Excessive Daytime Sleepiness Associated With Cognitive Deficits and Abnormal Brain Network Topology in Obstructive Sleep Apnea

Excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA) was associated with measurable cognitive impairment, reduced glymphatic clearance, and disrupted functional brain network organization, according to a prospective study published in the Journal of Magnetic Resonance Imaging. The findings, drawn from 102 patients with OSA and 86 healthy controls, suggest that aberrant connectivity in the bilateral middle frontal gyrus (MFG) and left inferior parietal lobule (IPL) may partially explain how EDS translates into cognitive declin.¹

OSA affects a substantial proportion of adults and is a well-established contributor to neurocognitive morbidity, with EDS reported in 40.5% to 58% of patients at diagnosis.² Although EDS has long been associated with deficits in attention, processing speed, and executive function, the neurobiological pathway linking sleepiness to cognition has remained poorly characterized.

Study Overview

Investigators prospectively recruited 102 patients with OSA (men, 86; median age, 33 years) and 86 age- and sex-matched healthy controls between June 2021 and June 2024. All participants completed the Epworth Sleepiness Scale (ESS), multiparameter MRI, and a battery of neuropsychological tests, including the number connection tests (NCT-A/B), digit symbol test, line tracing test, serial dotting test, and Stroop Color/Word test.

OSA diagnosis required overnight polysomnography, with 154 participants (OSA, n = 85, controls, n = 69) completing the full cognitive battery. MRI outcomes included the diffusion tensor imaging along the perivascular space (DTI-ALPS) index and global BOLD–cerebrospinal fluid (gBOLD–CSF) coupling, both proxies for glymphatic activity, along with resting-state functional network topology and cortical thickness.

Key Findings

Conducted by senior author Yingwei Qiu, MD, PhD, professor in the Department of Radiology at Shenzhen University in China, patients with OSA reported markedly greater daytime sleepiness than controls (ESS score, 10.00 vs 2.00; effect size, 0.74) and performed worse across multiple cognitive domains, including NCT-B, digit symbol test, and Stroop measures (effect sizes, 0.23-0.37).

OSA was also associated with a lower DTI-ALPS index (effect size, 0.25), indicating reduced subcortical glymphatic clearance, though gBOLD–CSF coupling did not differ between groups. Functional network analysis showed increased degree centrality and nodal efficiency in the bilateral MFG and left IPL, alongside decreased degree centrality in the left olfactory cortex (effect sizes, -0.80 to 0.57). No significant between-group differences emerged in cortical thickness after correction for multiple comparisons.

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ESS scores correlated significantly with poorer cognitive performance (r = -0.173 to 0.258), lower DTI-ALPS index (r = -0.199), and abnormal nodal network metrics (r = -0.364 to 0.279). Mediation analyses indicated that altered degree centrality and nodal efficiency in the MFG and IPL partially mediated the relationship between EDS and cognitive test performance (indirect effects, -0.13 to 0.36), with mediation proportions ranging from 17% to 42%.

Clinical Context

Current OSA management centers on continuous positive airway pressure and behavioral interventions, primarily targeting respiratory events rather than downstream cognitive consequences. Glymphatic dysfunction has drawn increasing interest as a potential mechanistic link between sleep-disordered breathing and neurodegenerative risk, though its clinical utility remains investigational.

Interpretation

The authors noted that increased connectivity metrics in the MFG and IPL, both components of the default mode network, may reflect compensatory reorganization or maladaptive network strain from intermittent hypoxia and sleep fragmentation, rather than straightforward regional dysfunction. The correlation between DTI-ALPS index and apnea-hypopnea/oxygen desaturation indices supports a severity-dependent glymphatic component, though causality cannot be established from this cross-sectional design.

Limitations and Future Research

This was a single-center, cross-sectional study using one MRI scanner, limiting generalizability and precluding causal inference. Confounders such as education, smoking, depression, and anxiety were not adjusted for. Healthy controls did not undergo overnight polysomnography, relying instead on self-report and ESS screening, which may have permitted misclassification.

Nearly 25% of participants did not complete cognitive testing, and imaging proxies for glymphatic function carry known confounds, including crossing fiber effects and cerebral hemodynamic variability. The authors called for longitudinal, multicenter studies with fuller confounder adjustment and PSG-confirmed control groups to clarify whether glymphatic and network changes are reversible with treatment, and whether the MFG/IPL circuit could serve as a therapeutic target for cognitive dysfunction in OSA.

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REFERENCES
1. Li Y, Lin S, Wei H, et al. Associations Between Excessive Daytime Sleepiness, Cognitive Impairment, and Brain Alterations in Patients With Obstructive Sleep Apnea. J Magn Reson Imaging. 2026;63(6):1625-1636. doi:10.1002/jmri.70255
2. Lal C, Weaver TE, Bae CJ, Strohl KP. Excessive Daytime Sleepiness in Obstructive Sleep Apnea. Mechanisms and Clinical Management. Ann Am Thorac Soc. 2021;18(5):757-768. doi:10.1513/AnnalsATS.202006-696FR