hippocampal volume reductions in a pattern similar to that seen in AD. Methods: A total of
... 19 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. T he possibility of disease-modifying therapies for Alzheimer's disease (AD) has motivated the development of biomarkers that reflect underlying pathologic processes. The sequence of pathologic events in AD likely begins many years, perhaps decades, prior to the development of symptoms. 1,2 Amyloid-b (Ab) deposition appears early in the disease, prior to symptoms, and then plateaus as clinical dementia emerges. 3-6 In contrast, neurodegeneration, including loss of synapses, neurons, and arborization, results in brain atrophy that worsens in parallel with cognitive decline. 2,6,7 The principal early sites of Ab deposition are neocortical, typically in the parietal and frontal regions, 4, 8, 9 whereas the sites of early atrophy include the medial temporal regions. 2,6,10,11 Here we relate these 2 phenomena in vivo in clinically normal (CN) older individuals and in clinically established AD patients, in order to determine the correspondence between levels of Ab deposition and of atrophy. It is now possible to observe the relation between Ab deposition and atrophy in vivo with positron emission tomography (PET) imaging using Pittsburgh Compound B (PiB) 9 and high-resolution volumetric magnetic resonance imaging (MRI) data. 2,6 PiB studies have confirmed what was predicted by earlier postmortem studies, 13-15 that a View this article online at wileyonlinelibrary.com.