# Factors associated with longitudinal MDS-UPDRS III score trajectories in early-stage Parkinson’s disease

**Authors:** Wen Zhou, Duan Liu, Tian-fang Zeng, Qing-qing Xia

PMC · DOI: 10.3389/fnins.2026.1759090 · Frontiers in Neuroscience · 2026-02-20

## TL;DR

The study identifies three different motor progression patterns in early Parkinson’s disease and finds factors like baseline severity and nutritional status that predict these patterns.

## Contribution

The novel contribution is identifying distinct motor progression trajectories and their predictive factors using machine learning in early-stage Parkinson’s disease.

## Key findings

- Three motor progression trajectories were identified: slow (38%), moderate (55.9%), and rapid (6.1%).
- Higher baseline MDS-UPDRS III scores and lower serum albumin levels were strongly associated with faster progression.
- Machine learning confirmed the predictive importance of baseline severity, BMI, and striatum SBR.

## Abstract

Parkinson’s disease (PD) exhibits significant clinical heterogeneity, particularly in motor symptom progression. This study aims to identify distinct trajectories of motor progression in PD and explore associated predictive factors.

Data were obtained from the Parkinson’s Progression Markers Initiative (PPMI) database on [2025-3-25]. Motor symptom severity was measured using the MDS-UPDRS III scores. Latent class trajectory analysis was used to identify distinct progression patterns. Multinomial logistic regression and machine learning models were used to evaluate predictors.

Three distinct motor progression trajectories were identified: slow progression (38%), moderate progression (55.9%), and rapid progression (6.1%). Compared to the slow progression group, a higher baseline MDS-UPDRS III score was strongly associated with both moderate (OR = 1.27, 95% CI: 1.23–1.31, p < 0.001) and rapid progression (OR = 1.49, 95% CI: 1.43–1.57, p < 0.001). Lower serum albumin levels also significantly increased the likelihood of moderate (OR = 0.95, 95% CI: 0.91–0.99, p = 0.014) and rapid progression (OR = 0.89, 95% CI: 0.81–0.98, p = 0.016). Additionally, higher baseline BMI (per 5 kg/m2 increase) was associated with greater odds of moderate (OR = 1.19, 95% CI: 1.01–1.41, p = 0.042). Finally, each 1-unit lower mean striatum specific binding ratio (SBR) reduced the odds of moderate progression by 32% compared with the slow-progression group (OR = 0.68, 95% CI: 0.46–0.99, p = 0.044). Machine learning analysis confirmed the predictive importance of these factors, with the Random Forest model achieving an AUC of 0.950.

Baseline motor severity, dopaminergic imaging, nutritional status, and body weight are key predictors of motor progression in PD. These findings highlight the potential for early risk stratification and personalized management strategies.

## Linked entities

- **Diseases:** Parkinson’s disease (MONDO:0005180)

## Full-text entities

- **Genes:** SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, ITIH2 (inter-alpha-trypsin inhibitor heavy chain 2) [NCBI Gene 3698] {aka H2P, ITI-HC2, SHAP}, SLC6A3 (solute carrier family 6 member 3) [NCBI Gene 6531] {aka DAT, DAT1, PKDYS, PKDYS1}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}
- **Diseases:** overweight (MESH:D050177), mood disorders (MESH:D019964), obese (MESH:D009765), autonomic dysfunction (MESH:D001342), PD (MESH:D010300), inflammation (MESH:D007249), neurodegenerative disorder (MESH:D019636), Anxiety (MESH:D001007), MCI (MESH:D060825), Parkinson (MESH:D010302), adiposity (MESH:D018205), Depression (MESH:D003866), Movement Disorder (MESH:D009069), Cognitive Impairment (MESH:D003072), REM Sleep Behavior Disorder (MESH:D020187), rigidity (MESH:D009127), bradykinesia (MESH:D018476), tremor (MESH:D014202), postural instability (MESH:D054972), weight loss (MESH:D015431), toxicity (MESH:D064420)
- **Chemicals:** DaTscan (MESH:C519528), glucose (MESH:D005947)
- **Species:** Homo sapiens (human, species) [taxon 9606]

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## References

30 references — full list in the complete paper: https://tomesphere.com/paper/PMC12963062/full.md

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Source: https://tomesphere.com/paper/PMC12963062