A methodology for an acute exercise clinical trial called dementia risk and dynamic response to exercise

Dreu White, Casey S John, Ashley Kucera, Bryce Truver, Rebecca J Lepping, Paul J Kueck, Phil Lee, Laura Martin, Sandra A Billinger, Jeffrey M Burns, Jill K Morris, Eric D Vidoni, Dreu White, Casey S John, Ashley Kucera, Bryce Truver, Rebecca J Lepping, Paul J Kueck, Phil Lee, Laura Martin, Sandra A Billinger, Jeffrey M Burns, Jill K Morris, Eric D Vidoni

Abstract

Exercise likely has numerous benefits for brain and cognition. However, those benefits and their causes remain imprecisely defined. If the brain does benefit from exercise it does so primarily through cumulative brief, "acute" exposures over a lifetime. 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 of sporadic, late onset Alzheimer's disease. DYNAMIC will enroll 60 older adults into a single moderate intensity bout of exercise intervention, measuring pre- and post-exercise cerebral blood flow (CBF) 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. Preliminary findings on 7 older adults and 9 younger adults demonstrate that the experimental method can capture CBF and neurotrophic response over a time course. This methodology will provide important insight into acute exercise response and potential directions for clinical trial outcomes.ClinicalTrials.gov NCT04009629, Registered 05/07/2019.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Age-dependent resistance and cadence decision algorithm for standardizing workload to achieve target heart rate.
Figure 2
Figure 2
Study flow and average time for each study event.
Figure 3
Figure 3
Preliminary proof-of-concept findings demonstrating our ability to capture gray matter cerebral blood flow (CBF) changes post-exercise. Solid lines represent the age group mean of the cerebral blood flow (CBF) signal for each labeled-control image pair with reference to the left hand ordinate. Shaded regions show the range of CBF for each age group. Dashed lines represent mean arterial pressure over the MRI timecourse. Darker lines and shading indicate the older adult cohort. Lighter lines and shading indicate the younger adult cohort. Figure created with the ggplot2 package (ver. 3.3.3) operating under open source R version 4.0.5 (2021-03-31).

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