Alzheimer’s Research & Therapy (Jun 2023)
White matter hyperintensities and smaller cortical thickness are associated with neuropsychiatric symptoms in neurodegenerative and cerebrovascular diseases
- Miracle Ozzoude,
- Brenda Varriano,
- Derek Beaton,
- Joel Ramirez,
- Sabrina Adamo,
- Melissa F. Holmes,
- Christopher J. M. Scott,
- Fuqiang Gao,
- Kelly M. Sunderland,
- Paula McLaughlin,
- Maged Goubran,
- Donna Kwan,
- Angela Roberts,
- Robert Bartha,
- Sean Symons,
- Brian Tan,
- Richard H. Swartz,
- Agessandro Abrahao,
- Gustavo Saposnik,
- Mario Masellis,
- Anthony E. Lang,
- Connie Marras,
- Lorne Zinman,
- Christen Shoesmith,
- Michael Borrie,
- Corinne E. Fischer,
- Andrew Frank,
- Morris Freedman,
- Manuel Montero-Odasso,
- Sanjeev Kumar,
- Stephen Pasternak,
- Stephen C. Strother,
- Bruce G. Pollock,
- Tarek K. Rajji,
- Dallas Seitz,
- David F. Tang-Wai,
- John Turnbull,
- Dar Dowlatshahi,
- Ayman Hassan,
- Leanne Casaubon,
- Jennifer Mandzia,
- Demetrios Sahlas,
- David P. Breen,
- David Grimes,
- Mandar Jog,
- Thomas D. L. Steeves,
- Stephen R. Arnott,
- Sandra E. Black,
- Elizabeth Finger,
- Jennifer Rabin,
- ONDRI Investigators,
- Maria Carmela Tartaglia
Affiliations
- Miracle Ozzoude
- Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Krembil Discovery Tower
- Brenda Varriano
- Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Krembil Discovery Tower
- Derek Beaton
- Data Science & Advanced Analytic, St. Michael’s Hospital
- Joel Ramirez
- L.C. Campbell Cognitive Neurology Unit, Sunnybrook Health Sciences Centre
- Sabrina Adamo
- Graduate Department of Psychological Clinical Science, University of Toronto Scarborough
- Melissa F. Holmes
- L.C. Campbell Cognitive Neurology Unit, Sunnybrook Health Sciences Centre
- Christopher J. M. Scott
- L.C. Campbell Cognitive Neurology Unit, Sunnybrook Health Sciences Centre
- Fuqiang Gao
- L.C. Campbell Cognitive Neurology Unit, Sunnybrook Health Sciences Centre
- Kelly M. Sunderland
- Rotman Research Institute of Baycrest Centre
- Paula McLaughlin
- Nova Scotia Health
- Maged Goubran
- Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto
- Donna Kwan
- Centre for Neuroscience Studies, Queen’s University
- Angela Roberts
- Roxelyn and Richard Pepper Department of Communication Sciences and Disorders, Northwestern University
- Robert Bartha
- Robarts Research Institute, Western University
- Sean Symons
- Sunnybrook Research Institute, Sunnybrook Health Sciences Centre
- Brian Tan
- Rotman Research Institute of Baycrest Centre
- Richard H. Swartz
- Sunnybrook Research Institute, Sunnybrook Health Sciences Centre
- Agessandro Abrahao
- Sunnybrook Research Institute, Sunnybrook Health Sciences Centre
- Gustavo Saposnik
- Division of Neurology, Department of Medicine, St. Michael’s Hospital, University of Toronto
- Mario Masellis
- Sunnybrook Research Institute, Sunnybrook Health Sciences Centre
- Anthony E. Lang
- Department of Medicine, Division of Neurology, University of Toronto
- Connie Marras
- Department of Medicine, Division of Neurology, University of Toronto
- Lorne Zinman
- Sunnybrook Research Institute, Sunnybrook Health Sciences Centre
- Christen Shoesmith
- Department of Clinical Neurological Sciences, Western University
- Michael Borrie
- Robarts Research Institute, Western University
- Corinne E. Fischer
- Division of Neurology, Department of Medicine, St. Michael’s Hospital, University of Toronto
- Andrew Frank
- Department of Medicine (Neurology), University of Ottawa Brain and Mind Research Institute
- Morris Freedman
- Rotman Research Institute of Baycrest Centre
- Manuel Montero-Odasso
- Department of Clinical Neurological Sciences, Western University
- Sanjeev Kumar
- Department of Psychiatry, University of Toronto
- Stephen Pasternak
- Schulich School of Medicine and Dentistry, Western University
- Stephen C. Strother
