Abstract
Background Exercise likely has numerous, meaningful benefits for brain and cognition. However, those benefits and their causes remain imprecisely defined, especially in the context of cognitive disorders associated with aging, such as Alzheimer’s disease (AD). If the brain does benefit from exercise it does so primarily through exposure to brief, “acute” exposures to exercise over a lifetime. Methods: The Dementia Risk and Dynamic Response to Exercise (DYNAMIC) clinical trial seeks to characterize the acute exercise response in cerebral perfusion, and circulating neurotrophic factors in older adults with and without the apolipoprotein e4 genotype (APOE4), the strongest genetic predictor or sporadic, late onset AD. DYNAMIC will enroll 60 older adults into a single moderate intensity bout of exercise intervention. We will measure pre- and post-exercise cerebral blood flow using arterial spin labeling, and neurotrophic factors. We expect that APOE4 carriers will have poor CBF regulation, i.e. slower return to baseline perfusion after exercise, and will demonstrate blunted neurotrophic response to exercise, with concentrations of neurotrophic factors positively correlating with CBF regulation. If exercise-induced changes in perfusion and circulating factors can be detected, DYNAMIC will contribute to our understanding of exercise-induced brain change and potential biomarker outcomes of exercise interventions. Results: Preliminary proof-of-concept findings on 7 older adults and 9 younger adults. We have found that this experimental method can capture CBF and neurotrophic response over a time course, and best practices following exercise. Conclusions: This methodology will provide important insight into acute exercise response and potential directions for clinical trial outcomes. ClinicalTrials.gov NCT04009629
Competing Interest Statement
The authors have declared no competing interest.
Clinical Trial
NCT04009629
Funding Statement
Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under award number R21AG061548 and P30 AG035982, an equipment grant S10 RR29577, and the Leo and Anne Albert Charitable Trust. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Leo and Anne Albert Trust, and they had no involvement in the acquisition or dissemination of the results.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
All participants have provided written informed consent approved by the University of Kansas Institutional Review Board, consistent with the Declaration of Helsinki. Institutional Organization #: IORG0000100 Federalwide Assurance #: FWA00003411 KUMC IRBs IRB 1#: IRB00000161 IRB 3#: IRB00006196
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
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I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
Data Availability
Data may be obtained by contacting the corresponding author. Data will not be released prior to the closing of the trial.
Abbreviations
- AD
- Alzheimer’s disease
- APOE4
- apolipoprotein e4
- CBF
- cerebral blood flow
- TCD
- transcranial Doppler
- BDNF
- Brain Derived Neurotrophic Factor
- VEGF
- Vascular Endothelia Growth Factor
- IGF1
- Insulin-like Growth Factor 1
- AUC
- area under the curve
- KU ADC
- University of Kansas Alzheimer’s Disease Center
- MRI
- magnetic resonance imaging
- TGSE
- turbo gradient spin echo
- pCASL
- pseudo-continuous arterial spin labeling
- MPRAGE
- magnetization prepared rapid gradient echo
- CTCAE
- Common Terminology Criteria for Adverse Events
- DSMC
- Data and Safety Monitoring Committee
- PET
- positron emission tomography