Dementia Risk and Dynamic Response to Exercise

Not Applicable

Completed

Conditions: Healthy Aging
Alzheimer Disease 2 Due to Apoe4 Isoform

Interventions: Behavioral: Moderate Intensity Aerobic Exercise

Registration Number: NCT04009629

Lead Sponsor: University of Kansas Medical Center

Brief 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 61

Inclusion Criteria

Age 65-85
English speaking
Normal or corrected hearing or vision,
Without activity restrictions.

Exclusion Criteria

Clinically significant cognitive or psychiatric illness,
Anti- coagulant use,
High cardiovascular risk without physician clearance for exercise,
Exercise-limiting musculoskeletal condition,
MRI contraindications

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Exercise - apolipoprotein e4 carrier	Moderate Intensity Aerobic Exercise	A single 15 minute bout of moderate intensity aerobic exercise for individuals with 1 or 2 copies of the APOE4 allele, the leading genetic risk factor for late-onset Alzheimer's dementia.
Exercise - apolipoprotein e4 non-carrier	Moderate Intensity Aerobic Exercise	A single 15 minute bout of moderate intensity aerobic exercise for individuals with 0 copies of the APOE4 allele, the leading genetic risk factor for late-onset Alzheimer's dementia.

Primary Outcome Measures

Name	Time	Method
Cerebral Blood Flow Area Under Curve	~24 minutes	Cumulative cerebral blood flow measured by Arterial Spin Labeling MRI. The standard arterial spin labeling unit of measure is average milliliters per 100 grams of tissue per minute (mL/100g tissue/minute). For the present analysis, we summed perfusion over the entire acquisition period, 23.2 minutes, rather than averaging. Therefore the units are milliliters per 100 grams of tissue

Secondary Outcome Measures

Name	Time	Method
Insulin-like Growth Factor-1 Change	Pre-to-post intervention (~15 minutes)	Change in circulating Insulin-like Growth Factor-1 from pre-to-post exercise
Vascular Endothelial Growth Factor Change	Pre-to-post intervention (~15 minutes)	Change in circulating Vascular Endothelial Growth Factor from pre-to-post exercise
Brain Derived Neurotrophic Factor Change	Pre-to-post intervention (~15 minutes)	Change in circulating Brain Derived Neurotrophic Factor from pre-to-post exercise