Normal and Pathological Aging: From Animals to Humans

Abstract

While aging is associated with modest declines in certain aspects of cognitive function (memory, executive function, processing speed), many cognitive domains can remain relatively stable until late in life. In contrast to the mild decline observed in normal aging, pathological aging such as Alzheimer’s disease (AD) affects global cognitive function – impairing memory, language, thinking, and reasoning, and interferes substantially with daily living capacity. Changes in the structural integrity of the brain underlie the cognitive declines that occur in both aging and AD, however different brain structures are affected. In healthy aging, mild functional changes are predominantly detected in the prefrontal cortex and basal ganglia, while in AD, pathology initially accumulates and disrupts function in the medial temporal lobe (disrupting memory), progresses to cortical structures, and eventually globally impacts the brain. Cognitive decline with normal and pathological aging is mediated by a complex interaction of multiple factors that include genetic and nongenetic risk factors that determine the age of onset as well as the rate of decline. Importantly, the progression and decline can be prevented or slowed by certain lifestyle factors (exercise participation, stress management) and pharmaceutical interventions (statins, hormone replacement therapy for postmenopausal women). While most individuals will experience some degree of cognitive decline with aging, conversion to MCI or AD is not an inevitable consequence of aging. It is likely that additional strategies to promote healthy brain aging will be uncovered in the next years that will further contribute to successful brain aging and will help to maintain a high quality of living through the last decades of life.