Proof-of-concept for characterization of neurodegenerative disorders utilizing two non-REM sleep biomarkers

Study objective: This proof-of-concept study aimed to determine whether the combined features of two non-rapid eye movement (NREM) sleep biomarkers acquired predominantly in-home could characterize different neurodegenerative disorders. Methods: Sleep spindle duration and non-REM hypertonia (NRH) were evaluated in seven groups including a control group (CG = 61), and participants with isolated REM sleep behavior disorder (iRBD = 19), mild cognitive impairment (MCI = 41), Parkinson disease (PD = 16), Alzheimer disease dementia (ADem = 29), dementia with Lewy Bodies or Parkinson disease dementia (LBD = 19) and progressive supranuclear palsy (PSP = 13). One-way analysis of variance (ANOVA), Mann–Whitney U, intra-class (ICC) and Spearman ranked correlations, Bland–Altman plots and Kappa scores, Chi-square and Fisher exact probability test, and multiple-logistic regression were focused primarily on spindle duration and NRH and the frequencies assigned to the four normal/abnormal spindle duration/NRH combinations. Results: ANOVA identified group differences in age, sleep efficiency, REM, NRH (p < 0.0001) and sleep time (p = 0.015), Spindle duration and NRH each demonstrated good night-to-night reliabilities (ICC = 0.95 and 0.75, Kappa = 0.93 and 0.66, respectively) and together exhibited an association in the PD and LBD groups only (p < 0.01). Abnormal spindle duration was greater in records of PSP (85%) and LBD (84%) patients compared to CG, MCI, PD and ADem (p < 0.025). Abnormal NRH was greater in PSP = 92%, LBD = 79%, and iRBD = 74% compared to MCI = 32%, ADem = 17%, and CG = 16% (p < 0.005).The combination biomarker normal spindle duration/normal NRH was observed most frequently in CG (56%) and MCI (41%). ADem most frequently demonstrated normal spindle duration/normal NRH (45%) and abnormal spindle duration/normal NRH (38%). Normal spindle duration/abnormal NRH was greatest in iRBD = 47%, while abnormal spindle duration/abnormal NRH was predominant in PSP = 85% and LBD = 74%. Conclusion: The NREM sleep biomarkers spindle duration and NRH may be useful in distinguishing patients with different neurodegenerative disorders. Larger prospective cohort studies are needed to determine whether spindle duration and NRH can be combined for prodromal assessment and/or monitoring disease progression.