White matter hyperintensity burden predicts cognitive but not motor decline in Parkinson's disease. Results from the ONDRI

ONDRI Investigators, 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 HaddadStephen 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, Manuel Montero-Odasso

Research output: Contribution to journalArticlepeer-review


BACKGROUND: The pathophysiology of Parkinson's disease (PD) negatively affects brain network connectivity, and in the presence of brain white matter hyperintensities (WMH) cognitive and motor impairments seem to be aggravated. However, the role of WMH in predicting accelerating symptom worsening remains controversial.

OBJECTIVE: To investigate whether location and segmental brain WMH burden at baseline predicts cognitive and motor declines in PD after 2 years.

METHODS: 98 older adults followed longitudinally from Ontario Neurodegenerative Diseases Research Initiative (ONDRI) 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 regions (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 MDS-UPDRS 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 WMH 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: WMH burden at baseline predicted only cognitive decline in PD. The motor decline observed after 2-years in these participants with early to mid-stage PD is probably related to the primary neurodegenerative process more than comorbid WM pathology.

Original languageEnglish
JournalEuropean Journal of Neurology
Early online date24 Jan 2023
Publication statusE-pub ahead of print - 24 Jan 2023


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