Neurochemical and pharmacological studies establish a rationale for clinical trials of drugs that increase central cholinergic activity in patients with a diagnosis of Alzheimer's disease, and in normal elderly people with an age-related loss in memory functioning. The major goal of the project is to test potential cholinomimetic compounds in patients with Alzheimer's disease, normal elderly people with an age-related memory loss and in normal young subjects, to determine the ability of these drugs to enhance memory functioning. Various cholinergic agents with different mechanisms of action will be tested and compared in the same patients to determine their relative abilities to imprve the ability of patients and subjects to learn new information. These drugs include, precursors to acetylcholine, acetylcholinesterase inhibitors and muscarinic receptor agonists. In all instances broad dose ranging studies are a prerequisite to subsequent studies. As these sudies are being conducted, an attempt will be made to determine if the cholinergic deficit that exists in Alzheimer's disease, and exists to a lesser extent in normal elderly people, can be detected in vivo by measurements of cerebrospinal fluid or neuroendocrine parameters.
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