A Pilot Trial of High-Intensity Exercise to Combat Vascular and Cognitive Dysfunction in Older Adults with HIV. - PROJECT SUMMARY/ABSTRACT This K01 Mentored Research Scientist Career Development Award will facilitate Dr. Jones’ long-term career goal of conducting translational research focusing on the vascular contribution to cognitive aging in vulnerable populations, namely individuals living with HIV who are at risk of cardiovascular disease and neurocognitive impairment, and the benefits of exercise interventions. As age and HIV have independent and synergistic effects on the brain, it places older people living with HIV (OPWH) at an increased risk of HIV-associated neurocognitive disorder and Alzheimer’s disease and related dementias. Accelerated vascular aging, assessed via arterial stiffness, is likely linked to those neurocognitive changes and exercise may be an effective, nonpharmacological strategy to counterbalance the adverse vascular effects contributing to neurocognitive disorders. The candidate is an exercise physiologist with a strong background in research on aging and vascular health and function. The proposed research and career development plan builds directly on my prior experiences to assess vascular health and function in aging, vulnerable populations. In line with the NIA’s Strategic Directions of developing effective interventions to reduce the burden of age-related conditions, the proposed pilot/feasibility study will explore the impact of high-intensity exercise on arterial stiffness and cognitive functioning among OPWH who have neurocognitive disorders, and refine and finalize elements critical to conducting future, fully powered randomized controlled trials (RCTs). Specific Aim 1 will evaluate the feasibility (i.e., safety, adherence, retention) and preliminary impact of 12 weeks of high-intensity exercise compared with continuous moderate exercise on arterial stiffness and cognition. Specific Aim 2 will be guided by the Theoretical Domains Framework to qualitatively assess the baseline barriers to engagement in exercise and the participant experiences of the exercise intervention. This award will enhance Dr. Jones’ career development to conduct future, large-scale RCTs by 1) enhancing his proficiency in HIV and HIV-comorbidity research, 2) developing expertise in HIV-associated neurocognitive impairment and assessment, 3) advancing knowledge of exercise clinical trial development and implementation, and 4) attaining skills in qualitative research methods to understand barriers to engagement and participant experiences. Dr. Jones’ mentorship team is well-suited to facilitate the research and career development plan, with combined expertise in HIV, cognition, exercise clinical trials, and qualitative methodology.