PROJECT SUMMARY/ABSTRACT Cognitive decline associated with cancer and its therapies, or cancer-related cognitive impairment (CRCI), is a dreaded outcome among older adults with cancer who care about how well they can live after surviving serious illness. In older adults, cognitive decline can have wide-ranging impact on quality of life, functional decline, and loss of independence. However, oncologists have little information to guide counseling on the cognitive risks of cancer and its associated therapies. The existing literature on CRCI, mostly in solid tumors such as breast cancer, report conflicting results and have several limitations, such as difficulty accounting for the multiple factors that influence cognition and lack of information about long-term pre- and post-cancer cognitive trajectories. CRCI is particularly relevant to patients with hematologic malignancies since most have the potential for cure or long-term disease control. However, our understanding of CRCI in hematologic malignancies is limited, which impedes our ability to counsel patients on what to expect cognitively or to identify patients at high-risk of cognitive decline. The objectives of this study are to evaluate the long-term cognitive trajectories of older adults aged >65 years with hematologic malignancies and identify predictors of cognitive decline by leveraging data from the Health and Retirement Study (HRS), which is a longitudinal cohort of nationally representative older adults. We will examine changes in the cognitive trajectories of older adults with hematologic malignancies from years before treatment to years after and compare them to changes in cognitive trajectories in matched non-cancer controls (Aim 1 primary analysis). Because hematologic malignancies and treatments are heterogeneous, we will also characterize the cognitive trajectories of older adults with hematologic malignancies based on clinically relevant disease types, and we will also describe the different types of cognitive trajectories that may exist (Aim 1 secondary analysis). Lastly, we will seek to identify predictors of clinically meaningful cognitive decline with a focus on disease/treatment-related variables and modifiable risk factors that will inform treatment discussions and the design of interventions (Aim 2). This study will help fill the critical knowledge gap about the cognitive trajectories of older hematologic malignancy survivors by comparing the change in cognition to what happens with normal aging, characterizing potentially different trajectories based on clinically relevant disease types, and describing different types of trajectories that patients may experience. In addition, the identification of predictors of clinically meaningful cognitive decline will provide important prognostic information to inform treatment discussions and lay the groundwork for the development of future screening tools to identify high-risk subgroups and interventions to mitigate the risk of CRCI.

PROJECT NARRATIVE The National Institute on Aging has called for increased research to advance our progress against Alzheimer’s disease and related dementias, yet in oncology research there are still major knowledge gaps in cancer-related cognitive impairment, particularly in hematologic malignancies. We propose a study to better characterize the long-term cognitive trajectories of older adults with hematologic malignancies and to identify predictors of clinically meaningful cognitive decline. The results of this study will improve our ability to counsel patients with hematologic malignancies on what to expect cognitively and to identify those at high-risk of cognitive decline for targeted screenings or interventions.