aeRobic Exercise and Cognitive Health
Condition: Alzheimer's Disease; Aging
MeSH terms: Alzheimer Disease
Study type: Interventional

Summary: 
      The purpose of the aeRobic Exercise and Cognitive Health (REACH) study is to understand how
      an aerobic exercise intervention might help promote brain health and cognition, thereby
      delaying the onset of clinical symptoms of Alzheimer's disease.
    

Detailed description: 
      The prevalence and costs associated with Alzheimer's disease (AD) are projected to increase
      exponentially owing to the unprecedented expansion in the elderly segment of the United
      States' population. Given this looming specter, delaying the onset of AD symptoms and curbing
      the progression of the underlying disease process has become a national public health
      imperative. Delaying symptom onset by as little as 5 years could reduce the prevalence of AD
      by half. Unfortunately, currently available drug treatments for AD are not curative.
      Similarly, clinical trials testing novel disease-modifying therapeutics have been
      disappointing. The urgency of alternative approaches for halting the global crisis posed by
      AD cannot be overstated.

      Animal studies have demonstrated that aerobic exercise (EXER) is a low-cost, low-risk
      intervention capable of altering the AD pathological process. Randomized controlled trials
      (RCTs) of EXER in older adults have also revealed its beneficial effects on AD-relevant
      measures such as brain glucose metabolism and memory/executive function. Importantly, a
      recent evidence review found that of 7 key modifiable risk factors for AD, physical activity
      had the highest impact on reducing the national prevalence of AD. However, there are
      presently no RCTs examining the effects of EXER in middle-aged, asymptomatic individuals at
      increased risk of AD. This is an important knowledge gap for several reasons. Interventions
      to halt the AD pathological cascade are more likely to be effective if implemented prior to
      pervasive neuronal damage. Secondly, persons with specific risk factors for developing AD
      (such as parental family history (FH)) represent a choice target population for any credible
      attempts at reducing the growing burden of AD. Lastly, a key limitation of prior EXER RCTs is
      the failure to adequately account for participants' physical activity levels outside of the
      intervention.

      Accordingly, the main objective of this study is to pilot a 26-week trial of EXER among
      asymptomatic, middle-aged adults with and without family history (FH) of AD enrolled in the
      Wisconsin Registry for Alzheimer's Prevention (WRAP) or the Wisconsin Alzheimer's Disease
      Research Center (WADRC). The investigators' near-term goal is to assess the feasibility and
      acceptability of this structured intervention and preliminarily evaluate (i) its effect on
      AD-relevant outcomes such as glucose metabolism and (ii) the mechanism for such effects. The
      investigators' longer-term goal is to use the data gathered via this pilot to further refine
      the intervention, estimate effect sizes for key outcomes, and seek NIH funding for a longer
      and more definitive assessment of whether EXER can effectively curtail AD progression in
      midlife. The specific aims are:

      AIM 1: Determine the feasibility and acceptability of a 26-week, 3-4 days per week,
      structured EXER regimen among middle-aged adults with FH of AD. Hypothesis: The investigators
      will successfully enroll the 30 participants (15 each in EXER and usual physical activity
      groups) targeted for this study. At least 90% of the participants within the EXER group,
      called the enhanced physical activity group, will complete ≥80% of scheduled training
      sessions.

      AIM 2: Preliminarily characterize the effect of the EXER intervention on AD-related brain
      alteration. Hypothesis: Compared to participants randomized to the usual physical activity
      group, those randomized to the enhanced physical activity group will demonstrate preserved
      brain glucose metabolism. Similar effects will be seen in secondary outcomes including
      cerebral blood flow, hippocampal volume, vascular health, memory/executive function, and
      mood.

      AIM 3: Preliminarily evaluate (i) the biological mechanisms by which EXER affects brain
      health and cognition, and (ii) the individual difference factors that potentially moderate
      EXER's effects. Hypotheses: (i) Persons in the enhanced physical activity group will exhibit
      significant increases in circulating neurotrophins and improved cardiorespiratory fitness,
      and (ii) the beneficial effects of EXER will be more pronounced for participants with
      decreased sedentary behaviors outside of the intervention (measured via accelerometry).

      AIM 4: Preliminarily determine whether EXER improves vascular health. Hypothesis: Individuals
      in the enhanced physical activity group will exhibit comparatively increased cerebral blood
      flow, and improved endothelial function.
    

Intervention name(s): Enhanced Physical Activity
Intervention type(s): Behavioral
Intervention description(s): This is a 26-week aerobic exercise intervention. The primary mode of training is treadmill walking, with the initial speed and duration calibrated to each participant's baseline aerobic capacity. Participants will train 3-4 days per week with the goal of attaining 150+ minutes of exercise per week by the seventh week. Exercise will be set between 50-60% of maximum heart rate reserve for weeks 1-4, 60-70% for weeks 5-8, and 70-80% for weeks 9-26. Exercise duration will be approximately 15-20 minutes per session during the first week and then increase by 5 minutes each week until a duration of approximately 38-50 minutes per session is reached. Each training session will begin with a 5-minute warm-up and end with a 5-minute recovery period.
Other intervention name(s): Aerobic Exercise (EXER)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Alzheimer's Disease; Dementia; aerobic exercise; physical activity; exercise; neuroimaging