Chronic Aerobic Exercise Training Reduces Cerebrovascular Reactivity to a Breath Hold Stimulus in Middle‐aged and Older Adults
Authors: DuBose Lyndsey E. , Wharff Conner , Schmid Phillip , Muellerleile Michael , Sigurdsson Gardar , Reist Lauren , Pierce Gary L. , Voss Michelle W. 
Published: June 2021

IntroductionHabitual aerobic exercise is hypothesized to attenuate age‐related declines in cognitive performance mediated in part by alterations in cerebrovascular reactivity (CVR). However, cross‐sectional studies using fMRI blood oxygen level dependent (BOLD) imaging demonstrate paradoxically lower CVR (cerebral blood flow response to experimental hypercapnia) among middle‐aged and older (MA/O) adults with high compared with low aerobic fitness.1,2 It remains unknown if greater moderate‐to‐vigorous physical activity (MVPA) or initiating chronic aerobic exercise training in previously inactive MA/O adults alters CVR to hypercapnia. We hypothesized that 1) greater MVPA and cardiorespiratory fitness (VO2max) is associated with lower CVR; 2) CVR is attenuated after 3‐months of habitual aerobic exercise training in previously inactive MA/O adults.MethodsFifty‐six MA/O adults (mean ± SE: 64.5 ± 0.8 yrs, range: 50–76 yrs) were studied. VO2max was considered as a percentile based on age and sex (VO2%). CVR (3T fMRI) was quantified as the change in the BOLD signal in response to acute hypercapnia using a blocked breath hold design from a region‐of‐interest (ROI) analysis for cortical networks known to be affected by aging. Average minutes per day of MVPA (accelerometry) were measured at baseline in a subset (n = 33) to delineate the role of MVPA from VO2max. After baseline testing, the subset of MA/O adults were randomized to either 3‐months of aerobic (40 minutes/session, 3 sessions/week at ~70% HRmax) or passive exercise control training on a cycle ergometer. VO2max and fMRI testing were repeated post‐intervention. Mixed model regressions were used to test the effects of the predictors (VO2% and MVPA) on CVR, and whether this relation varied by cortical network, adjusted for covariates of interest (scanner and subject motion).ResultsIn the entire cohort, there was a quadratic relation between VO2% and CVR at baseline, shown by the significant coefficient forVO2%2 (β = −0.12 ± 0.05, p = 0.01 ) but not VO2% (β = 0.14 ± 0.08, p = 0.08), and network ROI significantly improved model fit (χ2(2) = 42.17, p < 0.001). Post‐hoc tests showed the strongest quadratic effect in the somatomotor network (β = −0.12 ± 0.06, p = 0.05). However, the general pattern was similar across ROIs; CVR increased until the 30th percentile of VO2% after which CVR declined. In the subset, baseline MVPA was not associated with CVR (p = 0.33). In the intervention cohort, CVR declined after the exercise intervention in the aerobic exercise, but not passive control, group (significant three‐way interaction term, time x VO2max x intervention, β = −0.15 ± 0.05, p = 0.008).ConclusionsModerate intensity aerobic exercise training in inactive MA/O adults may attenuate CVR to hypercapnia. Future studies are needed to determine the mechanism by which chronic aerobic exercise paradoxically reduces CVR to a physiological stimulus.Support or Funding InformationNIH 1R21 AG043722, U54 TR001013 and 5KL2 RR24980‐5This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.