A— Age-Related Shifts in Neural Circuit Characteristics and Their Impact on Age-Related Cognitive Impairments

John H. Morrison

INTRODUCTION

Increasing chronological age carries with it a heightened risk for diseases such as Alzheimer's disease, as well as functional decline associated with senescence in the absence of any specific neurologic disease, such as age-related memory impairment. Alzheimer's disease leads to a catastrophic decline in cognitive abilities and memory performance in the affected individual. Age-related memory impairment in the context of senescence is far less catastrophic than Alzheimer's disease with respect to the quality of life, but it has a surprisingly high incidence and thus also represents a significant health problem associated with aging. With the increased life expectancy that has already occurred over the last century, let alone the projected further increase, it has become clear that one of the most important goals for neuroscientists over the next several decades will be to develop means of maintaining a high level of cognitive and memory performance in the aged population. The focus of this paper is to outline and to illustrate a circuit-based approach aimed at both revealing the neurobiological basis of age-related memory impairment and identifying targets for intervention.

A Multitiered Neuroanatomic Approach to Aging

The Link between Neurochemistry and Neuroanatomy

Traditionally, a given cell class or circuit has been defined and/or categorized on the basis of its physiological and anatomic characteristics, i.e., the



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