NEUROLOGICAL FACTORS IN COGNITIVE AGING

In the past century, average life expectancy in the United States increased by approximately 30 years, primarily because of reduced mortality from common conditions in early and midlife. As a result, there has been a substantial increase in the proportion of older people in the population, and this proportion is expected to further increase in the first half of the current century as the post–World War II generation ages. With the aging of the population, common chronic conditions of old age have come to pose an increasing public health burden. In particular, cognition-impairing conditions such as Alzheimer’s disease that are relatively uncommon before age 65 have now become leading causes of morbidity and mortality. Therefore, identifying factors that may prevent or delay age-related cognitive decline is of great public health importance. The central premise of this chapter is that age-related cognitive decline represents the interaction of experiential and genetic risk factors with multiple age-associated neuropathologic processes taking place in brains with differing structural and functional characteristics prior to old age. According to this view, age-related loss of cognition is not a normal developmental process or an inevitable outcome of old age but rather the result of different age-related neuropathologic lesions accumulating at different rates in different brain regions of individuals with differing vulnerabilities to the lesions; that is, risk factors may contribute to loss of cognition either by affecting the accumulation of common neuropathologic lesions or by somehow affecting the ability to maintain function despite accumulating pathology. To the extent that this view is valid, understanding the neurobiologic pathways linking risk factors to age-related loss of cognition is likely to be critical to research on prevention. The remainder of this chapter is divided into three parts. In the first section, I describe four neuropathologic lesions that are common findings on postmortem examinations of the brains of old people and discuss their distribution and relation to cognition in people with and without dementia. In the second section, I consider selected predictors of age-related cognitive decline and propose different neurobiologic bases for the associations. In the final section,