PT  - JOURNAL ARTICLE
AU  - Stuart J. McCarter
AU  - Grace M. Tabatabai
AU  - Ho-Yann Jong
AU  - David J. Sandness
AU  - Paul C. Timm
AU  - Katie L. Johnson
AU  - Allison R. McCarter
AU  - Rodolfo Savica
AU  - Prashanthi Vemuri
AU  - Mary M. Machulda
AU  - Kejal Kantarci
AU  - Michelle M. Mielke
AU  - Bradley F. Boeve
AU  - Michael H. Silber
AU  - Erik K. St. Louis
TI  - REM sleep atonia loss distinguishes synucleinopathy in older adults with cognitive impairment
AID  - 10.1212/WNL.0000000000008694
DP  - 2020 Jan 07
TA  - Neurology
PG  - e15--e29
VI  - 94
IP  - 1
4099  - http://n.neurology.org/content/94/1/e15.short
4100  - http://n.neurology.org/content/94/1/e15.full
SO  - Neurology2020 Jan 07; 94
AB  - Objective To determine whether quantitative polysomnographic REM sleep without atonia (RSWA) distinguishes between cognitive impairment phenotypes.Background Neurodegenerative cognitive impairment in older adults predominantly correlates with tauopathy or synucleinopathy. Accurate antemortem phenotypic diagnosis has important prognostic and treatment implications; additional clinical tools might distinguish between dementia syndromes.Methods We quantitatively analyzed RSWA in 61 older adults who underwent polysomnography including 46 with cognitive impairment (20 probable synucleinopathy), 26 probable non-synucleinopathy (15 probable Alzheimer disease, 11 frontotemporal lobar dementia), and 15 age- and sex-matched controls. Submentalis and anterior tibialis RSWA metrics and automated REM atonia index were calculated. Group statistical comparisons and regression were performed, and receiver operating characteristic curves determined diagnostic RSWA thresholds that best distinguished synucleinopathy phenotype.Results Submentalis—but not anterior tibialis RSWA—was greater in synucleinopathy than nonsynucleinopathy; several RSWA diagnostic thresholds distinguished synucleinopathy with excellent specificity including submentalis tonic, 5.6% (area under the curve [AUC] 0.791); submentalis any, 15.0% (AUC 0.871); submentalis phasic, 10.8% (AUC 0.863); and anterior tibialis phasic, 31.4% (AUC 0.694). In the subset of patients without dream enactment behaviors, submentalis RSWA was also greater in patients with synucleinopathy than in those without synucleinopathy. RSWA was detected more frequently by quantitative than qualitative methods (p = 0.0001).Conclusion Elevated submentalis RSWA distinguishes probable synucleinopathy from probable nonsynucleinopathy in cognitively impaired older adults, even in the absence of clinical dream enactment symptoms.Classification of evidence This study provides Class III evidence that quantitative RSWA analysis is useful for distinguishing cognitive impairment phenotypes. Further studies with pathologic confirmation of dementia diagnoses are needed to confirm the diagnostic utility of RSWA in dementia.AD=Alzheimer disease; AHI=apnea–hypopnea index; aMCI=amnestic mild cognitive impairment; AT=anterior tibialis; AUC=area under the curve; bvFTD=behavioral variant frontotemporal dementia; DEB=dream-enactment behavior; DLB=dementia with Lewy bodies; EDC=extensor digitorum communis; ESS=Epworth Sleepiness Scale; FTD=frontotemporal dementia; %ME=% of mini-epochs; naMCI=nonamnestic mild cognitive impairment; NSYN=cognitive impairment not due to synucleinopathy; OSA=obstructive sleep apnea; PLMD=periodic limb movement disorder; PLMI=Periodic Limb Movements Index; PPA=primary progressive aphasia; PPAOS=primary progressive apraxia of speech; RAI=REM atonia index; RBD=REM sleep behavior disorder; ROC=receiver operating characteristic; RSWA=REM sleep without atonia; SM=submentalis; STMS=The Kokmen Short Test of Mental Status; SYN=probable synucleinopathy