Abstract / Summary
Parkinson’s disease (PD) is clinically heterogeneous, yet whether the mild motor-predominant, intermediate, and diffuse malignant (MMP/IM/DM) subtypes show objective neuromuscular and kinematic phenotypic differences remains unclear. We studied 120 patients with PD (55 men and 65 women) in the medication ON state. Subtypes were assigned using motor, cognitive, rapid eye movement sleep behavior disorder, and autonomic domains. Synchronized surface electromyography and inertial recordings were obtained from the more affected upper limb during three tremor and three movement tasks. Digital motor features were compared across subtypes using covariate-adjusted linear mixed-effects models with false discovery rate (FDR) correction. Subject-level associations with DM membership were examined using Firth penalized logistic regression with LASSO-based feature selection. Of 120 patients, 54 were classified as MMP, 46 as IM, and 20 as DM. Clinical burden showed a graded pattern, with the greatest motor and non-motor impairment in DM. Among all digital motor domains, only amplitude/speed remained significant after FDR correction ( p = 0.006). Greater amplitude/speed impairment was associated with DM versus non-DM membership in the Firth logistic regression (OR 2.902, 95% CI 1.201–10.186) and in the subsequent LASSO-selected Firth model (OR 4.444, 95% CI 1.879–13.986). Lower tremor amplitude also independently distinguished DM from non-DM (OR 0.019, 95% CI < 0.001–0.327). MMP/IM/DM subtypes exhibit measurable EMG/IMU phenotypic differences beyond conventional clinical evaluation. The amplitude/speed domain may represent a candidate digital marker for the DM phenotype, outperforming tremor and other motor domains. Longitudinal and multimodal studies are warranted to validate its prognostic and mechanistic significance.