Recent literature suggests that stress may have an interactive effect with normal aging, resulting in elevated cortisol levels, acceleration of hippocampal atrophy, memory decline and/or the development Alzheimer's Disease. Preliminary data from our center indicates that Apolipoprotein E genotype may also impact the relationship between stress, cortisol and cognitive decline. If stress-associated abnormalities in cortisol response impact hippocampal function and cognitive decline with age, this could have significant implications for the use of both pharmacological and non- pharmacological interventions for reducing this response and ultimately reducing cognitive decline and/or progression to dementia. The development of such interventions requires a clearer understanding of the relationships among psychosocial stress, cortisol response, hippocampal volume, Apolipoprotein E genotype and how they may interact to impact variables has limited our ability to ascertain which of these variables may represent the mechanisms of action (mediators) underlying any stress- related decline in cognition in older adults; of which variables may be risk factors (moderators) for stress-related decline in cognition with age. The primary aim of this proposal is to more fully elucidate the complex relationships among stress, cortisol, hippocampal volume, Apolipoprotein E genotype and cognitive decline in community-dwelling, older adults. To achieve our primary aim, we will conduct a longitudinal investigation of 200 community-dwelling older adults, 70 years of age and older. The primary measures in the current study are longitudinal measures of psychosocial stress, cortisol response, and cognitive performance. Each subject will be followed over a three-year period, with all subjects receiving a baseline assessment and three annual follow-up evaluations of cognition. Measures of all subjects receiving a baseline assessment and three annual follow-up evaluation of cognition. Measures of psychosocial stress and cortisol response will be assessed every four months throughout the three-year period. In addition, apolipoprotein E genotype will be established on all subjects at baseline. A subgroup of 50 subjects, randomly selected, will also receive annual assessments of hippocampal volume using structural MRI.
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