PROJECT SUMMARY Age is a risk factor for Alzheimer’s Dementia (AD) and hematological malignancies. The purpose of this supplement is to understand the prevalence and impact of AD-neuropathology and inflammation on cancer-related cognitive decline (CRCD) in older adults undergoing hematopoietic cell transplantation (HCT). We will examine the interaction between CRCD and AD, in the context of a physical activity intervention study. The parent award (NIA K23; PI Koll), which is currently in the RCT phase, aims to evaluate the feasibility and preliminary efficacy of a 6-month, moderate- intensity physical activity intervention on cognitive function in older adults undergoing HCT. The K23 study includes measures of cognitive domains vulnerable to CRCD, physical function and physical activity. This supplement will add measures of brain volumes (MRI), inflammation, and AD biomarkers in both the immediate intervention and the waitlist control group. Data collection will occur during Year 4-5 of the K23 study. We will test the association between pre-HCT (baseline) AD neuropathology on cognitive function and brain volumes longitudinally (Aim 1). We will examine the effect of physical activity on the change in cognitive function and brain volume longitudinally (Aim 2). We will explore the association between biomarkers of inflammation, cognitive function and brain volume at baseline and 12 months post-HCT (Aim 3). The results of this research will expand our knowledge on the shared mechanisms and interactions between AD and CRCD.