This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Memory loss ranks high among the health issues that concern senior citizens. Most of the elderly affected have memory deficits that are not directly attributable to vascular or degenerative disorders. Hence, there is a great need to conceptualize and test other candidate mechanisms for these impairments. The goal of this proposal is to assess, among non-demented, non-diabetic elderly, the impact of poor peripheral glucose regulation and cortisol dysregulation on hippocampal volume and memory performance. Hippocampal structure will be assessed by means of MRI-derived volumes and its function by declarative memory assessments. It is believed that individuals with poor glucose regulation or cortisol dysregulation will have specific reductions in hippocampal volumes that will be associated with specific impairments in declarative memory performance. There is strong preliminary data pointing to the feasibility of these hypothesized cross-sectional relationships. In addition, the investigators hypothesize that there will be a cumulative effect; individuals with both poor glucose regulation and cortisol dysregulation will be more affected. The investigators also predict that longitudinal declines in glucose regulation or increases in cortisol dysregulation will place elderly individuals at risk for larger losses in hippocampal structure and function. Older women are more likely than men to have alterations in cortisol feedback inhibition, to have increased vulnerability to elevated cortisol levels, and to show stronger age-related hippocampal atrophy. Consequently, the impact of gender will be specifically examined in the hypothesized relationships. Individuals spanning the whole range of cognitive performance in the non-demented range will be studied. The investigators hope to assess 120 volunteers, 60 to 75 years of age and 50% female so as to have over 40 subjects in each gender group at follow-up, assuming a 30% attrition rate at the two year follow-up. The investigators have developed valid and reliable MRI-based hippocampal measurement methods and have a long history of working with the population proposed for study.
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