Aerobic Exercise Training Improves Cerebral Blood Flow and Executive Function: A Randomized, Controlled Cross-Over Trial in Sedentary Older Men

Jordi P D Kleinloog, Ronald P Mensink, Dimo Ivanov, Jos J Adam, Kamil Uludağ, Peter J Joris, Jordi P D Kleinloog, Ronald P Mensink, Dimo Ivanov, Jos J Adam, Kamil Uludağ, Peter J Joris

Abstract

Background: Physical activity may attenuate age-related cognitive decline by improving cerebrovascular function. The aim of this study was therefore to investigate effects of aerobic exercise training on cerebral blood flow (CBF), which is a sensitive physiological marker of cerebrovascular function, in sedentary older men.

Methods: Seventeen apparently healthy men, aged 60-70 years and with a BMI between 25 and 35 kg/m2, were included in a randomized, controlled cross-over trial. Study participants were randomly allocated to a fully-supervised, progressive, aerobic exercise training or no-exercise control period for 8 weeks, separated by a 12-week wash-out period. Measurements at the end of each period included aerobic fitness evaluated using peak oxygen consumption during incremental exercise (VO2 peak), CBF measured with pseudo-continuous arterial spin labeling magnetic resonance imaging, and post-load glucose responses determined using an oral glucose tolerance test (OGTT). Furthermore, cognitive performance was assessed in the domains of executive function, memory, and psychomotor speed.

Results: VO2 peak significantly increased following aerobic exercise training compared to no-exercise control by 262 ± 236 mL (P < 0.001). CBF was increased by 27% bilaterally in the frontal lobe, particularly the subcallosal and anterior cingulate gyrus (cluster volume: 1008 mm3; P < 0.05), while CBF was reduced by 19% in the right medial temporal lobe, mainly temporal fusiform gyrus (cluster volume: 408 mm3; P < 0.05). Mean post-load glucose concentrations determined using an OGTT decreased by 0.33 ± 0.63 mmol/L (P = 0.049). Furthermore, executive function improved as the latency of response was reduced by 5% (P = 0.034), but no changes were observed in memory or psychomotor speed.

Conclusion: Aerobic exercise training improves regional CBF in sedentary older men. These changes in CBF may underlie exercise-induced beneficial effects on executive function, which could be partly mediated by improvements in glucose metabolism. This clinical trial is registered on ClinicalTrials.gov as NCT03272061.

Keywords: aging; arterial spin labeling; cerebral blood flow; cognition; exercise; glucose metabolism.

Copyright © 2019 Kleinloog, Mensink, Ivanov, Adam, Uludağ and Joris.

Figures

FIGURE 1
FIGURE 1
Perfusion-weighted image acquired using pseudo-continuous arterial spin labeling that we generated at the Scannexus research facilities in Maastricht. The images show the cerebral blood flow (CBF) in mL/100 g tissue/min (scale shown by color bar). (A) Sagittal slice including angiogram from vertebral and carotid artery, coronal slice, and axial slice. The yellow rectangular boxes represent the imaging box and labeling plane perpendicular to the arteries. (B) Mean CBF map from all participants (n = 14) after the control period. Data from a randomized, controlled crossover study with sedentary older men.
FIGURE 2
FIGURE 2
CONSORT flow diagram. Diagram of the progress through the phases of this randomized, controlled crossover study with sedentary overweight or slightly obese older men.
FIGURE 3
FIGURE 3
Data from a randomized, controlled crossover study with sedentary overweight or slightly obese older men (n = 17). Data were analyzed using linear mixed models on the difference between each timepoint with baseline. (A) Mean (±SEM) difference in peak oxygen consumption (VO2peak) and (B) maximal power (Pmax) difference during the maximal exercise. Maximal exercise tests were performed every 2 weeks during the intervention period. During the control period, maximal exercise tests were performed at baseline, after 4 weeks and after 8 weeks. Baseline values were not significantly different. There was a significant treatment ∗ time interaction for VO2peak (P = 0.018) and Pmax (P < 0.001). After Bonferroni correction there was a significant difference between control and intervention period at 4 weeks (#P = 0.006) and at 8 weeks for VO2peak and Pmax (∗P < 0.001). (C) Mean (±SEM) difference in glucose concentrations during a 7-point oral glucose tolerance test (OGTT) test. There was a significant treatment effect for glucose concentration (P = 0.049).
FIGURE 4
FIGURE 4
Results of voxel-wise comparisons including all acquired cerebral blood flow (CBF) data in three dimensional MNI template from a randomized, controlled crossover study with sedentary overweight, or slightly obese older men (n = 14). CBF increased bilaterally after the intervention compared to the control period P < 0.05 (Family-wise error corrected). The CBF of cluster 1 and 2 increased after the intervention period compared to the control with 6.39 mL/100 g tissue/min (volume: 392 mm3) and 6.95 mL/100 g tissue/min (volume: 616 mm3), respectively. The CBF of cluster 3 decreased with 4.4 mL/100 g tissue/min (volume: 408 mm3).

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