Higher Cardiorespiratory Fitness is Associated with Lower Cerebrovascular Reactivity in Older Adults Independent of Age and Aortic Stiffness
Authors: DuBose Lyndsey E. , Voss Michelle W. , Weng Timothy B. , Dubishar Kaitlyn , Lane‐Cordova Abbi , Sigurdsson Gardar , Schmid Phillip G. , Pierce Gary L. 
Published: November 2023

IntroductionHabitual aerobic exercise training is associated with preserved cognition, higher cerebrovascular reactivity (CVR) via experimental hypercapnia and transcranial Doppler, lower aortic stiffness and higher white matter brain volumes in older adults. However, global CVR assessed via functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) responses to steady‐state hypercapnia was recently demonstrated to be paradoxically reduced in masters athletes compared with sedentary older adults (Thomas, Binu P., et al., 2013). Given this, it is unknown if functional BOLD‐dependent CVR would be associated with maximal exercise oxygen uptake (VO2max) in sedentary and recreationally active healthy older adults. We hypothesized that healthy older adults with higher compared with lower cardiorespiratory fitness would have lower CVR and that CVR would be associated with white matter integrity (WMI), cognitive performance and aortic stiffness.MethodsThirty‐two older adults (range 50–71 yrs; mean 64 ± 0.8 yrs; BMI 26 ± 0.6 kg/m2) without cardiovascular disease or cognitive impairment were studied. BOLD (3T MRI) imaging was used to measure CVR (i.e., BOLD signal change) in response to an acute physiological hypercapnic stimulus using a blocked end‐tidal breath hold design. Regional CVR was analyzed using region‐of‐interest (ROI) and voxelwise (FEAT, FSL) approaches and regional WMI was assessed by fractional anisotropy (FA, 3T MRI). All subjects completed a graded exercise test to volitional fatigue on a cycle ergometer to assess VO2max. Aortic stiffness and carotid blood pressure were determined by carotid‐femoral pulse wave velocity (cfPWV) and pulse wave analysis via non‐invasive tonometry. Cognitive performance was tested by N‐Back and letter/ pattern comparison tasks testing working memory and processing speed, respectively.ResultsIn the entire cohort, VO2max was inversely associated with frontal (r=−0.43, P<0.05), occipital (r=−0.46, P=0.05), parietal (r=−0.46, P=0.01), thalamus (r=−0.44, P=0.01) and temporal (r=−0.44, P<0.05) lobe CVR using the lobular but not voxelwise approach. In a subset of the cohort (n=13) including the very highest (HF, n=5) and very lowest fit (LF, n=8) based on published normative VO2max values, CVR in all regions was lower in HF compared with LF older adults (Table 2). Age, BMI, brachial and carotid blood pressure, cfPWV, cognitive performance and WMI did not differ between HF and LF adults (Table 1). In this subset, greater VO2 max was associated with lower regional CVR in the frontal (r=−0.70, P<0.01), insula (r=−0.56, P<0.05), occipital (r=−0.73, P<0.01), parietal (r=−0.78, P<0.05), thalamus (r=−0.70, P=0.001) and temporal lobes (r=−0.73, P<0.01) using the lobular ROI approach and confirmed by the voxelwise analysis. Regional CVR was not related to age, performance on the N‐Back and letter/ pattern comparison tasks, cfPWV, or regional WMI among the HF, LF, or the entire cohort.ConclusionsRegional CVR in response to an acute hypercapnic stimulus (breath hold) is inversely related to VO2max in older healthy adults. CVR is reduced in HF compared with LF older adults in the absence of differences in age, aortic stiffness, WMI and cognitive performance. Further studies are needed to determine if chronic aerobic exercise potentially reduces chemoreceptor sensitivity to physiological hypercapnia therefore underestimating CVR in exercise‐trained older adults.Support or Funding InformationSupported by NIH grants 1R21 AG043722, U54 TR001013 and 5KL2 RR24980‐5.
Subject characteristics of subset (n=13) of low and high fit older adults.

Low Fit (n=8)
High Fit (n=5)
p‐value

Males/Females
2/6
3/2

Age
65.0 ± 1.7
65.8 ± 2.1
0.77

Body mass index (kg/m2)
28.7 ± 1.4
22.6 ± 1.5
0.08

VO2max (ml/kg/min)
24.0 ± 1.7
38.5 ± 1.4
<0.05

Carotid systolic BP (mmHg)
119 ± 10
117 ± 7
0.87

Carotid PP (mmHg)
46 ± 7
44 ± 4
0.80

Carotid augmentation index (%)
13.2 ± 2.9
8.4 ± 4.1
0.37

Brachial systolic BP (mmHg)
125 ± 6
125 ± 7
0.98

Brachial PP (mmHg)
51 ± 7
53 ± 5
0.87

Carotid‐femoral PWV (m/sec)
8.9 ± 0.8
7.6 ± 0.4
0.21

2‐Back Average Accuracy (%)
0.81 ± 0.1
0.62 ± 0.1
0.11

Letter comparison (#/21)
11.6 ± 1.0
10.9 ± 1.1
0.63

Pattern comparison (#/30)
16.9 ± 1.0
17.4 ± 1.3
0.78

Data are mean ± SE. VO2max, maximal exercise oxygen uptake; BP, blood pressure. PP, pulse pressure. PWV, pulse wave velocity.

Regional CVR (MRI BOLD response to breath hold) in highest and lowest fit older adults.

Low Fit (n=8)
High Fit (n= 5)
p‐value

Frontal
1.27 ± 0.1
0.59 ± 0.1
<0.001

Insula
0.90 ± 0.1
0.62 ± 0.1
<0.05

Occipital
1.50 ± 0.1
0.68 ± 0.2
<0.001

Parietal
1.41 ± 0.1
0.68 ± 0.1
<0.001

Thalamus
1.43 ± 0.1
0.84 ± 0.1
<0.01

Temporal
1.37 ± 0.1
0.50 ± 0.2
<0.001

Data are mean ± SE.