# The effect of levodopa on speech graphs in non-demented patients with multiple system atrophy and Parkinson’s disease

**Authors:** Jingyue Liu, Yan Zhao, Jinghong Ma, Guanyu Zhang

PMC · DOI: 10.3389/fneur.2026.1746101 · Frontiers in Neurology · 2026-02-09

## TL;DR

This study uses speech graph analysis to compare brain network differences in multiple system atrophy and Parkinson’s disease, finding that levodopa affects speech patterns in MSA-P patients.

## Contribution

The study introduces graph theory to analyze speech patterns in neurodegenerative diseases and shows how levodopa affects speech topology in MSA-P patients.

## Key findings

- MSA-P patients had denser and smaller speech graphs compared to PD patients and healthy controls.
- Levodopa doses in MSA-P patients correlated with sparser and larger speech graphs.
- Speech graph analysis can help differentiate MSA-P from PD.

## Abstract

An objective topological analysis for any arbitrary network was provided by graph theory, which was implemented to reveal topological properties of brain networks in a wide range of neurodegenerative diseases.

To investigate the difference of the topology of speech graphs among parkinsonian-type multiple system atrophy patients (MSA-P), idiopathic Parkinson’s disease (PD) patients, and healthy controls (HC). To explore the effect of levodopa on the topology of speech graphs in MSA-P and PD patients.

We applied a graph analysis of topology of speech graphs in MSA-P patients (N = 39), idiopathic PD patients (N = 51), and HC (N = 51). All participants were assessed by a well-established semantic fluency test (animal). Participants’ verbal reactions were listed and represented as speech graphs with directionality.

MSA-P patients mentioned more about their memory and remaining time than PD patients (p < 0.001) and HC (p < 0.001). Moreover, MSA-P patients’ speech graphs exhibited fewer nodes (PD: p = 0.004; HC: p < 0.001), higher density (PD: p = 0.007; HC: p < 0.001), smaller diameter (PD: p = 0.004; HC: p < 0.001), and smaller average shortest path (PD: p = 0.002; HC: p < 0.001) than both PD patients and HC. Compared with PD patients and healthy adults, the MSA-P patients generated denser and smaller speech graphs. Importantly, in MSA-P, the positive correlations between levodopa equivalent daily dose and diameter (r = 0.39, p = 0.017) and average shortest path (r = 0.38, p = 0.017) were obtained, suggesting that higher levodopa doses were associated with producing sparser and larger speech graphs in MSA-P patients. However, there was no significant correlation between levodopa equivalent daily dose and graph indices in PD patients.

MSA-P patients’ speech graphs were denser and smaller than both PD patients and healthy adults. The graph analysis of semantic fluency can differentiate MSA-P from PD to some extent. Importantly, in MSA-P patients, the impaired speech topology can be partially restored by levodopa.

## Linked entities

- **Chemicals:** levodopa (PubChem CID 6047)
- **Diseases:** multiple system atrophy (MONDO:0007803), Parkinson’s disease (MONDO:0005180)

## Full-text entities

- **Genes:** DRD1 (dopamine receptor D1) [NCBI Gene 1812] {aka D1R, DADR, DRD1A}, DRD2 (dopamine receptor D2) [NCBI Gene 1813] {aka D2DR, D2R}
- **Diseases:** HC (MESH:D000067329), MSA (MESH:D019578), brain injury (MESH:D001930), parkinsonian drugs (MESH:D010302), dementia (MESH:D003704), PD (MESH:D010300), neurodegenerative diseases (MESH:D019636), Depression (MESH:D003866), Movement Disorder (MESH:D009069), striatonigral and olivopontocerebellar degenerations (MESH:D020955), cognitive decline (MESH:D003072), inherited diseases (MESH:D030342), drug or alcohol abuse (MESH:D019966), neurological or (MESH:D009461), psychiatric disorders (MESH:D001523), AD (MESH:D000544), cerebellar (MESH:D002526), PSP (MESH:D013494)
- **Chemicals:** entacapone (MESH:C071192), amantadine (MESH:D000547), stalevo (MESH:C481098), anti (-), levodopa (MESH:D007980), rasagiline (MESH:C031967), selegiline (MESH:D012642), piribedil (MESH:D010891), pramipexole (MESH:D000077487), dopamine (MESH:D004298), benzhexol (MESH:D014282)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12926165/full.md

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12926165/full.md

## References

31 references — full list in the complete paper: https://tomesphere.com/paper/PMC12926165/full.md

---
Source: https://tomesphere.com/paper/PMC12926165