Brain aging research relies mostly on cross-sectional studies, which infer true changes from age differences. We present longitudinal measures of five-year change in the regional brain volumes in healthy adults. Average and individual differences in volume changes and the effects of age, sex and hypertension were assessed with latent difference score modeling. The caudate, the cerebellum, the hippocampus and the association cortices shrunk substantially. There was minimal change in the entorhinal and none in the primary visual cortex. Longitudinal measures of shrinkage exceeded cross-sectional estimates. All regions except the inferior parietal lobule showed individual differences in change. Shrinkage of the cerebellum decreased from young to middle adulthood, and increased from middle adulthood to old age. Shrinkage of the hippocampus, the entorhinal cortices, the inferior temporal cortex and the prefrontal white matter increased with age. Moreover, shrinkage in the hippocampus and the cerebellum accelerated with age. In the hippocampus, both linear and quadratic trends in incremental age-related shrinkage were limited to the hypertensive participants. Individual differences in shrinkage correlated across some regions, suggesting common causes. No sex differences in age trends except for the caudate were observed. We found no evidence of neuroprotective effects of larger brain size or educational attainment.

Cognitive decline is commonly observed in advanced aging even in the absence of disease. Here we explore the possibility that normal aging is accompanied by disruptive alterations in the coordination of large-scale brain systems that support high-level cognition. In 93 adults aged 18 to 93, we demonstrate that aging is characterized by marked reductions in normally present functional correlations within two higher-order brain systems. Anterior to posterior components within the default network were most severely disrupted with age. Furthermore, correlation reductions were severe in older adults free from Alzheimer's disease (AD) pathology as determined by amyloid imaging, suggesting that functional disruptions were not the result of AD. Instead, reduced correlations were associated with disruptions in white matter integrity and poor cognitive performance across a range of domains. These results suggest that cognitive decline in normal aging arises from functional disruption in the coordination of large-scale brain systems that support cognition.

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In a prospective cross-sectional study, we used computerized volumetry of magnetic resonance images to examine the patterns of brain aging in 148 healthy volunteers. The most substantial age-related decline was found in the volume of the prefrontal gray matter. Smaller age-related differences were observed in the volume of the fusiform, inferior temporal and superior parietal cortices. The effects of age on the hippocampal formation, the postcentral gyrus, prefrontal white matter and superior parietal white matter were even weaker. No significant age-related differences were observed in the parahippocampal and anterior cingulate gyri, inferior parietal lobule, pericalcarine gray matter, the precentral gray and white matter, postcentral white matter and inferior parietal white matter. The volume of the total brain volume and the hippocampal formation was larger in men than in women even after adjustment for height. Inferior temporal cortex showed steeper aging trend in men. Small but consistent rightward asymmetry was found in the whole cerebral hemispheres, superior parietal, fusiform and orbito-frontal cortices, postcentral and prefrontal white matter. The left side was larger than the right in the dorsolateral prefrontal, parahippocampal, inferior parietal and pericalcarine cortices, and in the parietal white matter. However, there were no significant differences in age trends between the hemispheres.

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