PROJECT Chronic individuals dementias kidney CKD. risk SUMMARY kidney disease (CKD) is a highly morbid disease t hat disproportionately affects older and is associated with a significantly increased risk of Alzheimer's and related (ADRD). However, many older adults have “benign” kidney senescence, in which function declines due to natural aging, and do not experience the extrarenal sequelae of Research is needed to target therapies towards older patients with CKD who are at high for ADRD. Renin-angiotensin treatment. effects to dysregulation pathologic mitigation enormous The kidney system (RAS) inhibition with ARBs or ACEIs is the backbone of CKD Preliminary evidence suggests that ARBs may have greater beneficial cognitive than ACEIs in the general population. Older individuals with pathologic CKD, as opposed kidney senescence, may particularly benefit cognitively from ARBs vs. ACEIs due amplified of the RAS in CKD. It is still unknown, however, how to distinguish patients with CKD versus benign senescence. D etermining if ARBs vs. ACEIs have greater of the long-term ADRD risk in older patients with pathologic CKD could have an public health impact in this vulnerable population. proposed study aims to evaluate the benefit of ARBs vs ACEIs in older adults with reduced function. Utilizing theelectronic health record data from the Veterans Health Administration linked with Medicare, we will estimate the effects of ARB- vs. ACEI-based medication regimens on the incidence of dementia using advanced causal inference methods. Subsequently, we will perform a cluster analysis to identify phenotypic subgroups of older adults with CKD based on clinical, demographic and laboratory data and will test whether any of these groups show differential cognitive outcomes with ARBs vs ACEIs. In Diversity Supplement will machine will treatment conjunction with her prepared areer development plan, the proposed project for the provide Dr. Shulman with training in dvanced causal inference and learning techniques and will generate four first-author manuscripts These experiences inform her planned submission of a career development award focused on advancing the and prevention of adverse cognitive outcomes in older patients with CKD. c NIA a .