SLEEP SPINDLE-DURATION: A POTENTIAL BIOMARKER FOR NEURODEGENERATIVE DISORDER PHENOTYPING

Abstract Introduction Decreased sleep spindle oscillations were previously associated with cognitive decline in older adults, increased tau levels, and phenoconversion to dementia in patients with Parkinson disease (PD). We analyzed quantitative sleep spindle measures to determine if this biomarker was associated with particular neurodegenerative disorder syndromes. Methods Sleep spindle oscillations ascertained in patients broadly characterized as presumed Parkinsonian-spectrum disorders (PSD), which included the subtypes dementia with Lewy Bodies/Parkinson Disease Dementia (DLB/PDD, n=16), PD (n=16), isolated REM sleep behavior disorder (iRBD, n=19), and progressive supranuclear palsy (PSP, n=13), were compared with non-PSD subtypes Alzheimer Disease dementia (AD, n=22), mild cognitive impairment (MCI, n=35), and normal cognition (NC, n=61). Sleep Profiler studies were conducted in all participants. The automated spindle detection algorithms recognized temporal excursions in the alpha (8-12 Hz) and sigma (12-16 Hz) power of 250 milliseconds or greater, with spindle duration being the sum of all spindle elapsed times. Night-to-night variability was assessed in PSP=13, PD=16, DLB/PDD=12, AD=17, MCI=25, and NC=53. Statistical analyses included intraclass correlations (ICC) and Bland-Altman plots for two-night data, and Mann-Whitney U-tests and multiple logistic regression applied to sleep-time weight-averaged spindle-durations. Results The night-to-night spindle-duration ICC was 0.95 (P<0.0001), with a Bland-Altman bias of 0.05+/-2.83 minutes. Spindle-duration was independently associated with PSD versus non-PSD groups (P=0.017, OR 1.08, 95%-CI 1.01-1.15), but not significantly associated with age (P=0.12, OR 1.03, 95%-CI 0.99-1.07) or sex (P=0.54). When stratified by subtype, age was associated with spindle-duration when NC were compared to AD and MCI (P=0.0003, OR 1.10, 95%-CI 1.04-1.16) and when iRBD were compared to DLB/PDD, PD and PSP (P<0.05, OR 1.00, 95%-CI 0.89-1.13)Spindle-durations were reduced in PSP (0.9+/-2.1) and DLB/PDD (2.0+/-5.1) when individually compared to AD (3.2+/-7.1), iRBD (3.3+/-3.4), PD (5.3+/-6.6), MCI (5.3+/-9.7), and NC (8.0+/-11.1) subtypes (all P<0.05). AD patients also exhibited lower spindle-durations than NC (P=0.03). Conclusion Auto-detected sleep spindle-durations exhibited excellent night-to-night reliability in both NC and patients with neurologic disorders. Decreased sleep spindle-duration was independently associated with PSP and DLB/PDD, and in AD. Reduced sleep spindle duration may be a distinct sleep biomarker for those disorders likely indicating thalamocortical dysfunction. Support (If Any) NIA grants: R44AG050326, R44AG054256, P30AG62677 and R34AG56639.