Sleep-disordered breathing and neurocognitive function in multiple sclerosis: Differential associations across cognitive domains

Background: Sleep disorders are common in people with multiple sclerosis (PwMS) and could contribute to cognitive dysfunction. However, effects of pathological sleep on cognitive domains are insufficiently characterized. Objective: To evaluate associations between cognitive performance and polysomnographic (PSG)-based sleep disturbances in PwMS. Methods: PwMS with known/suspected untreated obstructive sleep apnea (OSA, N = 131) underwent PSG and cognitive tests: Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), California Verbal Learning Test-II (CVLT-II), Brief Visuospatial Memory Test-Revised (BVMT-R Total and Delayed), Judgment of Line Orientation (JLO), Controlled Oral Word Association Test (COWAT), Trail Making Test, Go/No-Go, and Nine-Hole Peg Test (NHPT). Results: Apnea severity measures were associated with worse processing speed, attention, and working memory (SDMT); immediate and delayed visual memory (BVMT-R Total and Delayed); attention, psychomotor speed, and cognitive flexibility (Trails); and manual dexterity and visuomotor coordination (NHPT) (ps ⩽ 0.011). Sleep macrostructure measures showed stronger associations with verbal memory and response inhibition (CVLT-II Total Recognition Discriminability Index), and immediate visual memory (BVMT-R Total) (ps ⩽ 0.011). Conclusions: Pathological sleep, including hypoxia, sleep fragmentation, and disturbances in sleep/wake states, are differentially associated with worse cognitive performance in PwMS. These findings could inform future personalized approaches to cognitive impairment in PwMS with sleep disorders. Trial registration: ClinicalTrials.gov identifier: NCT02544373 (https://clinicaltrials.gov/ct2/show/NCT02544373).

[1]  G. Dunietz,et al.  Pathways between multiple sclerosis, sleep disorders, and cognitive function: Longitudinal findings from The Nurses’ Health Study , 2023, Multiple sclerosis.

[2]  R. Chervin,et al.  The association between obstructive sleep apnea risk and cognitive disorders: a population-based study. , 2021, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[3]  A. Kratz,et al.  A multidimensional approach to sleep health in multiple sclerosis. , 2021, Multiple sclerosis and related disorders.

[4]  R. Chervin,et al.  Validation of an obstructive sleep apnea symptom inventory in persons with multiple sclerosis , 2021, Multiple sclerosis.

[5]  R. Chervin,et al.  Obstructive Sleep Apnea Treatment and Dementia Risk in Older Adults. , 2021, Sleep.

[6]  R. Milner,et al.  Hypoxia in multiple sclerosis; is it the chicken or the egg? , 2020, Brain : a journal of neurology.

[7]  M. Hutchinson,et al.  Impact of obstructive sleep apnoea on cognitive function in multiple sclerosis: A longitudinal study , 2020, Journal of sleep research.

[8]  J. DeLuca,et al.  Treatment and management of cognitive dysfunction in patients with multiple sclerosis , 2020, Nature Reviews Neurology.

[9]  K. Kam,et al.  Role of normal sleep and sleep apnea in human memory processing , 2018, Nature and science of sleep.

[10]  R. Chervin,et al.  Sleep and Cognitive Function in Multiple Sclerosis. , 2016, Sleep.

[11]  C. Kushida,et al.  A review of neurocognitive function and obstructive sleep apnea with or without daytime sleepiness. , 2016, Sleep medicine.

[12]  S. Ancoli-Israel,et al.  Associations Between Sleep‐Disordered Breathing, Nocturnal Hypoxemia, and Subsequent Cognitive Decline in Older Community‐Dwelling Men: The Osteoporotic Fractures in Men Sleep Study , 2015, Journal of the American Geriatrics Society.

[13]  Davide Cattaneo,et al.  Unilateral and bilateral upper limb dysfunction at body functions, activity and participation levels in people with multiple sclerosis , 2015, Multiple sclerosis.

