Association between cardiorespiratory fitness and cerebrovascular reactivity to a breath-hold stimulus in older adults: influence of aerobic exercise training

Abstract

Cerebrovascular reactivity (CVR) to a physiological stimulus is a commonly used surrogate of cerebrovascular health. Cross-sectional studies using blood oxygen level dependent (BOLD) neuroimaging demonstrated lower BOLD-CVR to hypercapnia among adults with high compared with lower cardiorespiratory fitness (CRF) in contrast to transcranial Doppler studies. However, whether BOLD-CVR changes following chronic aerobic exercise in older, cognitively intact adults is unclear. This study evaluated relations between BOLD-CVR with CRF (V̇o_2peak) using a cross-sectional and interventional study design. We hypothesized that 1) greater CRF would be associated with lower BOLD-CVR in older adults (n = 114; 65 ± 6.5 yr) with a wide range of CRF and 2) BOLD-CVR would be attenuated after exercise training in a subset (n = 33) randomized to 3-mo of moderate- or light-intensity cycling. CVR 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 analysis for cortical networks. In the cross-sectional analysis, there was a quadratic relation between V̇o_2peak (P = 0.03), but not linear (P = 0.87) and cortical BOLD-CVR. BOLD-CVR increased until a V̇o_2peak ∼28 mL/kg/min after which BOLD-CVR declined. The nonlinear trend was consistent across all networks (P = 0.04-0.07). In the intervention, both the active and light-intensity exercise groups improved CRF similarly (6% vs. 10.8%, P = 0.28). The percent change in CRF was positively associated with change in BOLD-CVR in the default mode network only. These data suggest that BOLD-CVR is nonlinearly associated with CRF and that in lower-fit adults default mode network may be most sensitive to CRF-related increases in BOLD-CVR.NEW & NOTEWORTHY Earlier studies evaluating associations between cardiorespiratory fitness (CRF) and cerebrovascular reactivity (CVR) have demonstrated conflicting findings dependent on imaging modality or subject characteristics in individuals across a narrow range of CRF. This study demonstrates that CRF is nonlinearly associated with CVR measured by blood oxygen level dependent (BOLD) fMRI in a large sample of middle-aged and older adults across a wide range of CRF, suggesting that conflicting prior findings are related to the range of CRFs studied.

Keywords: aerobic exercise training; aging; brain; cardiorespiratory fitness; cerebrovascular reactivity.

Graphical abstract

Figure 1.

A: schematic of the three phases of the breath-hold task paradigm. The sequence of events was shown slide by slide for times shown and repeated seven times. B: whole brain statistical maps showing the evoked blood oxygen level dependent (BOLD) response to the breath-hold relative to baseline comprising normal and paced breathing. Statistical maps are thresholded at z = 4.26, P < 0.05 cluster extent; the cross-hairs indicate the voxel of peak response in the posterior cingulate cortex; images are in radiological orientation so R = L. The colormaps illustrate the network masks from the Yeo/Schaefer 7 network parcellation, including the visual (red), somatomotor (blue), default (yellow), and salience/ventral attention (purple) networks, and their corresponding average percent signal change (C) reflecting cortical cerebrovascular reactivity (CVR) with each dot representing an individual in study 1 (n = 103).

Figure 2.

Scatterplots displaying the relationship between cardiorespiratory fitness (CRF) and cerebrovascular reactivity (CVR) in cross-sectional (study 1 n = 103; assessed using mixed models adjusting for covariates) and intervention (study 2 n = 28; assessed using repeated measures ANOVA) data. A: cross-sectional data with a wide spectrum of CRF showed a quadratic relation between relative and absolute V̇o_2peak with cortical CVR. B: within the default network, the relationship was stronger for absolute CRF, with weight adjusted in the regression rather than as a ratio (see Tables 2 and 3). C: in lower-fit older adults, training-related change in CRF was observed for all participants (gray lines reflect individuals and error bars reflect SE); increased CRF was related to increased CVR specifically in default mode network (see Table 4). In all plots, shaded area reflects 95% confidence interval.