Effect of High-Intensity Exercise to Attenuate Cognitive Function Limitations and Train Exercise Habits in Older People Living With HIV

Overview

People aging with HIV are at higher risk for Alzheimer's disease and related dementias, and although physical activity is a promising target to mitigate such risk, this population engages in low levels of physical activity. Few studies have tested cognitive effects of exercise interventions or examined mechanisms of adherence to long-term exercise among diverse samples of midlife and older people with HIV. The current study will leverage an existing R01 to address these gaps and provide implications for development of personalized approaches for the treatment and prevention of cognitive impairment and dementia in older people with HIV.

The population of people with HIV (PWH) is aging, and are at higher risk for Alzheimer's disease and related dementias (ADRD) than seronegative counterparts. Although physical activity (PA) is a promising protective factor to mitigate ADRD risk, few well-powered PA intervention studies have rigorously tested cognitive outcomes among older PWH, a population with rates of moderate to vigorous PA well below recommended guidelines. Further, given that adherence to habitual PA diminishes after supervised interventions, identifying mechanisms of adherence (MoA) to habitual PA among older PWH is germane to develop effective and durable interventions to protect cognitive health. The proposed R01 will leverage the High-Intensity Exercise Study to Attenuate Limitations and Train Habits in Older Adults With HIV (HEALTH), a two-site RCT (University of Washington \[UW\], University of Colorado Denver \[UCD\]) of 100 older PWH examining: 1) if 4 months of supervised high-intensity interval training (HIIT) mitigates physical function impairments and fatigue to a greater extent than continuous moderate exercise (CME); 2) the effects of a 3 month text-messaging intervention on PA adherence. In contrast to CME, where aerobic exercise is performed continuously for a specified duration, HIIT, which uses repeated alternating bouts of highintensity and lower intensity aerobic exercise, has shown superior efficacy in improving physiological and cognitive outcomes, and is associated with superior enjoyment which may increase adherence to PA regimens. The proposed R01 (HEALTH-COG) will leverage the two HEALTH sites, add a new racially diverse UAB site, and add new measures (psychological MoA measures, cognitive function assessments, biomarkers) and a few 12 month follow-up to the parent study. We estimate that of our planned sample of N=100, n=50 will be enrolled at UAB and n=50 total at UW and UCD. Our primary aim is to compare the effects of a 4 month supervised HIIT or CME intervention on (1°) cognitive functioning and (2°) subjective cognitive symptoms. Our exploratory aim is to evaluate putative biomarkers underlying the effect of PA on cognition (blood markers: e.g., BDNF, VEGF, IL-6 and neuroimaging markers: cerebral blood flow, resting state functional connectivity, and brain volume). Our secondary aim is to determine MoA to long-term PA maintenance at 12 months. This aim will examine distal predictors of long-term PA, including sociodemographic, clinical, and intervention factors (i.e., changes in parent R01 physical outcomes \[cardiorespiratory fitness\], condition \[HIIT vs CME\], \[coaching vs control\]), as well as proximal psychological MoA assessed in real-time, using EMA (e.g., self-efficacy, perceived benefits, motivation, social support). Testing efficacy and mechanisms of exercise interventions on cognitive outcomes and understanding psychological MoA of habitual PA following supervised interventions will aid in the development and implementation of personalized medicine approaches for the treatment and prevention of cognitive impairment and ADRD in older PWH.