ArticleFrontiers in aging neuroscience2026
Olfactory impairment and probable REM sleep behavior disorder in Parkinson's disease: clinical relevance to the single- and dual-hit hypotheses.
Article in Frontiers in aging neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Rapid eye movement (REM) sleep behavior disorder (RBD) and olfactory impairment are common prodromal features of Parkinson's disease (PD), but the implications of their coexistence remain uncertain. The dual-hit hypothesis proposes concomitant olfactory and enteric involvement, whereas the revised single-hit framework proposes predominantly brain-first or body-first routes. We examined whether probable RBD (pRBD)/anosmia-defined subgroups exhibit distinct clinical profiles. Methods: In this cross-sectional study, 201 individuals with PD underwent olfactory, cognitive, motor, non-motor, and quality-of-life assessments. Anosmia was defined as a University of Pennsylvania Smell Identification Test score <19 and pRBD as an RBD Screening Questionnaire score ≥6 supplemented by participant and informant interviews. Multivariable models evaluated the main and interactive effects of anosmia and pRBD. Results: Of 201 participants, 95 (47.3%) were pRBD-positive (pRBD+), 135 (67.2%) had anosmia, and 68 (33.8%) had both. Anosmia prevalence did not differ between the pRBD+ and pRBD-negative (pRBD-) groups (71.6% vs. 63.2%; Conclusion: In pRBD+ participants, anosmia was not associated with greater motor severity; in pRBD- participants, it was instead linked to cognitive impairment. Concurrent assessment of olfaction and pRBD may improve clinical phenotyping, but longitudinal validation is required.
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