Project Summary/Abstract Memory decline is a pervasive complaint of older adults and can exact an enormous emotional, physical, and economic toll on individuals, their loved ones, and society. Meanwhile, physical inactivity is one of the most significant modifiable risk factors for dementia. Specifically, exercise and physical activity interventions appear to benefit and preserve the hippocampal subfield structures, regions that play a critical role in memory processes and are an early site of neurodegeneration and dementia progression. However, researchers and public health experts still do not know the underlying neurophysiological mechanisms by which exercise might afford these benefits. Without a comprehensive understanding of exercise's mechanistic effects on the aging brain, it remains hard to determine and implement optimized and individualized exercise training interventions. Thus, it is critical to conduct acute exercise studies using advanced neuroimaging and behavioral measures to characterize a single exercise session's underlying neurophysiological effects on the aging brain. This proposed project provides a unique training opportunity under established mentors centered on the impact of acute exercise on hippocampal subfield function and microstructure in older adults. To accomplish this, we will employ methods developed in each mentors’ laboratory, including pattern separation performance, task-based fMRI, and HARDI-based measures. The data from these cost- and time-efficient acute exercise studies can then be combined with and inform future optimized exercise training plans for older adults with memory deficits and who are at risk of cognitive decline. Previous acute exercise work has rarely used neuroimaging techniques or hippocampal subfield specific cognitive tasks, and even fewer have conducted these types of studies in older adults. Whereas previously we demonstrated that acute exercise elicits alterations in gross hippocampal function and structure, here we want to build on this work by concomitantly examining the impact of acute exercise on memory performance and hippocampal subfield function and microstructure. Therefore, the purpose of this project is to use an age-susceptible and highly hippocampal-specific pattern separation task, along with advanced functional and diffusion imaging methods to characterize the effects of acute exercise on hippocampal subfield microstructure and function in older adults following an acute bout of moderate-intensity aerobic exercise. Using these advanced imaging protocols and a highly hippocampal-specific and age-susceptible behavioral paradigm in an acute exercise intervention will help elucidate the immediate effects of aerobic exercise on important age-susceptible memory networks. The results of this study will help future clinical trials implement optimized exercise interventions and neurophysiological measures that will be informative and beneficial for understanding the effects of exercise on the aging brain. Furthermore, this training opportunity will help establish a promising trajectory as an independent scientist.

Project Narrative The ability to correctly encode and distinguish between highly similar memory representations is a critical aspect of memory function and is an early indicator of hippocampal network dysfunction in aging and various neurodegenerative diseases. This proposal seeks to explore how acute exercise affects hippocampal subfield function and microstructure in healthy older adults. This research is in line with NIA's mission of AD prevention and healthy cognitive aging by identifying the immediate functional and neurophysiological effects of exercise on a specific memory network that can then be used to help optimize exercise intervention treatments and preventive measures for memory loss in aging adults.