Covarying alterations in Aβ deposition, glucose metabolism, and gray matter volume in cognitively normal elderly

β-Amyloid (Aβ), a feature of Alzheimer's disease (AD) pathology, may precede reduced glucose metabolism and gray matter (GM) volume and cognitive decline in patients with AD. Accumulation of Aβ, however, has been also reported in cognitively intact older people, although it remains unresolved whether and how Aβ deposition, glucose metabolism, and GM volume relate to one another in cognitively normal elderly. Fifty-two cognitively normal older adults underwent Pittsburgh Compound B–positron emission tomography (PIB-PET), [18F]fluorodeoxyglucose-PET, and structural magnetic resonance imaging to measure whole-brain amyloid deposition, glucose metabolism, and GM volume, respectively. Covariance patterns of these measures in association with global amyloid burden measured by PIB index were extracted using principal component analysis–based multivariate methods. Higher global amyloid burden was associated with relative increases of amyloid deposition and glucose metabolism and relative decreases of GM volume in brain regions collectively known as the default mode network including the posterior cingulate/precuneus, lateral parietal cortices, and medial frontal cortex. Relative increases of amyloid deposition and glucose metabolism were also noted in the lateral prefrontal cortices, and relative decreases of GM volume were pronounced in hippocampus. The degree of expression of the topographical patterns of the PIB data was further associated with visual memory performance when controlling for age, sex, and education. The present findings suggest that cognitively normal older adults with greater amyloid deposition are relatively hypermetabolic in frontal and parietal brain regions while undergoing GM volume loss in overlapping brain regions. Hum Brain Mapp 35:297–308, 2014. © 2012 Wiley Periodicals, Inc.