Probable REM sleep behavior disorder marks a less levodopa-responsive phenotype in Parkinson's disease

Probable REM sleep behavior disorder (pRBD) is a clinically relevant phenotype in Parkinson's disease (PD), commonly associated with greater non-motor burden and a more diffuse disease profile. However, its independent clinical correlates remain incompletely defined, particularly regarding acute dopaminergic responsiveness.

To identify independent clinical correlates of pRBD in a comprehensively phenotyped PD cohort, with particular attention to acute levodopa responsiveness.

In this retrospective cross-sectional study, 468 patients with PD underwent multidimensional motor and non-motor assessments. Probable RBD (pRBD) was determined using an informant-based screening item derived from the Mayo Sleep Questionnaire. Acute dopaminergic responsiveness was quantified using standardized OFF-ON MDS-UPDRS part III evaluations. Multivariable logistic regression was performed to identify independent correlates of pRBD. An exploratory secondary analysis examined individual NMSS subdomains.

Probable RBD was identified in 158/468 patients (33.8%). In multivariable analysis, male sex (OR 1.72, 95% CI 1.07-2.75; p = 0.024), anosmia/hyposmia (OR 2.29, 95% CI 1.47-3.55; p < 0.001), constipation (OR 1.99, 95% CI 1.23-3.24; p = 0.005), and lower total levodopa response rate (OR 0.27, 95% CI 0.08-0.93; p = 0.038) were independently associated with pRBD. Among these, lower acute levodopa responsiveness represented a clinically distinctive and robust independent association. In the exploratory analysis, only the gastrointestinal NMSS subdomain remained independently associated with pRBD.

In PD, pRBD is independently associated with constipation, anosmia/hyposmia, male sex, and lower acute levodopa responsiveness. Reduced acute levodopa responsiveness may represent an underrecognized and clinically relevant feature of the pRBD phenotype.