White matter hyperintensity burden predicts cognitive but not motor decline in Parkinson's disease: results from the Ontario Neurodegenerative Diseases Research Initiative

Daniela Cristina Carvalho de Abreu; Frederico Pieruccini-Faria; Yanina Sarquis-Adamson; Alanna Black; Julia Fraser; Karen Van Ooteghem; Benjamin Cornish; David Grimes; Mandar Jog; Mario Masellis; Thomas Steeves; Nuwan Nanayakkara; Joel Ramirez; Christopher Scott; Melissa Holmes; Miracle Ozzoude; Courtney Berezuk; Sean Symons; Seyyed Mohammad Hassan Haddad; Stephen R Arnott; Malcolm Binns; Stephen Strother; Derek Beaton; Kelly Sunderland; Athena Theyers; Brian Tan; Mojdeh Zamyadi; Brian Levine; Joseph B Orange; Angela C Roberts; Wendy Lou; Sujeevini Sujanthan; David P Breen; Connie Marras; Donna Kwan; Sabrina Adamo; Alicia Peltsch; Angela K Troyer; Sandra E Black; Paula M McLaughlin; Anthony E Lang; William McIlroy; Robert Bartha; ONDRI Investigators; Manuel Montero-Odasso

doi:10.1111/ene.15692

White matter hyperintensity burden predicts cognitive but not motor decline in Parkinson's disease: results from the Ontario Neurodegenerative Diseases Research Initiative

Eur J Neurol. 2023 Apr;30(4):920-933. doi: 10.1111/ene.15692. Epub 2023 Feb 14.

Authors

Daniela Cristina Carvalho de Abreu^{1

2}, Frederico Pieruccini-Faria^{1

3}, Yanina Sarquis-Adamson³, Alanna Black³, Julia Fraser⁴, Karen Van Ooteghem⁴, Benjamin Cornish⁴, David Grimes⁵, Mandar Jog⁶, Mario Masellis^{7

8}, Thomas Steeves⁹, Nuwan Nanayakkara¹⁰, Joel Ramirez⁸, Christopher Scott⁸, Melissa Holmes⁸, Miracle Ozzoude⁸, Courtney Berezuk⁸, Sean Symons⁸, Seyyed Mohammad Hassan Haddad¹⁰, Stephen R Arnott¹¹, Malcolm Binns¹¹, Stephen Strother¹¹, Derek Beaton¹¹, Kelly Sunderland¹¹, Athena Theyers¹¹, Brian Tan¹¹, Mojdeh Zamyadi¹¹, Brian Levine¹¹, Joseph B Orange¹², Angela C Roberts^{12

13}, Wendy Lou¹⁴, Sujeevini Sujanthan¹⁵, David P Breen^{16

17

18}, Connie Marras¹⁹, Donna Kwan²⁰, Sabrina Adamo²¹, Alicia Peltsch²², Angela K Troyer²³, Sandra E Black⁸, Paula M McLaughlin²⁴, Anthony E Lang²⁵, William McIlroy⁴, Robert Bartha²⁶; ONDRI Investigators; Manuel Montero-Odasso^{1

