Proj. 1: HOME-BASED ASSESSMENT OF ELDERLY AT RISK FOR COGNITIVE DECLINE, MCI AND AD This proposal will develop efficient and sensitive home-based methods to capture cognitive decline and dementia in the elderly as outcomes for clinical trials aimed at primary prevention of ADr Participants for primary prevention trials are those most at risk for dementia, including the very elderly who often have physical, social and health restrictions that make it difficult to participate in clinic based assessments and therefore difficult to recruit into studies. This proposal will focus on home-based assessments to maximize participation and reduce the expense and burden of traditional, in-person, assessment. The specific aims are to develop home based assessments of important domains that mark the transition from cognitive health to cognitive impairment and dementia in a broad cohort of elderly individuals. We will validate and compare the efficiency of three methods of assessment by comparing them to traditional inperson evaluations conducted in the clinic, home or other setting. The three methods to be examined are: (a) Mail-in questionnaires plus a validated cognitive assessment via telephone; (b) presentation and data collection via automated telephone technology, and (c) computerized presentation and data collection. The assessments, common to all three administration methods, will cover domains known or likely to be important in early detection of cognitive decline: neuropsychological impairment, functioning in daily life, affective and behavioral symptoms, global change, quality of life and resource use. In a simulated primary prevention trial study design, we will randomly assign 600 non-demented elderly over the age of 75 to one of three evaluation methods (200 per group). Traditional in-person evaluations that use established, standardized, criteria-based diagnostic assessments will serve as the gold standard for comparison with the experimental home-based methods and instruments. We will also simulate a medication adherence protocol that will use a twice a day multivitamin regimen. We will determine if medication compliance (as a real-life measure of functional status), and a more detailed exposition of the subject's perception of key elements of IADL measures have greater predictive value for early cognitive deterioration than existing cognitive measures. Additional measures to detect early cognitive decline will also be examined, including patterns of response. Finally we will determine if frequency of assessment is associated with sensitivity of measurement of meaningful clinical and cognitive change by comparing subgroups assessed at home at 3, 6 or 12 month intervals over a period of 4-years. We will determine if more frequent assessment can capture subtle change in slope which may permit earlier detection of true deterioration.