Dementia Risk and Dynamic Response to Exercise
Condition: Alzheimer Disease 2 Due to Apoe4 Isoform; Healthy Aging
MeSH terms: Alzheimer Disease; Dementia
Study type: Interventional

Summary: 
      Research suggests that physical exercise supports brain health and cognition as we age. The
      goal of this project is to examine the specific changes in brain blood flow and biological
      factors in the blood immediately after exercise in older adults who have the APOE4 gene, a
      genetic risk factor for developing Alzheimer's. Results from this study will help researchers
      and clinicians understand and measure changes in the body and brain as a function of
      exercise, and how those changes relate to Alzheimer's risk.
    

Detailed description: 
      The brain and cardiovascular system share common risk factors for age-related diseases such
      as hypertension, hypercholesterolemia, and genetics (e.g. APOE4). Because of this link, much
      work has focused on the role of cerebrovascular health in reducing dementia risk. Regular
      aerobic exercise has well-established benefits for cardiovascular health and has been
      repeatedly linked to better cognition, brain health, and lower risk of Alzheimer's disease
      (AD). Despite strong evidence for sustained cognitive and brain outcomes, the mechanisms
      relating aerobic exercise with brain health and cognition remain imprecisely defined. Amongst
      many potential mechanisms, cerebral blood flow (CBF) and blood-based biomarkers, such as
      neurotrophins, are promising targets for their shared association to brain and cardiovascular
      health. Prior investigations have largely attempted to measure change in these mechanisms
      under resting conditions after an extended exercise intervention with mixed and conflicting
      results. Further, studies have often not accounted for genetic differences that may blunt the
      effect of exercise. Unlike prior work, our innovative approach is to begin by characterizing
      the dynamic changes that result from an acute exercise challenge. A single bout of aerobic
      exercise temporarily increases CBF and prompts neurotrophin release. These transient changes
      ultimately drive long-term physiologic adaptation to exercise. Therefore, the study team will
      characterize the dynamic response to an acute, standardized bout of aerobic exercise in a
      group of nondemented older adults, comparing those who do and do not carry the APOE4 allele.
      The first aim will test if CBF response to an acute exercise challenge is blunted in APOE4
      carriers. The second aim will similarly test the acute exercise response of blood-based
      biomarkers such as brain derived neurotrophic factor, insulin-like growth factor, and
      vascular endothelial growth factor in APOE4 carriers versus non-carriers. The study team
      expects that more accurately understanding the acute effects will provide valuable insight
      into how aerobic exercise supports cognitive function and brain health. Armed with this
      knowledge the field can optimize biomarker measurement for future exercise intervention
      randomized controlled trials, informing our long-term goal of identifying precision exercise
      prescription for AD prevention.
    

Intervention name(s): Moderate Intensity Aerobic Exercise
Intervention type(s): Behavioral
Intervention description(s): Participants will exercise for 15 minutes in a moderate age-predicted heart rate range. The study team will employ an exercise device such as a treadmill, cycle, or recumbent stepper to maintain control over workload.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Single visit, case-control study identified as an intervention due to the use of a single bout of aerobic exercise under NIH rules (grants.nih.gov/policy/clinical-trials/definition.htm)
Masking: None (Open Label)
Primary purpose: Basic Science