Beyond motor symptoms: associations between sleep disorders and multidomain functional decline in Parkinson’s disease

Sleep disorders are associated with functional outcomes in Parkinson’s disease (PD), yet their multidomain clinical correlates remain incompletely characterized. We analyzed 9195 participants from the National Alzheimer’s Coordinating Center database using inverse probability weighting (IPW) to balance measured covariates between PD patients and controls. Associations of REM sleep behavior disorder (RBD), insomnia, and sleep apnea with motor, cognitive, neuropsychiatric, and instrumental activities of daily living (IADL) outcomes were evaluated using logistic regression, exploratory sequential mediation, and machine learning.

RBD showed the broadest multidomain association profile, including stronger associations with bradykinesia, hallucinations, and selected IADL impairments. Insomnia showed a more mixed profile, with neuropsychiatric associations but inverse or null associations for several IADL items, whereas sleep apnea showed more circumscribed associations. RF models showed the strongest discrimination for RBD (AUC = 0.851) and lower discrimination for insomnia and sleep apnea (AUC = 0.667 and 0.666, respectively).

Exploratory SEM results were compatible with a motor-related indirect pathway between sleep disorders and IADL impairment (Sleep -> Motor -> IADL; statistical mediation proportion, 35.8%), whereas cognitive and neuropsychiatric pathways showed suppression patterns. Overall, distinct sleep disorders in PD were associated with different functional profiles. These findings support cautious, disorder-specific screening hypotheses that require longitudinal and interventional validation before clinical implementation.

The authors thank Maxime Usdin, Research and Development Informatics at Genentech, Inc, Derrek Hibar of Product Development at Genentech, Inc, and Suyash Mishra of Global Project Strategy at Roche Ltd, Basel, Switzerland, for their valuable feedback. The NACC database is funded by the National Institute on Aging and the National Institutes of Health Grant U24 AG072122. NACC data are contributed by the National Institute on Aging–funded ADRCs: P30 AG062429 (PI James Brewer, MD, PhD), P30 AG066468 (PI Oscar Lopez, MD), P30 AG062421 (PI Bradley Hyman, MD, PhD), P30 AG066509 (PI Thomas Grabowski, MD), P30 AG066514 (PI Mary Sano, PhD), P30 AG066530 (PI Helena Chui, MD), P30 AG066507 (PI Marilyn Albert, PhD), P30 AG066444 (PI John Morris, MD), P30 AG066518 (PI Jeffrey Kaye, MD), P30 AG066512 (PI Thomas Wisniewski, MD), P30 AG066462 (PI Scott Small, MD), P30 AG072979 (PI David Wolk, MD), P30 AG072972 (PI Charles DeCarli, MD), P30 AG072976 (PI Andrew Saykin, PsyD), P30 AG072975 (PI David Bennett, MD), P30 AG072978 (PI Neil Kowall, MD), P30 AG072977 (PI Robert Vassar, PhD), P30 AG066519 (PI Frank LaFerla, PhD), P30 AG062677 (PI Ronald Petersen, MD, PhD), P30 AG079280 (PI Eric Reiman, MD), P30 AG062422 (PI Gil Rabinovici, MD), P30 AG066511 (PI Allan Levey, MD, PhD), P30 AG072946 (PI Linda Van Eldik, PhD), P30 AG062715 (PI Sanjay Asthana, MD, FRCP), P30 AG072973 (PI Russell Swerdlow, MD), P30 AG066506 (PI Todd Golde, MD, PhD), P30 AG066508 (PI Stephen Strittmatter, MD, PhD), P30 AG066515 (PI Victor Henderson, MD, MS), P30 AG072947 (PI Suzanne Craft, PhD), P30 AG072931 (PI Henry Paulson, MD, PhD), P30 AG066546 (PI Sudha Seshadri, MD), P20 AG068024 (PI Erik Roberson, MD, PhD), P20 AG068053 (PI Justin Miller, PhD), P20 AG068077 (PI Gary Rosenberg, MD), P20 AG068082 (PI Angela Jefferson, PhD), P30 AG072958 (PI Heather Whitson, MD), and P30 AG072959 (PI James Leverenz, MD).

All funding received for this study was provided by the Guizhou Provincial Science and Technology Support Program Project (General item: 2025-117), the Key Advantageous Discipline Construction Project of Guizhou Provincial Health Commission in 2023, and the Guizhou Provincial Clinical Medical Research Center Construction Project–Neurological Disease Research (No: LCZX[2025]003). These authors contributed equally: Chao Tang, Jiaxin Yang, Ming Zhang. Department of Neurology, Guizhou Provincial People’s Hospital, Guiyang, China Chao Tang, Jiaxin Yang, Ming Zhang, Xiaoyang Lei, Yi Chen & Dian He Department of Neurology, Affiliated Hospital of Guizhou Medical University, Guiyang, China Chao Tang, Jiaxin Yang, Ming Zhang, Xiaoyang Lei, Yi Chen, Xiaoxue Peng & Dian He The authors declare no competing interests.

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