Predicting Post-Mortem α-Synuclein Pathology by the Combined Presence of Probable REM sleep behavior disorder and Hyposmia.

Document Type

Article

Abstract

BACKGROUND: Idiopathic rapid eye movement sleep behavior disorder (RBD) is a strong known predictor of a final clinicopathological diagnosis of a Lewy type α-synucleinopathy (LTS). Olfactory dysfunction is an early symptom of synucleinopathies and has been repeatedly associated with the presence of post-mortem LTS.

OBJECTIVE: To assess the combined value of a clinician diagnosis of probable RBD (PRBD) and hyposmia in predicting the post-mortem presence of LTS in a broader, less-selected, volunteer elderly population.

METHODS: We studied 652 autopsied subjects from the Arizona Study of Aging and Neurodegenerative Disorders, which were evaluated for PRBD, had completed annual movement and cognitive assessments, and had at least one the University of Pennsylvania Smell Identification Test (UPSIT) olfactory test.

RESULTS: Histological evidence of LTS was significantly more frequent in those who had PRBD (112/152: 73.7%) than those without (177/494: 35.8%) (P < 0.001). LTS was more frequent in cases with PRBD and a low UPSIT score (90.8%) compared to cases with PRBD only (73.7%) (P < 0.001) or cases with a low UPSIT score only (69.4%) (P < 0.001). Sensitivity of PRBD diagnosis for predicting LTS was 38.8% and specificity 88.8%, whereas sensitivity of a low UPSIT score was 74.4% and specificity 73.4% (Youden's index = 0.276 for PRBD, 0.478 for UPSIT). When combining both measures, sensitivity was 34.3% and specificity increased to 97.2%.

CONCLUSION: PRBD, diagnosed without sleep study confirmation, combined with a reduced olfactory performance is highly specific for predicting post-mortem presence of LTS. The combination of both measures may provide a cost-effective means of predicting LTS in a broader community.

Medical Subject Headings

Humans; REM Sleep Behavior Disorder; Female; Male; alpha-Synuclein; Aged; Anosmia; Aged, 80 and over; Autopsy; Lewy Body Disease; Synucleinopathies

Publication Date

2-1-2025

Publication Title

Mov Disord Clin Pract

ISSN

2330-1619

Volume

12

Issue

2

First Page

157

Last Page

165

PubMed ID

39499184

Digital Object Identifier (DOI)

10.1002/mdc3.14244

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