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Objectives: Sleep disturbances are increasingly recognized as adversely affecting brain health in aging. Our aim was to investigate interrelations between subjective sleep-related symptoms, obesity, cardiometabolic disorders, brain structure and cognitive decline in a population-based aging sample., Methods: Data were extracted from the UK Biobank for anthropometric and demographic information, self-reported sleep behaviours, cardiometabolic measures, structural brain magnetic resonance imaging and cognitive test scores. "Sleep-related symptoms" (SRS) were measured using four questionnaire items: loud snoring, daytime sleepiness, likelihood to nap and difficulty getting up in the morning. Associations were tested using a structural equation model (SEM), adjusted for confounders. Further, multiple regression analysis was used to test for direct relationships between SRS and specific cognitive domains., Results: Among 36,468 participants with an average age of 63.6 (SD 7.5) years and 46.7% male, we found that SRS were associated with obesity and several pre-existing cardiometabolic disturbances. In turn, cardiometabolic disorders were associated with increased white matter hyperintensities and cortical thinning, which were related to cognitive dysfunction. SRS were also directly related to several structural brain changes and to cognitive dysfunction. Regression analyses showed that SRS were directly associated with slower reaction times, and lower scores in fluid intelligence, working memory and executive function., Conclusions: Self-reported sleep-related symptoms were associated with cognitive dysfunction directly and through pre-existing cardiometabolic disorders and brain structural alterations. These findings provide evidence that symptoms of sleep disturbances, here defined primarily by hypersomnolence and snoring, are important risk factors or markers for cognitive dysfunction in an aging population., Competing Interests: Declaration of competing interest JY: Student Award from the Faculty of Medicine, McGill University; FM: Postdoctoral Fellowship from the Fonds de recherche du Quebec – Santé; AD: Unrestricted research grant from the Canadian Institutes for Health Research; EO: none; AL: research support Fondation de l’IUCPQ, Fonds de recherche en apnée du sommeil (Alphonse l’Espérance), Reseau de recherche en santé respiratoire du Quebec, consulting fee from Institut national de l'excellence en santé et en services sociaux du Québec and Jazz Pharmaceuticals; TG: none; JK: research support from CIHR, Fonds de recherche du Quebec – Santé, Multiple Sclerosis Society of Canada, Signifier Medical, consulting fees from Powell-Mansfield Inc and Esai Inc, DSMB for Bresotec Inc; MK: Research support including equipment from CIHR, Weston Brain Foundation, Fisher Paykel, Philips, Vitalaire, The Chest Foundation, Adviory Board for Biron Soins du sommeil; Honorarium for a lecture for eMedEvents; Advisory Pannel for Jazz Pharmaceuticals., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The association between obstructive sleep apnea and cognitive functioning is not yet fully understood and could be influenced by factors such as sex, age and systemic inflammation. We determined the sex- and age-specific association between obstructive sleep apnea risk and cognitive performance, and the influence of systemic inflammation on this association., Methods: We included 25,899 participants from the Canadian Longitudinal Study of Aging comprehensive cohort, aged 45-85 years (51% women). We conducted sex- and age-specific (45-59; 60-69; ≥70) general linear models between obstructive sleep apnea risk and cognitive scores, and tested the moderating and mediating effects of high-sensitivity C-reactive protein levels. Obstructive sleep apnea risk was estimated by combining the STOP and whole-body fat percentage. Cognitive tests assessed episodic verbal memory, executive functions and psychomotor speed. Levels of high-sensitivity C-reactive protein were obtained through blood samples., Results: Higher obstructive sleep apnea risk was associated with poorer episodic memory in women aged 45-59 years, and poorer executive function (p < 0.05 on multiple tests) in women aged 45-59 and 60-69 years. No such association was found in men. High-sensitivity C-reactive protein levels mediated some associations between obstructive sleep apnea risk and executive function in women and men aged <70 years., Conclusions: Being at high-risk for obstructive sleep apnea is associated with poorer cognition in women aged <70 years. These associations were partly mediated by systemic inflammation. These results underscore the importance of obstructive sleep apnea diagnosis, treatment and appropriate follow-up, particularly in middle-aged women who might already show signs of early cognitive impairments., (Copyright © 2022 Elsevier B.V. All rights reserved.)