Clinical trial NCT04009629: Dementia Risk and Dynamic Response to Exercise
Official title: Dementia Risk and Dynamic Response to Exercise
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alzheimer Disease 2 Due to Apoe4 Isoform
Healthy Aging
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2019-07-05
Enrollment: 61
Sex: ALL
Minimum age (years): 65
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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)
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Cerebral Blood Flow Area Under Curve
timeFrame: ~24 minutes
Secondary outcomes:
measure: Insulin-like Growth Factor-1 Change
timeFrame: Pre-to-post intervention (~15 minutes)
measure: Vascular Endothelial Growth Factor Change
timeFrame: Pre-to-post intervention (~15 minutes)
measure: Brain Derived Neurotrophic Factor Change
timeFrame: Pre-to-post intervention (~15 minutes)
Other outcomes:
Locations:
city: Fairway
country: United States
facility: University of Kansas Alzheimer's Disease Center
state: Kansas
Study officials:
affiliation: University of Kansas Medical Center
name: Eric D Vidoni, PT, PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.