PROJECT SUMMARY The overarching goal of this project is to use a novel virtual reality (VR) physical and cognitive intervention aimed at improving brain health and cognition in older adults with mild cognitive impairment (MCI), a risk factor for Alzheimer's disease (AD). AD is the most common cause of cognitive impairment in older adults and affects 36 million people worldwide. Results from several large pharmacological trials have been sobering with no effective treatments for halting, slowing, or preventing the disease. Exercise has emerged as an exciting, lifestyle intervention to help mitigate cognitive loss or delay the onset of dementia. However, to fully leverage exercise benefits in this at-risk population, training the brain to learn and engage in a cognitively- stimulating and physically-demanding environment may be key to effective therapies. Controlled cognitively- challenging environments created in a VR setting provide an adaptable and safe environment for improving cognitive dysfunction in older adults at risk for AD. While a large body of literature has found that exercise enhances cognition, very few studies have coupled physical and cognitive activity in a VR environment, simultaneously. By engaging and challenging spatial memory during moderate-to-vigorous intensity exercise over time, memories for newly acquired information may be stronger and longer-lasting than either physical or cognitive activity alone. Therefore, in this project, we aim to use an integrated, ecologically valid, and meaningful physical and cognitive intervention in VR that targets the hippocampus, a key region of interest in older adults at risk for AD. We will recruit and randomize 150 older adults to participate in the intervention (combined physical and cognitive VR program), active control (physical cycling only), or passive control (cognitive VR only) group to investigate changes in cognition, brain function, blood-based biomarkers, and physical health in old adults (55-80 years old) with early mild cognitive impairment. Results from this study will provide new evidence for the benefits of a novel combined VR intervention that target physical and cognitive health, simultaneously.