Effects of exercise training on brain metabolism and cognitive functioning in sleep apnea

Linda M Ueno-Pardi, Fabio L Souza-Duran, Larissa Matheus, Amanda G Rodrigues, Eline R F Barbosa, Paulo J Cunha, Camila G Carneiro, Naomi A Costa, Carla R Ono, Carlos A Buchpiguel, Carlos E Negrão, Geraldo Lorenzi-Filho, Geraldo Busatto-Filho, Linda M Ueno-Pardi, Fabio L Souza-Duran, Larissa Matheus, Amanda G Rodrigues, Eline R F Barbosa, Paulo J Cunha, Camila G Carneiro, Naomi A Costa, Carla R Ono, Carlos A Buchpiguel, Carlos E Negrão, Geraldo Lorenzi-Filho, Geraldo Busatto-Filho

Abstract

Impaired glucose metabolism reflects neuronal/synaptic dysfunction and cognitive function decline in patients with obstructive sleep apnea (OSA). The study investigated the extent to which exercise training (ET) improves cerebral metabolic glucose rate (CMRgl) and cognitive function in patients with OSA. Patients with moderate to severe OSA were randomly assigned to ET (3 times/week, n = 23) or no intervention (control, n = 24). Echocardiography and apolipoprotein ε4 (APOEε4) genotyping were obtained at baseline. Both groups underwent cardiopulmonary exercise testing, polysomnography, cognitive tests, brain magnetic resonance imaging, and 18F-fluoro-2-deoxy-D-Glucose positron emission tomography (18FDG-PET) at baseline and study end. Compared with control, exercise-trained group had improved exercise capacity, decreased apnea-hypopnea index (AHI), oxygen desaturation and arousal index; increased attention/executive functioning, increased CMRgl in the right frontal lobe (P < 0.05). After ET an inverse relationships occurred between CMRgl and obstructive AHI (r = - 0.43, P < 0.05) and apnea arousal index (r = - 0.53, P < 0.05), and between the changes in CMRgl and changes in mean O2 saturation during sleep and non-rapid eye movement sleep (r = - 0.43, P < 0.05), desaturation during arousal (r = - 0.44, P < 0.05), and time to attention function testing (r = - 0.46, P < 0.05). ET improves OSA severity and CMRg in the frontal lobe, which helps explain the improvement in attention/executive functioning. Our study provides promising data that reinforce the growing idea that ET may be a valuable tool to prevent hypoxia associated with decreased brain metabolism and cognitive functioning in patients with moderate to severe OSA.Trial registration: NCT02289625 (13/11/2014).

Conflict of interest statement

The authors declare no competing interests.

© 2022. The Author(s).

Figures

Figure 1
Figure 1
Profile of a randomized clinical trial showing the progress of patients throughout the trial. AHI, apnea–hypopnea index; MRI, magnetic resonance image; OSA, obstructive sleep apnea.
Figure 2
Figure 2
(A–C) Changes in cognitive performance in patients with obstructive sleep apnea in the control group and exercise-trained group. CSWT, Stroop Color Word Test; FAB, Frontal Assessment Battery; TMT, Trail Making Test. *P < 0.05 control versus training group.
Figure 3
Figure 3
Findings showing clusters of changes in cerebral metabolic glucose rate (CMRgl) in the frontal lobe of the right hemisphere highlighted in yellow in exercise-trained and control patients with obstructive sleep apnea. Foci of significance are overlaid on sagittal, coronal, and axial brain slices spatially normalized in MNI space. All voxel clusters shown in the figures retained statistical significance after family-wise error correction for multiple comparisons (P < 0.005), corrected for multiple comparison over right frontal lobe and had a minimum extent threshold of 20 voxels. Statistical details are given in Table 4. The colored bar represents F-values. The model includes APOE ε4 allele and time interval between magnetic resonance data collection as covariates. R = right.
Figure 4
Figure 4
(A) Normalized cerebral metabolic glucose rate (CMRgl) peak values (voxel values extracted from the coordinate of maximal significance) within and between control and exercise-trained groups; (B) Delta changes in CMRgl peak values in patients with obstructive sleep apnea in the control group and exercise-trained group. +P < 0.05 Significant difference compared with respective baseline values (2-way ANOVA). *P < 0.05 Control versus training group (Unpaired t test).

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