White matter hyperintensities and smaller cortical thickness are associated with neuropsychiatric symptoms in neurodegenerative and cerebrovascular diseases

ONDRI Investigators, 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 SaposnikMario 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, Maria Carmela Tartaglia

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)114
JournalAlzheimer's research & therapy
Issue number1
Publication statusPublished - 20 Jun 2023

Keywords / Materials (for Non-textual outputs)

  • Humans
  • Female
  • White Matter/diagnostic imaging
  • Frontotemporal Dementia
  • Parkinson Disease
  • Cognitive Dysfunction/psychology
  • Cerebrovascular Disorders/complications
  • Magnetic Resonance Imaging


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