Could Non-REM Sleep With Hypertonia Be a Biomarker for Parkinsonian Disorders?

Non-REM hypertonia is able to distinguish patients with PSD with high sensitivity and specificity with consistent reliability.

Trends in non-rapid-eye-movement (REM) sleep with hypertonia (NRH) may be a marker for Parkinsonian spectrum disorders (PSDs), according to study findings published in Sleep Medicine.

Up to three-quarters of patients with REM sleep behavior disorder progress to dementia and among those who progress, around half develop Parkinsonism-predominant syndrome. As such, sleep characteristics may be potential early markers for neurodegenerative disease diagnosis and be able to differentiate between PSD and non-PSD.

Researchers conducted a pilot study which is part of an ongoing multicenter study focused on sleep and wake characteristics in neurodegenerative disorders. Participants with normal cognition (n=61) and neurodegenerative disorders (n=104) were recruited at 6 sites in the United States. Participants used an in-home sleep recording device (Sleep Profiler™) and an automated algorithm characterized phenotypes of interest.

The participants had mild cognitive impairment (MCI; n=35), AD (n=24), Parkinson disease (PD; n=16), dementia with Lewy bodies (DLB) or PD dementia (PDD; n=16), and progressive supranuclear palsy (PSP; n=13).

These pilot data served to describe the signal characteristics and establish face validity for NRH as a sleep biomarker for PSD-related neurodegeneration.

Compared with individuals in the neurodegenerative disorders cohorts, control individuals exhibited the following:

  • Longer sleep (mean, 7.1 vs 5.2-6.3 h)
  • Higher sleep efficiency (mean, 86.4% vs 58.4%-82.8%)
  • More time spent in N3 sleep, also known as deep sleep (mean, 21.3% vs 9.8%-18.1%)
  • More time spent in REM sleep (mean, 21.2% vs 7.5%-18.6%)
  • Longer spindle duration (mean, 7.9 vs 0.8-5.3 min)
  • Shorter sleep latency (mean, 14.9 vs 21.9-27.8 min)
  • Shorter wake after sleep onset (mean, 46.5 vs 55.6-197.1 min)
  • Fewer awakenings per hour (mean, 3.4 vs 3.7-5.1)

Abnormal NRH (≥5%) was more likely to be observed among patients with PSP (odds ratio [OR], 60.0; P <.0001), DBL/PDD (OR, 21.7; P <.0001), and PD (OR, 6.4; P <.05) compared with AD; among patients with PSP (OR, 34.7; P <.0001) and DLB/PDD (OR, 12.5; P <.001) compared with MCI; and among patients with PSP (OR, 61.2; P <.0001), DLB/PDD (OR, 22.1; P <.0001), and PD (OR, 6.6; P <.001) compared with control individuals.

The frequency of abnormal NRH was observed among 76% of the PSD groups (PD, DLB/PDD, PSP) and 19% of the non-PSD groups (control individuals, MCI, AD; P <.0001). Age, gender, and use of selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors were not predictors for abnormal NRH.

The frequency of NRH was able to differentiate between PSD from non-PSD groups with an area under the receiver operating characteristic curve of 0.78. Abnormal NRH differentiated between PSD and non-PSD groups with a sensitivity of 0.76 and specificity of 0.81.

Compared between multiple readings, the proportion of individuals with consistently normal or abnormal NRH was 87% overall. Stratified by group, the consistency was 100% in DLB/PDD, 92% in MCI, 89% in controls, 85% in PSP, 83% in AD, and 69% in PD.

This study may have been limited by using an automated sleep pattern detection algorithm.

The researchers concluded, “These pilot data served to describe the signal characteristics and establish face validity for NRH as a sleep biomarker for PSD-related neurodegeneration. NRH appeared to distinguish presumed PSD patients with high sensitivity and specificity and demonstrated consistent reliability.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Levendowski DJ, Walsh CM, Boeve BF, et al. Non-REM sleep with hypertonia in Parkinsonian spectrum disorders: a pilot investigation. Sleep Med. Published online October 4, 2022. doi:10.1016/j.sleep.2022.09.025