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. 2023 Jun 20;15(1):114.
doi: 10.1186/s13195-023-01257-y.

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

Miracle Ozzoude  1   2   3   4 Brenda Varriano  1   5 Derek Beaton  6 Joel Ramirez  2   3 Sabrina Adamo  7 Melissa F Holmes  2   3 Christopher J M Scott  2   3 Fuqiang Gao  2   3 Kelly M Sunderland  8 Paula McLaughlin  9 Maged Goubran  3   10   11   12 Donna Kwan  13   14 Angela Roberts  15   16 Robert Bartha  17 Sean Symons  12 Brian Tan  8 Richard H Swartz  12   18   19 Agessandro Abrahao  12   18 Gustavo Saposnik  20   21 Mario Masellis  12   18 Anthony E Lang  18   22 Connie Marras  18   22 Lorne Zinman  12   18 Christen Shoesmith  23 Michael Borrie  17   23   24 Corinne E Fischer  20   21   25 Andrew Frank  26   27 Morris Freedman  8   18   28 Manuel Montero-Odasso  23   29   30 Sanjeev Kumar  31   32 Stephen Pasternak  24 Stephen C Strother  8   11 Bruce G Pollock  31   32 Tarek K Rajji  31   32   33 Dallas Seitz  34 David F Tang-Wai  18   35 John Turnbull  36   37 Dar Dowlatshahi  26 Ayman Hassan  38 Leanne Casaubon  18 Jennifer Mandzia  23   24   39 Demetrios Sahlas  36   37 David P Breen  40   41   42 David Grimes  26 Mandar Jog  23   24   43 Thomas D L Steeves  20 Stephen R Arnott  8 Sandra E Black  2   3   12   18   19   33 Elizabeth Finger  23   24 Jennifer Rabin  3   10   12   18   44 ONDRI InvestigatorsMaria Carmela Tartaglia  45   46   47   48
Collaborators, Affiliations

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

Miracle Ozzoude et al. Alzheimers Res Ther. .

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: Cerebrovascular disease; Cortical thickness; Neurodegenerative disease; Neuropsychiatric symptoms; White matter hyperintensities.

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Conflict of interest statement

TKR has received research support from Brain Canada, Brain and Behavior Research Foundation, BrightFocus Foundation, Canada Foundation for Innovation, Canada Research Chair, Canadian Institutes of Health Research, Centre for Aging and Brain Health Innovation, National Institutes of Health, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research and Innovation, and the Weston Brain Institute. TKR also received in-kind equipment support for an investigator-initiated study from Magstim, and in-kind research accounts from Scientific Brain Training Pro. SK has recieved research support from Brain and Behavior Foundation, National institute on Ageing, BrightFocus Foundation, Brain Canada, Canadian Institute of Health Research, Canadian Consortium on Neurodegeneration in Aging, Centre for Ageing and Brain Health Innovation, Centre for Addiction and Mental Health, and an Academic Scholars Award from the Department of Psychiatry, University of Toronto. He has also received equipment support from Soterix Medical. Other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Frequency of neuropsychiatric symptoms (NPS) in various neurodegenerative and cerebrovascular diseases. Notes: AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; CVD, cerebrovascular disease; FTD, frontotemporal disease; MCI, mild cognitive impairment; PD, Parkinson’s disease
Fig. 2
Fig. 2
Cluster bar graph showing group differences on neuropsychiatric subsyndromes. Notes: AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; CVD, cerebrovascular disease; FTD, frontotemporal disease; MCI, mild cognitive impairment; PD, Parkinson’s disease
Fig. 3
Fig. 3
Frequency of neuropsychiatric symptoms (NPS) by sex across the entire sample
Fig. 4
Fig. 4
Partial least square correlation diagram for neuropsychiatric subsyndromes component scores. Notes: the values for all subsyndromes appear in the same direction where apathy shows the highest amount of variance on Component 1
Fig. 5
Fig. 5
Partial least square correlation diagram for stable contributors component scores. Notes: the stable contributors go in the opposite direction as the neuropsychiatric subsyndromes scores, indicating a negative correlation between them. LH, left hemisphere; MoCA, Montreal Cognitive Assessment; RH, right hemisphere
Fig. 6
Fig. 6
Relationship between diagnosis, neuropsychiatric subsyndromes, and contributors. Notes: FS, FreeSurfer cortical thickness (68 regions); WMH, lobar white matter hyperintensities (10 regions); MoCA = Montreal Cognitive Assessment; AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; CVD, cerebrovascular disease; FTD, frontotemporal disease; MCI, mild cognitive impairment; PD, Parkinson’s disease

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