Frontiers in aging neuroscience · 2026
Olfactory impairment and probable REM sleep behavior disorder in Parkinson's disease: clinical relevance to the single- and dual-hit hypotheses.
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Lin Chia-Yen, Chang Ting-Hsin, Lin Ling-Yu, Chang Ming-Hong
Аннотация
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%; p = 0.208). After adjustment for age, sex, and disease duration, pR+A+ and pR+A- (subgroups defined by probable RBD status [pR+/pR-] and anosmia status [A+/A-]) did not differ in any assessed outcome. The anosmia-by-pRBD interaction was negative for MDS-UPDRS part III (β = -8.3, 95% CI -15.2 to -1.4; p = 0.019). Within the pRBD- subgroup, pR-A+ participants had lower MoCA scores than pR-A- participants (β = -2.6; 95% CI -4.1 to -1.0; p = 0.001), and the anosmia-by-pRBD interaction was positive for MoCA (β = 2.3, 95% CI 0.0 to 4.5; p = 0.049). Anosmia was associated with cognitive impairment in pRBD- participants (OR 2.53, 95% CI 1.00-6.37; p = 0.049), but not in pRBD+ participants (OR 1.65, 95% CI 0.60-4.50; p = 0.331).
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.
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%; p = 0.208). After adjustment for age, sex, and disease duration, pR+A+ and pR+A- (subgroups defined by probable RBD status [pR+/pR-] and anosmia status [A+/A-]) did not differ in any assessed outcome. The anosmia-by-pRBD interaction was negative for MDS-UPDRS part III (β = -8.3, 95% CI -15.2 to -1.4; p = 0.019). Within the pRBD- subgroup, pR-A+ participants had lower MoCA scores than pR-A- participants (β = -2.6; 95% CI -4.1 to -1.0; p = 0.001), and the anosmia-by-pRBD interaction was positive for MoCA (β = 2.3, 95% CI 0.0 to 4.5; p = 0.049). Anosmia was associated with cognitive impairment in pRBD- participants (OR 2.53, 95% CI 1.00-6.37; p = 0.049), but not in pRBD+ participants (OR 1.65, 95% CI 0.60-4.50; p = 0.331).
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.