PROJECT SUMMARY/ABSTRACT. Polypharmacy is a highly prevalent problem in older adults, particularly in those with Alzheimer’s Disease (AD) and AD-Related Dementias (AD/ADRD) and those residing in the nursing home (NH). Many older adults continue to receive medications originally prescribed for disease prevention until the end of life, despite a lack of sufficient evidence to justify their continued use in advanced age. The use of bisphosphonates for fracture prevention is one example. Although bisphosphonates are effective in reducing fractures in healthier, community-dwelling individuals, there is insufficient evidence of continued benefits that is generalizable for NH residents with AD/ADRD. There is also substantial clinical heterogeneity in this population with regards to fracture risk, mobility, and life expectancy, creating further uncertainty as to whether all NH residents with AD/ADRD benefit from bisphosphonate use. Deprescribing is a patient-centered approach to reduce or stop medications that are no longer appropriate considering goals of care, time until benefit, and life expectancy. Considering the lack of strong generalizable evidence and potential for side effects, bisphosphonates may be targeted for deprescribing in NH residents with AD/ADRD. Deprescribing may also be justifiable considering the extended period of benefit of bisphosphonates, which may last for up to 2 years after discontinuation exceeding the life expectancy of many residents with AD/ADRD. However, no studies to date have evaluated the appropriateness of deprescribing bisphosphonates as a means to reduce the burden of polypharmacy and adverse effects in this population. Large observational studies of secondary data are uniquely positioned to evaluate the benefits and harms of medication use and deprescribing in older NH residents with AD/ADRD, given the barriers to conducting randomized studies in this population. This study will evaluate determinants, clinical outcomes, and cost-effectiveness of deprescribing bisphosphonates in NH residents with AD/ADRD. In Aim 1, we will conduct a qualitative study using semi-structured interviews to identify determinants of deprescribing bisphosphonates from the perspectives of family/informal caregivers and prescribers of NH residents with AD/ADRD. In Aim 2, we will conduct an observational study of Medicare administrative data to evaluate clinical outcomes (fractures and adverse effects) associated with deprescribing bisphosphonates in a sample of older NH residents with AD/ADRD. In Aim 3, we will evaluate the cost-effectiveness of deprescribing bisphosphonates in NH residents with AD/ADRD, considering medication costs and utilization for fractures and adverse effects. This study will address a critical gap in knowledge and inform future recommendations for optimizing bisphosphonate use to prevent fractures in this vulnerable and medically complex population. This award will also provide the principal investigator with protect...