A Systems Approach to the Aging Brain: Neuroanatomic Changes, Their Modifiers, and Cognitive Correlates

Success in diagnosing and treating age-related brain disease depends on understanding normative and optimal aging of the brain. Neuroimaging studies of healthy adults reveal differential brain shrinkage. Prefrontal cortices evidence the largest age-related differences, whereas tertiary association cortices, the neostriatum, and the cerebellum show the greatest rate of shrinkage. Reduced regional brain volumes and steeper longitudinal declines are usually associated with lower cognitive performance. Trajectories of differential brain aging are modified by multiple negative and positive factors. Vascular risk factors affect the regions deemed most vulnerable to aging. However, the positive modifying influence of aerobic fitness is clearest in the same age-sensitive areas. Genetic variation may have a significant impact on age-related changes in brain and cognition. In addition to (and in conjunction with) improved aerobic fitness, antihypertensive treatment and hormone replacement therapy may alleviate negative effects of aging on the brain structure.