A pharmacologic challenge strategy in Alzheimer patients using cholinergic and non-cholinergic agents has been the focus of this unit for a number of years. We have previously documented that Alzheimer patients are behaviorally and cognitively more sensitive to acute anticholinergic blockade with intravenous scopolamine, suggesting increased functional sensitivity compared to age-matched controls. This year, we have shown that this increased sensitivity is not seen in geriatric depressed patients, another population frequently presenting with cognitive deficits but without documented central cholinergic pathology. This functional sensitivity to anticholinergic agents in dementia patients has potential therapeutic implications, and we are now exploring the sensitivity of this population to a series of cholinergic agonists, including arecoline and nicotine. Another major thrust of our unit has been the therapeutic usefulness of the selective monoamine oxidase inhibitor (MAOI), L-deprenyl, in dementia patients. Work from this last year has demonstrated that deprenyl has beneficial cognitive and behavioral effects in the Alzheimer population without serious side effects. In addition, study of the biochemical changes which accompany the use of this drug has been helpful in characterizing some of the possible mechanisms of action. While the therapeutic benefit was relatively small compared to the overall devastation of the illness, the positive effects were encouraging, and we are currently in the process of studying the longer-term effects of this drug in demented patients.