Differential aging of the brain: Patterns, cognitive correlates and modifiers

Deciphering the secret of successful aging depends on understanding the patterns and biological underpinnings of cognitive and behavioral changes throughout adulthood. That task is inseparable from comprehending the workings of the brain, the physical substrate of behavior. In this review, we summarize the extant literature on age-related differences and changes in brain structure, including postmortem and noninvasive magnetic resonance imaging (MRI) studies. Among the latter, we survey the evidence from volumetry, diffusion-tensor imaging, and evaluations of white matter hyperintensities (WMH). Further, we review the attempts to elucidate the mechanisms of age-related structural changes by measuring metabolic markers of aging through magnetic resonance spectroscopy (MRS). We discuss the putative links between the pattern of brain aging and the pattern of cognitive decline and stability. We then present examples of activities and conditions (hypertension, hormone deficiency, aerobic fitness) that may influence the course of normal aging in a positive or negative fashion. Lastly, we speculate on several proposed mechanisms of differential brain aging, including neurotransmitter systems, stress and corticosteroids, microvascular changes, calcium homeostasis, and demyelination.