SLEEP & MENTAL FUNCTION IN THE AGED--ANABOLIC INFLUENCE

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Older adults complain of memory loss, sleep disorders, frailty, and loss of lean body mass; age-related decreases in cognitive ability, sleep quantity and quality, lean body mass (LBM), and anabolic hormones such as growth hormone (GH) are well-documented. Preliminary evidence from our database suggests that these changes may be interrelated. We observed that anabolic status (as indexed by plasma insulin-like growth factor, or IGF), correlates significantly and positively with better sleep quality (increased slow wave sleep, decreased wakefulness, and decreased fragmentation of sleep) and with cognition, particularly memory and attention in healthy seniors. These preliminary results lead us to hypothesize that measures of peripheral anabolic status (e.g., sex hormones, LBM, and particularly GH and IGF) may index central nervous system (CNS) status in older adults. While GH and IGF are well-known to index somatic status, their relationship to CNS function has been largely ignored. There are no such studies in the elderly, who are more likely to suffer from impaired sleep and cognition and have lower GH and IGF levels than the young. The proposed study will expand our existing data base to clarify the relationships among anabolic hormone status, sleep quality and cognitive function in subsets of controls drawn from our already-existing samples of healthy older control adults (n=280). Our hypotheses will be tested in approximately 140 control subjects. To evaluate anabolic status, blood will be sampled via slow withdrawal pump across 24-hours. Pooled plasma will be assayed for integrated 24-hour levels of GH, IGF, cortisol, free testosterone (in men), and thyroid hormones (T3,T4). Binding proteins for GH and testosterone will also be measured. Twenty-four hour urinary estrone and estradiol will be measured in women. Lean body mass will be determined via bio-impedance. Sleep variables will include stages of sleep and wakefulness, sleep fragmentation (stage changes) and consolidated (sleep period time), as well as total EEG delta activity (computer derived). Relationships between anabolic status and sleep will be identified using multiple regression techniques. Cognitive tests will include Rivermead Behavioral Memory, Dementia Rating Scale, a paired associates learning task, a working memory task (Verbal Sets), a selective attention task (Brief Test of Attention), and a verbal fluency test. Relationships between anabolic status and cognition will also be identified using multiple regression techniques. These studies will identify levels of anabolic hormones that are associated with high sleep quality and good cognitive function in senior adults. They will also foster the design of appropriate GH and IGF intervention studies targeted at improving cognition/sleep in seniors. Our larger long-term objective is to elucidate the role of GH and IGF and related hormones in the neurobiology of aging.