The Mediating Effects of Sleep Disorders on Cognitive Outcomes in MS

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The longitudinal study finds prevalent obstructive sleep apnea, insomnia, and sleepiness could differentially mediate or moderate the effect of multiple sclerosis on cognition.

Findings from a study suggest the presence of obstructive sleep apnea (OSA), insomnia, and sleepiness, could mediate the effect of multiple sclerosis (MS) on cognition function in women.1

Insomnia and sleepiness mediated a small but significant proportion of the total effect between MS and cognitive outcomes, while obstructive sleep apnea had a significant interaction effect on the patient’s ability to follow instructions.

Because MS is a chronic autoimmune disease that affects the central nervous system, patients often experience various symptoms, including fatigue, pain, and cognitive impairment. Additionally, these sleep disorders, as well as excessive daytime sleepiness, are prevalent in this patient population. However, investigators noted the effect of symptoms on cognitive outcomes in MS is not well understood.

Tiffany Braley, MD, ​​Division of Multiple Sclerosis and Clinical Neuroimmunology, Department of Neurology, University of Michigan, Ann Arbor, MI, USA/Division of Sleep Medicine, Department of Neurology, University of Michigan, and a team of investigators aimed to determine the direct and indirect longitudinal associations between sleep disorders and perceived cognitive dysfunction in women with MS, using data from the Nurses' Health Study.

The Impact of Sleep Disorders on MS

In 2013, the prevalence of diagnosed or suspected obstructive sleep apnea, sleepiness, and insomnia was higher for nurses with MS when compared with nurses without MS. In 2017, those with MS were more likely to report cognitive difficulties than those without MS.

Investigators observed 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, obstructive sleep apnea significantly accounted for 34% of the total effect between MS and following instructions.

These findings emphasize the importance of considering sleep disorders in the assessment, and management of cognitive impairment in people with MS.

The Nurses' Health Study

Data for this investigation were collected from the Nurses' Health Study, a large, longitudinal cohort study of female nurses in the US. Data from the 2013 and 2017 waves were utilized, which included 63,866 participants.

All diagnoses and symptoms, including MS (n=524), were self-reported. Subjective cognitive function was measured using a composite score of 4 memory items and 3 binary outcomes that assessed difficulty following instructions, conversations/plots, and street navigation. Diagnosed or suspected obstructive sleep apnea, sleepiness, and insomnia were also self-reported.

Investigators estimated the moderating and mediating effects of these sleep disorders between MS and cognitive outcomes with a 4-way decomposition method.

Investigators stated future research should investigate the underlying mechanisms by which sleep disorders contribute to cognitive impairment in MS and the potential benefits of treating sleep disorders in improving cognitive outcomes.


  1. Braley TJ, Shieu MM, Zaheed AB, Dunietz GL. Pathways between multiple sclerosis, sleep disorders, and cognitive function: Longitudinal findings from The Nurses’ Health Study. Mult Scler. 2023;29(3):436-46.