Multiple drug use or polypharmacydue to medications from different classes that share similar pharmacol- ogical side effects is of concern in older adults. CNS polypharmacy is a commonand important exampleof this phenomenon. CNS polypharmacy may contribute to the development of geriatric syndromes.Geriatric syndromes such as cognitive impairment, urinary incontinence and mobility/instability problems are also common, morbid and costlyfor older adults. With the trend towards increased use of medications, information is needed regarding the impact of CNS polypharmacy on geriatric syndromesin older adults. The long term objectiveis to enhance the health of the elderly by determining the dynamic effects over time of exposure and changes in CNS polypharmacy on geriatric syndromes, so that interventions can be designed, health outcomes improved and health care costs reduced. Using a longitudinal design, the immediate objective is to determine the impact over time of CNS polypharmacyon geriatric syndromes.CNS poly- pharmacy will be defined as: 1)the use of 2 or more medications from any of six medication classes (i.e., benzodiazepines, other anxiolytics/ hypnotics, opioid analgesics, antidepressants, antipsychotics and anti- epileptics) and 2) combined standardized daily dosage of these multiple CNS medications. We will determine mobility/instability performance (i.e., EPESE lower extremity battery, 400 meter walk, balance, self-reported falls), cognitive function (i.e., 3MS), and self-reported urinary incontinence. The specific hypotheses to be tested are that, compared with non affected elders, elderly participants with prevalent, incident and increasing CNS polypharmacy will have greater mobility/instability decline, increased cognitive decline, and increased likelihood of urinary incontinence after controlling for important covariates (e.g. comorbidities).This study capitalizes on data from the NIA-funded longitudinal Health ABC study. The current proposal is likely to be highly cost-effective and can be expected to yield results that are valid and generalizable to older adults.