Exercise Training to Improve Brain Health in Older HIV+ Individuals

Washington University School of Medicine75 enrolled

Overview

Management and treatment of older persons living with HIV (PLWH) (≥ 40 years old) is becoming increasingly more complex as a majority is greater than 40 years old. This proposal will conduct a prospective controlled intervention trial to assess the quantitative and qualitative effects of a monitored aerobic/resistance exercise (EXS) program compared to a social-interaction stretching (SIS) program on brain health (neuropsychological performance testing and neuroimaging measurements) in older PLWH. These results could influence public health policy by encouraging PLWH to adopt a more physically active lifestyle and stimulate the development of effective EXS programs for older PLWH.

Management of older persons living with HIV (PLWH) (≥ 40 years old) is becoming increasingly more complex as a majority is greater than 40 years old. Attempts to improve the quality of life of older PLWH using adjunctive therapeutics to combination antiretroviral therapy (cART) have largely been unsuccessful. While the impact of physical activity on brain health (assessed by neuropsychological performance and neuroimaging) has been well studied in older healthy HIV uninfected (HIV-) individuals and neurodegenerative conditions, few studies have concentrated on older PLWH. Both clinically and pathophysiologically, HIV associated neurocognitive disorders (HAND) differs from other neurodegenerative disorders seen with aging (e.g. Alzheimer's disease (AD). A positive association relationship between exercise and cognition has been observed in PLWH, but physical activity has been primarily examined using self-report questionnaires that are subjective and not quantitative. To date, no study has focused on the direct effects of exercise on neuropsychological performance or neuroimaging in PLWH. The objective of this proposal is to conduct a prospective controlled intervention trial to determine if an increase in physical activity through a monitored aerobic and resistance exercise (EXS) program improves brain health in older PLWH. We will quantify physical function (physical activity using cardiorespiratory capacity and actigraphy) and brain function \[neuropsychological performance testing and neuroimaging (cerebral blood flow (CBF) and brain volume)\] in older physically inactive PLWH at baseline and 26 weeks after randomization to either an EXS or a social-interaction stretching (SIS) program. In addition, we will obtain stool samples, serum markers of neurogenesis, glucose regulation, and systemic inflammation. A direct impact of these expected outcomes will be the adoption of a more physically active lifestyle by older PLWH and improved EXS guidelines and programs for older PLWH.

Study Type

Interventions

ExerciseBEHAVIORAL

The resistance exercise training component will follow aerobic exercise and will consist of 4 upper and 3 lower body routines. A combination of guided-motion machines and free weights will be used. Voluntary maximum strength will be measured during the first 4 sessions on each exercise station. The program will initially consist of 1-2 sets of each exercise while lifting a weight that causes muscle fatigue after 8-10 repetitions. The trainer will monitor each participant's exercise response, and when the participant can comfortably lift the weight for 12 repetitions on any exercise, the weight will be increased to cause the muscle group to fatigue after 8 repetitions. This progressive 8-12 repetition cycle is repeated for each exercise over 26 weeks.

Stretching and Social InteractionBEHAVIORAL

Participants will receive instructions on stretching, range of motion, limbering, and toning. Activities will focus on flexibility enhancement. Along with the stretching and flexibility, this group will have a social interaction component. They will have discussions and interact with trainers and coordinators during all their sessions. These participants will be supervised by the same trainer and will receive the same amount of attention and class interaction as participants in the EXS program.

Eligibility

Sex: ALLMin age: 40 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. age \> 40 years old 2. documented history of HIV infection 3. on stable combination antiretroviral therapy (cART) for approximately 3 months with undetectable plasma HIV RNA 4. physically inactive-sedentary lifestyle (approximately \<2 hours of exercise/week) and not engaged in regular exercise for approximately 3 months prior to enrollment 5. approximately 9 years of education 6. able to have an MRI 7. able to provide written informed consent (does not have LAR, POA, etc.) Exclusion Criteria: 1. approximately \>2x/week of moderate (or greater) exercise 2. cardiovascular/cerebrovascular disease or pulmonary disease that precludes ability to safely exercise 3. significant neurological disorders (e.g. stroke, head injury with loss of consciousness for \>30 minutes, developmental learning disability 4. presence of dementia or behavioral disorders that would prevent ability to follow the protocol 5. alcohol or substance abuse/ dependence within the last 6 months (DSM-4 TR) 6. contraindications to MRI scanning (e.g. claustrophobia, pacemaker) 7. pregnant or breast-feeding 8. unable to provide written informed consent

Outcomes

Primary Outcomes

Change in Global Cognition From Baseline to Follow up, in Exercise Group vs. Stretching Group

This measure examines the global z-score which is an average of all the individual cognitive test z scores. We looked at changes in global Z-scores from baseline to follow-up (6 months). A Z-score of 0 represents the population mean. Z-scores are considered to be better when they are above the mean and represent a better outcome.

Time frame: 6 months

Changes in Brain Structural/Functional Measures in Older PLWH

The Investigators will assess if an EXS program improves brain structure and function more than a SIS program in older sedentary PLWH. Changes in brain volumetrics (total cortex volume) at baseline (BL) and 26 weeks will be compared between EXS and SIS groups.

Time frame: 26 weeks

Change in Level of Daily Activity

Investigators will examine the amount of change in daily activity based on 7-day actigraphy at baseline and then again at follow-up (26 weeks later). Daily activity is measured using an actigraph that participants wear on their wrist and it measures the amount of time spent in sedentary, slightly active, moderately active, vigorously active or very vigorously active categories.

Time frame: 6 Months