Subcortical white matter hyperintensities and motor function in parkinson's disease: findings from the ONDRI study

Daniela Cristina Carvalho de Abreu; Frederico Pieruccini-Faria; Anthony E Lang; Benjamin Cornish; William McIlroy; Mandar Jog; Mario Masellis; Joel Ramirez; Christopher Scott; Sean Symons; Sandra E Black; Stephen R Arnott; Malcolm Binns; Derek Beaton; Brian Tan; Connie Marras; Donna Kwan; David Grimes; Robert Bartha; Manuel Montero-Odasso

doi:10.1007/s11357-025-01727-1

Subcortical white matter hyperintensities and motor function in parkinson's disease: findings from the ONDRI study

Geroscience. 2025 Jun 7. doi: 10.1007/s11357-025-01727-1. Online ahead of print.

Authors

Daniela Cristina Carvalho de Abreu^{1

2

3}, Frederico Pieruccini-Faria^{4

5}, Anthony E Lang⁶, Benjamin Cornish⁷, William McIlroy⁷, Mandar Jog⁸, Mario Masellis^{9

10}, Joel Ramirez¹⁰, Christopher Scott¹⁰, Sean Symons¹⁰, Sandra E Black¹⁰, Stephen R Arnott¹¹, Malcolm Binns¹¹, Derek Beaton¹¹, Brian Tan¹¹, Connie Marras¹², Donna Kwan¹³, David Grimes¹⁴, Robert Bartha¹⁵, Manuel Montero-Odasso¹⁶

Affiliations

¹ Department of Medicine, Division of Geriatric Medicine, Parkwood Hospital, Western University, London, Ontario, Canada. dabreu@fmrp.usp.br.
² Department of Health Science, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. dabreu@fmrp.usp.br.
³ Gait and Brain Lab, Parkwood Hospital, Rm. A-280, Western University and Lawson Health Research Institute, 801 Commissioners Rd East, London, Ontario, N6 C 5 J1, Canada. dabreu@fmrp.usp.br.
⁴ Department of Medicine, Division of Geriatric Medicine, Parkwood Hospital, Western University, London, Ontario, Canada.
⁵ Gait & Brain Lab, Lawson Health Research Institute, London, Ontario, Canada.
⁶ Edmond J Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, Division of Neurology, Department of Medicine, University of Toronto, Toronto, Canada.
⁷ Neuroscience, Mobility and Balance Lab, Department of Kinesiology and Health Sciences, University of Waterloo, Waterloo, Canada.
⁸ Division of Neurology, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
⁹ Cognitive & Movement Disorders Clinic, Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
¹⁰ L.C. Campbell Cognitive Neurology Research Unit, Hurvitz Brain Sciences Program, Sunnybrook Research Institute & Department of Medicine (Neurology), Sunnybrook HSC, University of Toronto, Toronto, Canada.
¹¹ Rotman Research Institute at Baycrest Hospital, University of Toronto, Toronto, Canada.
¹² The Edmond J Safra Program in Parkinson's disease, Toronto Western Hospital, University of Toronto, Toronto, Canada.
¹³ Centre for Neuroscience Studies, Queen's University, Kingston, Canada.
¹⁴ Department of Medicine, University of Ottawa, Brain and Mind Research Institute, Ottawa, Canada.
¹⁵ Robarts Research Institute, Department of Medical Biophysics, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada.
¹⁶ Division of Geriatric Medicine, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.

PMID: 40481924
DOI: 10.1007/s11357-025-01727-1

Abstract

Background: Motor signs, such as rigidity, bradykinesia, tremor, gait and balance impairment, are hallmark features of idiopathic Parkinson's disease (PD). The basal ganglia, involved in voluntary and automatic movements, are affected by reduced dopaminergic activity, contributing to motor signs in PD. Motor signs may be exacerbated by cortical white matter hyperintensities (WMH), but the relationship between basal ganglia WMH and motor signs remains unclear.

Objective: To investigate the association between subcortical WMH burden and motor severity in PD participants.

Method: This cross-sectional study included 140 PD participants from the Ontario Neurodegenerative Disease Research Initiative (ONDRI). The relative WMH (i.e, percentage) in the whole brain, frontal, temporal, parietal, occipital lobes, and basal ganglia+thalamus (BGT) were calculated. Adjusted regression models were used to test the associations between WMH and motor signs. WMH burden was stratified by quartiles, and Analysis of Covariance was applied to determine which WMH quartile most affected motor signs.

Results: Increased WMH burden in BGT was associated with better motor function. In contrast, WMH burden in cortical brain regions, i.e., frontal, parietal, temporal, and occipital lobes, was not associated with worse motor signs. Participants with larger BGT WMH volumes exhibited better motor function compared to those in lower quartiles CONCLUSION: Hyperintense lesions in the basal ganglia+thalamus were significantly associated with better motor function, suggesting that disruption of inhibitory basal ganglia circuitry may recalibrate motor output. These findings raise novel hypotheses about circuit-level modulation in Parkinson's disease and may guide future mechanistic and therapeutic investigations. However, as the results are correlational, they do not imply causality.

Keywords: MDS-UPDRS-III; Motor signs; Neurodegenerative disease; White matter hyperintensities.

Grants and funding

2019/24271-0/FAPESP