Objective: To determine whether motor severity differences between EOPD ≤50 years and LOPD >50 years reflect age at onset (AAO)-related biology or disease duration, and to characterise one-year OFF-state motor progression in both phenotypes.

Background: Disease duration is an important driver of motor severity, yet few have adequately controlled for this variable when comparing phenotypes. Understanding whether progression rates differ independent of disease duration has implications for prognosis, treatment stratification, and the biological mechanisms underlying motor deterioration.

Method: Participants were prospectively recruited (July 2022–February 2026) as part of the YLOPD study funded by the SKAN Research Trust at NIMHANS, Bengaluru, India. Patients with complete MDS-UPDRS III OFF-state baseline data and 12-month follow-up were included(n=160;EOPD:n=94,LOPD:n=66). EOPD had mean age: 46.4±8.9 years, AAO:39.1±8.4 years, disease duration:7.3±4.6 years, 73.4% male; LOPD had mean age:64.2±6.4 years, AAO:59.4±6.7 years, disease duration:4.8±3.6 years,83.3% male. Within-group change was assessed using paired t-test or Wilcoxon signed-rank test. Between-group used ANCOVA adjusted for age, sex, and disease duration. A pre-specified duration-matched sensitivity analysis (2–8 years; EOPD n=63, LOPD n=38) repeated comparisons using design-based duration control.

Results: EOPD had higher raw baseline MDS-UPDRS-III OFF scores than LOPD (43.3±19.0 vs 34.8±18.6, p=0.003), but this difference disappeared after adjustment for age, sex, and disease duration. Disease duration correlated with motor severity (ρ=0.397, p<0.001), whereas age at assessment did not (ρ=−0.141, p=ns). Both groups worsened over 12 months: increase by +4.2 points in EOPD(p=0.003) and +7.0 points in LOPD(p<0.001), with equivalent progression after adjustment (Δ p=0.302). In the duration-matched analysis, baseline severity was comparable (40.4±17.0 vs 37.2±19.3, p=ns) and progression remained similar (+2.7 vs +5.3 points, p=ns).

Conclusion: EOPD and LOPD progress at equivalent rates over 12 months, confirmed in both adjusted and duration-matched analyses. Baseline differences therefore reflect disease duration rather than AAO biology. Once PD is established, AAO does not predict the rate of motor deterioration.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/influence-of-disease-duration-on-motor-progression-in-parkinsons-disease-a-longitudinal-cohort-study-with-age-at-onset-stratification-and-sensitivity-analysis/