This proposal seeks support to establish a new NIAAA Alcohol Research Center (ARC) at The University of Michigan to study the effects of alcohol in elderly people. The Center's primary theme will be to determine how alcohol interacts with the aging process central nervous system (CNS) abnormalities of memory, cognition, sleep, mood, neuroendocrine regulation, and immune functions and to develop strategies for earlier diagnosis and treatment so as to prevent development of disabling CNS changes. Addiction to alcohol is particularly devastating to the central nervous system. The drug impairs learning and memory (e.g., short- term learning and memory impairments), interferes with CNS-mediated immune functions (e.g., increased incidences of cancer, degenerative disease and infections), disrupts sleep physiology (e.g., sleep apnea), is associated with mood disorders (especially depression), disinhibits hypothalamic regulation of the pituitary- adrenal neuroendocrine axis (e.g., alcoholic """"""""pseudo-Cushing's syndrome) and alters receptor binding in the brain (possibly playing a role in tolerance, withdrawal seizures, and delirium tremens). At the same time, normal aging significantly alters each of these important CNS functions. Despite their clinical importance, we have little understanding about how aging and alcohol interact to produce these CNS syndromes, primarily because evaluation techniques have been lacking. During the past decade, effective, relatively non-invasive strategies have been developed that enable assessment of brain function in vivo. These include positron emission tomography (PET), magnetic resonance imaging (MRI), sleep EEG analysis, CNS receptor-binding assays, neuroendocrine challenges, and measures of immune competence. This ARC will apply each of these neuroscience strategies to study CNS abnormalities in aged alcoholic persons, emphasizing the testing of specific hypotheses.
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