3

27}

Affiliations

¹ Gait and Brain Lab, Division of Geriatric Medicine, and Lawson Health Research Institute, Parkwood Institute, University of Western Ontario, Ontario, London, Canada.
² Department of Physical Therapy, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
³ Gait and Brain Laboratory, Lawson Health Research Institute, London, Ontario, Canada.
⁴ Neuroscience, Mobility and Balance Laboratory, Department of Kinesiology and Health Sciences, University of Waterloo, Waterloo, Ontario, Canada.
⁵ Department of Medicine (Neurology), Ottawa Hospital Research Institute, University of Ottawa Brain and Mind Research Institute, Ottawa, Ontario, Canada.
⁶ Division of Neurology, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
⁷ Cognitive and Movement Disorders Clinic, Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
⁸ L.C. Campbell Cognitive Neurology Research Unit, Hurvitz Brain Sciences Program, Department of Medicine (Neurology), Sunnybrook Research Institute, Sunnybrook HSC, University of Toronto, Toronto, Ontario, Canada.
⁹ Division of Neurology, Department of Medicine, St Michael's Hospital and University of Toronto, Toronto, Ontario, Canada.
¹⁰ Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
¹¹ Rotman Research Institute at Baycrest Hospital University of Toronto, Toronto, Ontario, Canada.
¹² School of Communication Sciences and Disorders, Faculty of Health Sciences, Canadian Centre for Activity and Aging, Western University, London, Ontario, Canada.
¹³ Department of Computer Science, Western University, London, Ontario, Canada.
¹⁴ Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
¹⁵ Department of Ophthalmology and Visual Sciences, Research Institute of the McGill University Health Center, Montreal, Quebec, Canada.
¹⁶ Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
¹⁷ Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, UK.
¹⁸ Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
¹⁹ Edmond J Safra Program in Parkinson's Disease, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
²⁰ Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada.
²¹ Graduate Department of Psychological Clinical Science, University of Toronto Scarborough, Toronto, Ontario, Canada.
²² Faculty of Engineering and Applied Science, Queen's University, Kingston, Ontario, Canada.
²³ Neuropsychology and Cognitive Health Program, Baycrest Health Sciences, Department of Psychology, University of Toronto, Toronto, Ontario, Canada.
²⁴ Nova Scotia Health, Halifax, Nova Scotia,, Canada.
²⁵ Division of Neurology, Department of Medicine, Edmond J Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
²⁶ Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Robarts Research Institute, Western University, London, Canada.
²⁷ Division of Geriatric Medicine, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.

PMID: 36692250
DOI: 10.1111/ene.15692

Abstract

Background and purpose: The pathophysiology of Parkinson's disease (PD) negatively affects brain network connectivity, and in the presence of brain white matter hyperintensities (WMHs) cognitive and motor impairments seem to be aggravated. However, the role of WMHs in predicting accelerating symptom worsening remains controversial. The objective was to investigate whether location and segmental brain WMH burden at baseline predict cognitive and motor declines in PD after 2 years.

Methods: Ninety-eight older adults followed longitudinally from Ontario Neurodegenerative Diseases Research Initiative with PD of 3-8 years in duration were included. Percentages of WMH volumes at baseline were calculated by location (deep and periventricular) and by brain region (frontal, temporal, parietal, occipital lobes and basal ganglia + thalamus). Cognitive and motor changes were assessed from baseline to 2-year follow-up. Specifically, global cognition, attention, executive function, memory, visuospatial abilities and language were assessed as were motor symptoms evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III, spatial-temporal gait variables, Freezing of Gait Questionnaire and Activities Specific Balance Confidence Scale.

Results: Regression analysis adjusted for potential confounders showed that total and periventricular WMHs at baseline predicted decline in global cognition (p < 0.05). Also, total WMH burden predicted the decline of executive function (p < 0.05). Occipital WMH volumes also predicted decline in global cognition, visuomotor attention and visuospatial memory declines (p < 0.05). WMH volumes at baseline did not predict motor decline.

Conclusion: White matter hyperintensity burden at baseline predicted cognitive but not motor decline in early to mid-stage PD. The motor decline observed after 2 years in these older adults with PD is probably related to the primary neurodegenerative process than comorbid white matter pathology.

Keywords: MDS-UPDRS-III; balance confidence; brain regions; deep white matter hyperintensities; periventricular white matter hyperintensities.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Cognition / physiology
Cognitive Dysfunction* / pathology
Gait Disorders, Neurologic*
Humans
Magnetic Resonance Imaging / methods
Neurodegenerative Diseases* / pathology
Ontario
Parkinson Disease*
White Matter* / pathology