The goal of the present study was to determine the earliest patterns of hypometabolism and atrophy in the development of Alzheimer's disease (AD). Stages of AD were defined by positron emission tomography imaging evidence of cortical amyloid pathology in addition to cognitive criteria. Subjects for the study were selected from the Alzheimer's Disease Neuroimaging Initiative database and divided into 4 groups: cognitively normal (CN) amyloid negative (Aβ-) elderly subjects (n = 36), CN amyloid-positive (Aβ+) (n = 21), early mild cognitive impairment Aβ+ (n = 65), and late mild cognitive impairment Aβ+ (n = 23) subjects. Region of interest-based (primary) and voxel-based (secondary) analyses were used to assess gray matter hypometabolism, quantified by [18F]fluorodeoxyglucose-positron emission tomography, and decrease in gray matter volume and cortical thickness was measured by magnetic resonance imaging. Region of interest- and voxel-based analyses showed significant hypometabolism but not atrophy in CN Aβ+ subjects compared with CN Aβ- subjects. The results suggest that hypometabolism exceeds atrophy in preclinical AD, supporting the notion that amyloid load may affect synaptic activity, leading to synaptic loss and subsequent neuronal loss.
Keywords: Alzheimer's disease; Amyloid; Imaging biomarkers; Mild cognitive impairment.
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