Cardiorespiratory Fitness Attenuates the Deleterious Effects of Sleep Apnea on Cerebral Structure and Perfusion in the Wisconsin Sleep Cohort Study

Article type: Research Article

Authors: Edmunds, Kyle J.^{a; *} | Driscoll, Ira^{a; b} | Hagen, Erika W.^c | Barnet, Jodi H.^c | Ravelo, Laurel A.^c | Plante, David T.^d | Gaitán, Julian M.^a | Lose, Sarah R.^a | Motovylyak, Alice^a | Bendlin, Barbara B.^e | Okonkwo, Ozioma C.^a | Peppard, Paul E.^c

Affiliations: [a] Wisconsin Alzheimer’s Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA | [b] Psychology Department, University of Wisconsin-Milwaukee, Madison, WI, USA | [c] Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA | [d] Department of Psychiatry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA | [e] Wisconsin Alzheimer’s Institute, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA

Correspondence: [*] Correspondence to: Kyle J. Edmunds, 600 Highland Ave J5/1 Mezzanine, Madison, WI 53792, USA. Tel.: +1 414 241 8313; E-mail: [email protected].

Abstract: Background:Emerging evidence suggests that age-related changes in cerebral health may be sensitive to vascular risk modifiers, such as physical activity and sleep. Objective:We examine whether cardiorespiratory fitness modifies the association of obstructive sleep apnea (OSA) severity with MRI-assessed measures of cerebral structure and perfusion. Methods:Using data from a cross-sectional sample of participants (n = 129, 51% female, age range 49.6-85.3 years) in the Wisconsin Sleep Cohort study, we estimated linear models of MRI-assessed total and regional gray matter (GM) and white matter (WM) volumes, WM hyperintensity (WMH:ICV ratio), total lesion volume, and arterial spin labeling (ASL) cerebral blood flow (CBF), using an estimated measure of cardiorespiratory fitness (CRF) and OSA severity as predictors. Participants’ sleep was assessed using overnight in-laboratory polysomnography, and OSA severity was measured using the apnea-hypopnea index (AHI), or the mean number of recorded apnea and hypopnea events per hour of sleep. The mean±SD time difference between PSG data collection and MRI data collection was 1.7±1.5 years (range: [0, 4.9 years]). Results:OSA severity was associated with reduced total GM volume (β=-0.064; SE = 0.023; p = 0.007), greater total WM lesion volume (interaction p = 0.023), and greater WMHs (interaction p = 0.017) in less-fit subjects. Perfusion models revealed significant differences in the association of AHI and regional CBF between fitness groups (interaction ps < 0.05). Conclusion:This work provides new evidence for the protective role of cardiorespiratory fitness against the deleterious effects of OSA on brain aging in late-middle age to older adults.

Keywords: Alzheimer’s disease, cardiorespiratory fitness, cerebral perfusion, gray matter, obstructive sleep apnea, white matter

DOI: 10.3233/JAD-220910

Journal: Journal of Alzheimer's Disease, vol. 95, no. 2, pp. 427-435, 2023