1012 Concordance and Test-Retest Consistency of Sleep Biomarker Based Phenotyping of Neurodegenerative Disorders

Introduction In this pilot study, the diagnostic agreement for sleep biomarker-based neurodegenerative disorder (NDD) risk probabilities was evaluated in patients with Alzheimer’s disease dementia (AD), Lewy Body disease (LBD), and isolated REM sleep behavior disorder (iRBD) and controls with a Mini-Mental State Exam scores>28. Methods Sleep biomarkers recorded with the Sleep Profiler (Advanced Brain Monitoring, Inc) were used as inputs to a 4-class machine learning algorithm trained to assign NDD risk probabilities to AD=27, LBD=19, iRBD=15 and controls (CG=58). Input variables included age, time-REM, non-REM hypertonia, autonomic-activation index, spindle-duration, atypical-N3, time-supine, sleep-efficiency, relative-theta, and theta/alpha. Records with CG output probabilities >70% were labeled Probably-normal, and from 45-70% Likely-normal with indications of a NDD added when the LBD, AD or prodromal synucleinopathy (pSYN) risks exceeded approximately 25%. Similar thresholds were used to assign Likely- or Probable- LBD, AD, or pSYN based each of the group probabilities. Classification accuracies were evaluated in AD=37, LBD=19, iRBD=19 and CG=61 records. Longitudinal test-retest reliabilities were assessed for CG (n=45, range 8-56 months), and after six-months for LBD (n=10) and AD (n=9). Results In the AD group, NDD risk assignments were consistent with diagnoses=85%, with Probable-NDD=59%, Likely-NDD=11%, Normal plus AD/Mixed indications=15%, but with 5%=Probably-normal. In the LBD group, assigned risks were consistent with the diagnosis=79%, with Probable-NDD=74%, Normal with pSYN indications=5%, but with 11%=Probably-normal. In the iRBD group, Probable-NDD=42%, Normal plus pSYN indications=26% and Probably-normal=32%. In the CG group, 89% were assigned minimal NDD risks with Probably-normal=67%, Normal plus indications=22%, but with Likely NDD=8% and Probable NDD=3%. The AD test-retest reliability showed the same NDD classifications=78%, with slightly increasing=11% and decreased=11%. In the LBD group, the same NDD classifications were achieved=80%, with trending equivalence=10%, and decreasing severity=20%. The CG test-retest reliability showed the same NDD classifications=76%, with trending equivalence=22%, and increased severity=2%. Conclusion Consistencies between the diagnoses and assigned NDD risks and test-retest classification agreements were approximately 80% in the AD, LBD, and CG groups. In the iRBD group, the NDD risks were disbursed consistent with the range of expected severities. These results needed to be cross-validated in independent NDD datasets. Support (if any) NIH grants R44AG050326, R44AG054256, RO1AG060477, R33AG064271, ULRR024150, R34AG056639.