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Charting cognitive and volumetric trajectories after stroke: protocol for the Cognition And Neocortical Volume After Stroke (CANVAS) study

Authors

  • Amy Brodtmann,

    Corresponding author
    1. The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Vic., Australia
    2. Austin Health, Heidelberg, Melbourne, Vic., Australia
    3. Eastern Clinical Research Unit, Monash University, Box Hill Hospital, Melbourne, Vic., Australia
    • Correspondence: Amy Brodtmann*, Melbourne Brain Centre, 245 Burgundy Street, Heidelberg, Vic. 3084, Australia.

      E-mail: agbrod@unimelb.edu.au

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  • Emilio Werden,

    1. The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Vic., Australia
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  • Heath Pardoe,

    1. The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Vic., Australia
    2. Comprehensive Epilepsy Center, Department of Neurology, New York University Langone Medical Center, New York, NY, USA
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  • Qi Li,

    1. The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Vic., Australia
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  • Graeme Jackson,

    1. The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Vic., Australia
    2. Austin Health, Heidelberg, Melbourne, Vic., Australia
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  • Geoffrey Donnan,

    1. The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Vic., Australia
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  • Tiffany Cowie,

    1. The Centre for Translational Pathology, University of Melbourne, Melbourne, Vic., Australia
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  • Jennifer Bradshaw,

    1. Austin Health, Heidelberg, Melbourne, Vic., Australia
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  • David Darby,

    1. The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Vic., Australia
    2. Melbourne Brain Centre, Royal Melbourne Hospital, Melbourne, Vic., Australia
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  • Toby Cumming

    1. The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Vic., Australia
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  • Conflict of interest: G. D. is the editor of the International Journal of Stroke. A. B. is co-section editor, Cognitive Disorders for the International Journal of Stroke.
  • Funding: This project is funded by NHMRC project grant APP1020526, and has been supported by seed funding from the Brain Foundation, J.O. and J.R. Wicking Trust, Collie Trust, and Sidney and Fiona Myer Family Foundation.

Abstract

Rationale

Globally, stroke and dementia are leading causes of disability and mortality. More than one third of stroke patients will develop dementia, but mechanisms are unclear.

Aims

The study aims to establish whether brain volume change is associated with poststroke dementia, and to elucidate potential causal mechanisms, including genetic markers, amyloid deposition and vascular risk factors. An understanding of whether – and in whom – stroke is neurodegenerative is critical for the strategic use of potential disease-modifying therapies.

Hypotheses

That stroke patients will exhibit greater brain volume loss than comparable cohorts of stroke-free controls; and that those who develop dementia will exhibit greater brain volume loss than those who do not.

Design

Advanced brain imaging techniques are used to longitudinally measure brain volume and cortical thickness in 135 stroke patients. Concurrent neuropsychological testing will correlate clinical profile with these measures.

Primary outcomes

Primary imaging end-point is brain volume change between three-months and three-years poststroke; primary clinical outcome is the presence of dementia at three-years.

Secondary outcomes

We will examine the correlations with the following variables: dementia subtype; physical activity levels; behavioral dysfunction as measured by patient and caregiver-reported scales; structural and functional brain connectivity disruption; apolipoprotein E; and specific neuropsychological test scores.

Discussion

Magnetic resonance imaging markers of structural brain aging and performance on neuropsychological tests are powerful predictors of dementia. We need to understand the trajectory of regional brain volume change and cognitive decline in patients after stroke. This will allow future risk stratification for prognostic counseling, service planning, and early therapeutic intervention.

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