Pathways between multiple sclerosis, sleep disorders, and cognitive function: Longitudinal findings from The Nurses' Health Study

Background: The potential mediating and moderating effects of sleep disorders on cognitive outcomes in multiple sclerosis (MS) have been insufficiently studied. Objectives: To determine direct and indirect longitudinal associations between sleep disorders and perceived cognitive dysfunction in women with MS. Methods: The 2013 and 2017 waves of the Nurses' Health Study (n = 63,866) were utilized. All diagnoses and symptoms including MS (n = 524) were self-reported. Subjective cognitive function was measured using a composite score of four memory items and three binary outcomes that assessed difficulty following instructions, conversations/plots, and street navigation. Moderating and mediating effects of diagnosed/suspected obstructive sleep apnea (OSA), sleepiness, and insomnia between MS and cognition were estimated using the four-way decomposition method. Results: Prevalence of diagnosed/suspected OSA, sleepiness, and insomnia in 2013 were higher for nurses with MS (NwMS). NwMS were more likely to report cognitive difficulties in 2017. Insomnia mediated 5.4%-15.1% of the total effect between MS and following instructions, conversations/plots, and memory impairment, while sleepiness mediated 8.6%-12.3% of the total effect for these outcomes. In interaction analyses, OSA significantly accounted for 34% of the total effect between MS and following instructions. Conclusion: Prevalent OSA, insomnia, and sleepiness could differentially moderate or mediate the effect of MS on cognition in women with MS.