[14]  Hirofumi Ochi,et al.  [Cognitive impairment in multiple sclerosis]. , 2014, Brain and nerve = Shinkei kenkyu no shinpo.

[15]  R. Chervin,et al.  Obstructive sleep apnea and fatigue in patients with multiple sclerosis. , 2014, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[16]  C. Filley,et al.  The Nature of Verbal Memory Impairment in Multiple Sclerosis: A List-Learning and Meta-analytic Study , 2013, Journal of the International Neuropsychological Society.

[17]  R. Bucks,et al.  Executive dysfunction in OSA before and after treatment: a meta-analysis. , 2013, Sleep.

[18]  R. Bucks,et al.  Memory and obstructive sleep apnea: a meta-analysis. , 2013, Sleep.

[19]  R. Bucks,et al.  Neurocognitive function in obstructive sleep apnoea: A meta‐review , 2013, Respirology.

[20]  L. von Koch,et al.  The relationship between walking, manual dexterity, cognition and activity/participation in persons with multiple sclerosis , 2012, Multiple sclerosis.

[21]  R. Benedict,et al.  Predicting loss of employment over three years in multiple sclerosis: clinically meaningful cognitive decline , 2010, The Clinical neuropsychologist.

[22]  J. DeLuca,et al.  The relationship between cognitive deficits and everyday functional activities in multiple sclerosis. , 2008, Neuropsychology.

[23]  Colin M. Shapiro,et al.  STOP Questionnaire: A Tool to Screen Patients for Obstructive Sleep Apnea , 2008, Anesthesiology.

[24]  M. Zimmerman,et al.  A review of neuroimaging in obstructive sleep apnea. , 2006, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[25]  Emilio Portaccio,et al.  Multiple sclerosis-related cognitive changes: A review of cross-sectional and longitudinal studies , 2006, Journal of the Neurological Sciences.

[26]  Julián Benito-León,et al.  Quality of life and its assessment in multiple sclerosis: integrating physical and psychological components of wellbeing , 2005, The Lancet Neurology.

[27]  R. Chervin Epworth sleepiness scale? , 2003, Sleep medicine.

[28]  R. Spitzer,et al.  The PHQ-9: A new depression diagnostic and severity measure , 2002 .

[29]  Ralph H B Benedict,et al.  Minimal Neuropsychological Assessment of MS Patients: A Consensus Approach , 2002, The Clinical neuropsychologist.

[30]  G. Kraft,et al.  Self-administered Expanded Disability Status Scale with functional system scores correlates well with a physician-administered test , 2001, Multiple sclerosis.

[31]  D. Greenblatt,et al.  The International Classification of Sleep Disorders , 1992 .

[32]  M. Johns,et al.  A new method for measuring daytime sleepiness: the Epworth sleepiness scale. , 1991, Sleep.

[33]  Stephen M. Rao,et al.  Cognitive dysfunction in multiple sclerosis. , 1991, Neurology.

[34]  N. Silberberg,et al.  Hand strength and dexterity. , 1971, The American journal of occupational therapy : official publication of the American Occupational Therapy Association.

[35]  S. Billinger,et al.  Individuals with mild MS with poor sleep quality have impaired visuospatial memory and lower perceived functional abilities. , 2018, Disability and health journal.

[36]  Daniel J Buysse,et al.  Which Sleep Health Characteristics Predict All-Cause Mortality in Older Men? An Application of Flexible Multivariable Approaches , 2018, Sleep.

[37]  A. Spanevello,et al.  Systemic and airway inflammation in sleep apnea and obesity: the role of ICAM-1 and IL-8. , 2010, Translational research : the journal of laboratory and clinical medicine.

[38]  S. Redline,et al.  Neuropsychological function in mild sleep-disordered breathing. , 1997, Sleep.

[39]  F. Donders On the speed of mental processes. , 1969, Acta psychologica.