Dementia Risk and Dynamic Response to Exercise

NCT ID: NCT04009629

Last Updated: 2022-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-25
• Study Completion Date: 2021-10-28

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.

Conditions

Alzheimer Disease 2 Due to Apoe4 Isoform; Healthy Aging

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Exercise - apolipoprotein e4 carrier

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.

Group Type: EXPERIMENTAL

Moderate Intensity Aerobic Exercise

Intervention Type: BEHAVIORAL

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.

Exercise - apolipoprotein e4 non-carrier

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.

Group Type: EXPERIMENTAL

Moderate Intensity Aerobic Exercise

Intervention Type: BEHAVIORAL

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.

Interventions

Moderate Intensity Aerobic Exercise

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.

Intervention Type: BEHAVIORAL

Eligibility Criteria

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

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

University of Kansas Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eric D Vidoni, PT, PHD

Role: PRINCIPAL_INVESTIGATOR

University of Kansas Medical Center

Locations

University of Kansas Alzheimer's Disease Center

Fairway, Kansas, United States

Countries

United States

References

Vidoni ED, Morris JK, Palmer JA, Li Y, White D, Kueck PJ, John CS, Honea RA, Lepping RJ, Lee P, Mahnken JD, Martin LE, Billinger SA. Dementia risk and dynamic response to exercise: A non-randomized clinical trial. PLoS One. 2022 Jul 8;17(7):e0265860. doi: 10.1371/journal.pone.0265860. eCollection 2022.

Reference Type: DERIVED

PMID: 35802628 (View on PubMed)

White D, John CS, Kucera A, Truver B, Lepping RJ, Kueck PJ, Lee P, Martin L, Billinger SA, Burns JM, Morris JK, Vidoni ED. A methodology for an acute exercise clinical trial called dementia risk and dynamic response to exercise. Sci Rep. 2021 Jun 17;11(1):12776. doi: 10.1038/s41598-021-92177-0.

Reference Type: DERIVED

PMID: 34140586 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R21AG061548

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00142822

Identifier Type: -

Identifier Source: org_study_id