One of the most devastating maladies of advancing age in humans is the deterioration of cognitive function that occurs with normal aging and neurodegenerative diseases such as Alzheimer's disease (AD). How aging promotes the pathogenesis of AD and other neurodegenerative diseases in humans remains unclear, but the uniquely long period of senescence in humans compared to other primates may be a predisposing factor. The direct comparison of age-related cognitive decline in humans and two nonhuman primates with distinct life histories and adaptations, the rhesus monkey and the chimpanzee, could yield important clues to the uniquely human predisposition to neurodegenerative diseases and the aging phenotype of the three species. In doing so, we will restrict our investigation to females. First, females outlive males in both humans and chimpanzees and are therefore more likely to be affected by age-related cognitive decline in these species. Second, the extent to which the lifespan expands beyond the reproductive years in females may play a critical role in shaping the patterns of cognitive aging in the three species. The proposed study will examine young and old adults of each species longitudinally for 5 years, including 1) twelve young, 12 middle aged, and 12 old female rhesus monkeys;(2) twelve young, 12 middle aged and 12 old female chimpanzees;(3) Fifty-four volunteer women, equally divided into three age groups: (Young 18-25 years old;middle-aged 40-59 years old;and old 60-80 years old);(4) 18 women with Mild Cognitive Impairment (MCI) and (5) 18 women with AD. In addition, 300 normal women will be recruited to verify that the tests classically used to assess cognitive function in nonhuman primates measure the same abilities in humans. We will evaluate hypotheses concerning the neural and socioemotional concomitants of age-related cognitive decline in the three species.
The specific aims of the Cognitive Aging project are to: 1. Conduct longitudinal studies of cognitive decline in human, chimpanzee, and rhesus monkey females, examining the rates of decline in, and sequential appearance of cognitive deficits in the 3 species. 2. Determine the relationships between age-related cognitive decline and age-related socioemotional and neural changes in the three species. 3. Test the construct validity of tasks used in animal models and in humans. The data will provide new insights into the biology of age-related functional decline in female primates, and into the factors that govern successful versus unsuccessful aging. This information will also facilitate the development of treatments for diseases such as AD.
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