| Title: |
Alzheimer's Biomarkers and Visuospatial Cognition in Parkinson's Disease: Modification by α-Synuclein and Mediation of Age Effects |
| Authors: |
Ledingham D; Sathyanarayana S; Stewart CB; Iredale R; Foster V; Galley D; Lad M; Baker MR; Pavese N |
| Source: |
Movement Disorders Clinical Practice, 2026 |
| Publisher Information: |
John Wiley and Sons Inc |
| Publication Year: |
2026 |
| Collection: |
Newcastle University Library ePrints Service |
| Description: |
© 2026 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Background: Visuospatial deficits in Parkinson's disease (PD) often precede dementia and complicate daily functioning. Alzheimer's disease (AD) pathology and α-synuclein aggregation frequently co-occur in PD, but their combined impact on cognition is unclear. Objectives: To examine whether AD biomarker burden relates to visuospatial performance in PD, whether this effect differs by α-synuclein status, and whether AD biomarkers mediate age-related decline. Methods: We analyzed 416 participants from the Parkinson's Progression Markers Initiative. AD biomarker burden was indexed by the cerebrospinal fluid pTau181/Aβ42 ratio; α-synuclein aggregation was assessed using seed amplification assay. Models adjusted for age, sex, education, and motor severity. Sensitivity analyses included genetic stratification and subgroup exclusion. Results: Higher AD biomarker burden was associated with poorer visuospatial performance and delayed recall. In participants with concurrent biomarker data (n = 246), AD burden interacted with α-synuclein status to predict worse visuospatial outcomes, with the greatest impairment observed in individual's positive for both biomarkers. Mediation analysis indicated that AD biomarker burden accounts for approximately 10–14% of the age effect on visuospatial performance. Conclusions: AD and α-synuclein biomarkers show associations consistent with synergistic effects on visuospatial cognition in PD. These findings are exploratory and require replication in pre-specified independent cohorts. However, if validated, testing both biomarkers could help identify individuals at higher risk of early visuospatial decline and inform hypothesis-driven stratification in future clinical trials. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
https://eprints.ncl.ac.uk/310963 |
| Availability: |
https://eprints.ncl.ac.uk/310963 |
| Accession Number: |
edsbas.6FC4D9C3 |
| Database: |
BASE |