- Rotman Research Institute of Baycrest Centre
- Bruce G. Pollock
- Department of Psychiatry, University of Toronto
- Tarek K. Rajji
- Department of Psychiatry, University of Toronto
- Dallas Seitz
- Cumming School of Medicine, University of Calgary
- David F. Tang-Wai
- Department of Medicine, Division of Neurology, University of Toronto
- John Turnbull
- Faculty of Health Sciences, McMaster University
- Dar Dowlatshahi
- Department of Medicine (Neurology), University of Ottawa Brain and Mind Research Institute
- Ayman Hassan
- Thunder Bay Regional Health Research Institute
- Leanne Casaubon
- Department of Medicine, Division of Neurology, University of Toronto
- Jennifer Mandzia
- Department of Clinical Neurological Sciences, Western University
- Demetrios Sahlas
- Faculty of Health Sciences, McMaster University
- David P. Breen
- Centre for Clinical Brain Sciences, University of Edinburgh
- David Grimes
- Department of Medicine (Neurology), University of Ottawa Brain and Mind Research Institute
- Mandar Jog
- Department of Clinical Neurological Sciences, Western University
- Thomas D. L. Steeves
- Division of Neurology, Department of Medicine, St. Michael’s Hospital, University of Toronto
- Stephen R. Arnott
- Rotman Research Institute of Baycrest Centre
- Sandra E. Black
- L.C. Campbell Cognitive Neurology Unit, Sunnybrook Health Sciences Centre
- Elizabeth Finger
- Department of Clinical Neurological Sciences, Western University
- Jennifer Rabin
- Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto
- ONDRI Investigators
- Maria Carmela Tartaglia
- Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Krembil Discovery Tower
- DOI
- https://doi.org/10.1186/s13195-023-01257-y
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 22
Abstract
Abstract Background Neuropsychiatric symptoms (NPS) are a core feature of most neurodegenerative and cerebrovascular diseases. White matter hyperintensities and brain atrophy have been implicated in NPS. We aimed to investigate the relative contribution of white matter hyperintensities and cortical thickness to NPS in participants across neurodegenerative and cerebrovascular diseases. Methods Five hundred thirteen participants with one of these conditions, i.e. Alzheimer’s Disease/Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Parkinson’s Disease, or Cerebrovascular Disease, were included in the study. NPS were assessed using the Neuropsychiatric Inventory – Questionnaire and grouped into hyperactivity, psychotic, affective, and apathy subsyndromes. White matter hyperintensities were quantified using a semi-automatic segmentation technique and FreeSurfer cortical thickness was used to measure regional grey matter loss. Results Although NPS were frequent across the five disease groups, participants with frontotemporal dementia had the highest frequency of hyperactivity, apathy, and affective subsyndromes compared to other groups, whilst psychotic subsyndrome was high in both frontotemporal dementia and Parkinson’s disease. Results from univariate and multivariate results showed that various predictors were associated with neuropsychiatric subsyndromes, especially cortical thickness in the inferior frontal, cingulate, and insula regions, sex(female), global cognition, and basal ganglia-thalamus white matter hyperintensities. Conclusions In participants with neurodegenerative and cerebrovascular diseases, our results suggest that smaller cortical thickness and white matter hyperintensity burden in several cortical-subcortical structures may contribute to the development of NPS. Further studies investigating the mechanisms that determine the progression of NPS in various neurodegenerative and cerebrovascular diseases are needed.
Keywords
- White matter hyperintensities
- Cortical thickness
- Neuropsychiatric symptoms
- Neurodegenerative disease
- Cerebrovascular disease
