Ambient Outdoor Heat and Alzheimer's Disease and Related Dementias Risk: A Biopsychosocial Approach to Vulnerability in Older Adults - PROJECT SUMMARY The objective of this K99/R00 proposal is to facilitate Dr. Choi to establish an independent and specialized research program on climate hazards and the risk of Alzheimer’s Disease and Related Dementias (ADRD). The frequency, intensity, and duration of extreme heat events are expected to grow rapidly in the coming decades, affecting over 100 million Americans in 2050. High temperatures may pose significant hazards for cognitive and brain health. Yet, the precise nature and magnitude of extreme heat-induced ADRD risks remain unclear, particularly among a diverse older population. This project aims to fill this gap by providing Dr. Choi with strong content and methodological expertise in the social vulnerability approach to heat and neurobiological underpinnings to determine if high outdoor temperatures increase ADRD risks and to assess how socioeconomic and environmental factors at personal and community levels modify these risks. This project merges longitudinal daily climate records with neighborhood contextual data and the nationally representative and diverse Health and Retirement Study of U.S. adults aged 50, which has collected decades of data on cognitive function, dementia, social factors, and recently, neuropathological biomarkers. In the K99 phase, four training objectives support Dr. Choi’s transition into a leading interdisciplinary investigator who drives substantive questions on how climate hazards affect cognitive health and dementia risk. First, she will develop expertise in heat exposure assessment and the social vulnerability approach. Second, she will acquire knowledge of the biological underpinnings of neurodegeneration and blood-based AD biomarkers. Third, she will cultivate proficiency in advanced longitudinal and mixture analyses to model dynamics across heat and vulnerability factors. Fourth, she will pursue professional development opportunities to establish independence and leadership. This set of training will prepare her to achieve three research aims. Aim 1 determines how outdoor high temperatures contribute to cognitive decline and dementia risk. Aim 2 examines the effect modification by, or joint effects with, neighborhood and individual-level multidimensional vulnerability factors that exacerbate the cognitive risks induced by heat based on advanced epidemiological models. Aim 2 examines the association of extreme heat with blood-based AD neuropathological markers. Dr. Choi proposes to pursue these training goals and begin the proposed research within the Davis School of Gerontology at the University of Southern California, an ideal environment with abundant intellectual and structural resources, training opportunities, and interdisciplinary researchers in ADRD, environmental health, and the biology of aging. This project works towards reducing emerging climate hazards for ADRD risk by elucidating the neurobiological and social pathways leading to individual differences in neurocognitive risks from neighborhood climate environments. It aligns with the NIA’s goal to address the exposome in ADRD and offers new insights into multi-level intervention strategies to mitigate risk among the most vulnerable populations.
