Non-REM sleep with hypertonia in Parkinsonian Spectrum Disorders: A pilot investigation

Daniel J. Levendowski, Christine M. Walsh, Bradley F. Boeve, Debby Tsuang, Joanne M. Hamilton, David Salat, Chris Berka, Joyce K. Lee-Iannotti, David Shprecher, Philip R. Westbrook, Gandis Mazeika, Leslie Yack, Sarah Payne, Paul C. Timm, Thomas C. Neylan, Erik K. St. Louis

Research output: Contribution to journalArticlepeer-review


Introduction: From an ongoing multicenter effort toward differentiation of Parkinsonian spectrum disorders (PSD) from other types of neurodegenerative disorders, the sleep biomarker non-rapid-eye-movement sleep with hypertonia (NRH) emerged. Methods: This study included in the PSD group patients with dementia with Lewy bodies/Parkinson disease dementia (DLB/PDD = 16), Parkinson disease (PD = 16), and progressive supranuclear palsy (PSP = 13). The non-PSD group included patients with Alzheimer disease dementia (AD = 24), mild cognitive impairment (MCI = 35), and a control group with normal cognition (CG = 61). In-home, multi-night Sleep Profiler studies were conducted in all participants. Automated algorithms detected NRH, characterized by elevated frontopolar electromyographic power. Between-group differences in NRH were evaluated using Logistic regression, Mann-Whitney U and Chi-squared tests. Results: NRH was greater in the PSD group compared to non-PSD (13.9 ± 11.0% vs. 3.1 ± 4.7%, P < 0.0001). The threshold NRH≥5% provided the optimal between-group differentiation (AUC = 0.78, P < 0.001). NRH was independently associated with the PSD group after controlling for age, sex, and SSRI/SNRI use (P < 0.0001). The frequencies of abnormal NRH by subgroup were PSP = 92%, DLB/PDD = 81%, PD = 56%, MCI = 26%, AD = 17%, and CG = 16%. The odds of abnormal NRH in each PSD subgroup ranged from 3.7 to 61.2 compared to each non-PSD subgroup. The night-to-night and test-retest intraclass correlations were excellent (0.78 and 0.84, both P < 0.0001). Conclusions: In this pilot study, NRH appeared to be a novel candidate sleep biomarker for PSD-related neurodegeneration. Future studies in larger cohorts are needed to confirm these findings, understand the etiology of NRH magnitude/duration, and determine whether it is an independent prodromal marker for specific neurodegenerative pathologies.

Original languageEnglish (US)
Pages (from-to)501-510
Number of pages10
JournalSleep Medicine
StatePublished - Dec 2022


  • Biomarker
  • Dementia
  • Neurodegeneration
  • Parkinson
  • Prodromal
  • RSWA
  • Sleep hypertonia

ASJC Scopus subject areas

  • General Medicine


Dive into the research topics of 'Non-REM sleep with hypertonia in Parkinsonian Spectrum Disorders: A pilot investigation'. Together they form a unique fingerprint.

Cite this