Diagnostic Yield of REM Sleep Muscle Activity for Presumed Synucleinopathy Neurodegeneration (N7.001)

Objective: To determine whether polysomnographic REM sleep without atonia (RSWA) distinguishes between clinically diagnosed synucleinopathy (SYN) and non-synucleinopathy (NSYN) etiologies of cognitive impairment and/or parkinsonism. Background: Neurodegenerative disease arises more commonly secondary to two proteinopathies; alpha-synuclein [(Parkinson disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB)] and tau [(Alzheimer’s dementia (AD), frontotemporal dementia (FTD), progressive supranuclear palsy (PSP) or corticobasal syndrome (CBS)], although other proteinopathies frequently co-exist. Symptom overlap complicates accurate antemortem diagnosis and additional diagnostic tools to distinguish between clinically diagnosed SYN and NSYN etiologies are needed. Design/Methods: We analyzed quantitative RSWA in 138 patients; 73 SYN (33 PD, 20 MSA, 20 DLB), 50 NSYN (15 AD, 11 FTD, 17 PSP, 7 CBS), and 15 primary snoring controls. Phasic, tonic, and “any” muscle activity percentages and phasic burst durations were calculated in the submentalis (SM) and anterior tibialis (AT) muscles. The automated REM atonia index was also determined in SM. Statistical group comparisons and regression were performed, and receiver operating characteristic (ROC) curves used to determine RSWA cutoffs that distinguished SYN from NSYN. Results: All RSWA measures were significantly greater in SYN patients. SM cutoffs with AUC >0.9 (sensitivity, specificity) were: “any” 11.5% (75%, 96%); phasic 10.8% (75%, 98%); phasic burst duration 0.61 seconds (74%, 94%). In contrast, AT SYN discrimination was poor. Cutoffs were similar irrespective of clinical dream enactment behavior. Subgroup analysis showed greatest SM RSWA in patients with MSA, similar RSWA elevations in PD and DLB patients, and control level RSWA in AD, FTD, PSP and CBS patients. Conclusions: Quantitative submentalis REM sleep muscle activity accurately distinguished clinically diagnosed SYN from NSYN etiologies, even without clinical dream enactment. Polysomnographic RSWA appears to be a useful diagnostic tool for probable alpha-synucleinopathy in patients with parkinsonism and/or cognitive impairment. Study Supported by: This study was supported in part by a Mayo Clinic Alzheimer’s Disease Research Center Grant AG016574. Disclosure: Dr. McCarter has nothing to disclose. Dr. Feemster has nothing to disclose. Dr. Tabatabai has nothing to disclose. Dr. Sandness has nothing to disclose. Dr. Timm has nothing to disclose. Dr. McCarter has nothing to disclose. Dr. Talley has nothing to disclose. Dr. Hancock has nothing to disclose. Dr. Savica has nothing to disclose. Dr. Vemuri has nothing to disclose. Dr. Mielke has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly, Lysosomal Therapeutics, Inc. Dr. Machulda has nothing to disclose. Dr. Kantarci has nothing to disclose. Dr. Singer has nothing to disclose. Dr. Coon has nothing to disclose. Dr. Josephs has nothing to disclose. Dr. Boeve has received research support from GE Heathcare and Axovant. Dr. Silber has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with UptoDate, Oakstone Publishing. Dr. St. Louis has nothing to disclose.