Objective: To characterise one-year non-motor symptom (NMS) trajectories in Parkinson’s disease (PD) stratified by age at onset (AAO) (EOPD ≤50 years; LOPD >50 years).

Background: NMS represent a major burden in PD, yet their longitudinal trajectories by AAO are underexplored. Understanding whether EOPD vs LOPD exhibit distinct NMS phenotypes and evolution patterns could refine disease stratification and symptom monitoring strategies.

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-NMS data at baseline and 12-month follow-up were included (n=158; EOPD:n=95, LOPD:n=63). EOPD-age: 46.7±9.0years, AAO: 39.2±8.4years, disease duration: 7.4±4.5years, 70.5%male. LOPD-age: 64.1±6.6years, AAO 59.4±6.7years, disease duration 4.7±3.5years, 81.0%male. Within-group longitudinal change was assessed using Wilcoxon signed-rank test, between-group NMS severity comparisons used ANCOVA adjusted for age, sex, and disease duration. Domain prevalence (score>0) was compared using chi-square or Fisher’s exact test, and within-group prevalence change over 12 months using McNemar’s test.

Results: MDS-NMS total score remained stable over 12 months (baseline 24 (10–52)→12 months 24 (12–46), p=ns), and none of the 11 domains showed significant change in severity. At baseline, EOPD had higher prevalence of anxiety (72.6%vs54.0%, p=0.016) and impulse control disorders (18.9%vs3.2%, p=0.003), while LOPD had higher urinary NMS prevalence (49.2% vs 32.6%, p=0.034). Despite stable domain severity scores, prevalence shifted over time: apathy decreased (25.3%→17.1%, p<0.05) and cognitive NMS increased (35.4%→44.3%, p<0.05) across both phenotypes.

Conclusion: NMS severity remained stable regardless of AAO, but this aggregate stability masked domain-level change. The increase in cognitive NMS prevalence, despite a cohort with mean disease duration under eight years, suggests emerging cognitive vulnerability not captured by total burden scores. Persistent phenotype-specific differences, support trait-level distinctions rather than transient effects. Domain-specific longitudinal monitoring is therefore essential in PD, and AAO stratification reveals phenotypic variation that composite NMS scores may obscure.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/one-year-trajectories-of-non-motor-symptoms-in-parkinsons-disease-a-longitudinal-cohort-study-using-the-mds-nms-with-age-at-onset-stratification/