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Is stroke neurodegenerative? A longitudinal study of changes in brain volume and cognition after stroke (CANVAS: Cognition And Neocortical Volume After Stroke)

Stroke and dementia are responsible for an enormous and growing burden of disease.

Aims

To determine whether stroke patients have reductions in brain volume in the first five years post-stroke compared to control participants

To determine whether regional and global brain volume change is associated with post-stroke dementia.

In Australia, the prevalence of dementia is projected to increase more than four-fold in the next four decades, from 245,400 people in 2009 to 1.13 million people by 2050. Stroke also has considerable burden of disease: annually 15 million people worldwide suffer a stroke, leaving 5 million disabled. Five million stroke sufferers do not survive their events.

Stroke and dementia are linked. Up to two thirds of people who have a stroke experience cognitive impairment, and more than one third will develop dementia over the subsequent five years. Moreover, risk factors for stroke and dementia are similar. Yet we still know very little about whether brain volume loss – a hallmark of dementia – occurs after stroke, and whether such atrophy is related to cognitive decline. An understanding of whether stroke is neurodegenerative, and in which patients, may be used to help guide the early delivery of disease-modifying therapies.

Methods:

CANVAS is an observational, longitudinal, case control study that is following 135 ischaemic stroke patients and 40 age-matched, healthy controls, over five years. Participants are recruited from three sites in Melbourne (Austin Health, Eastern Health, Melbourne Health), with all sessions held at The Florey, Melbourne Brain Centre, Austin Hospital campus.

Participants complete an interview, MRI scan and neuropsychological assessment at five time-points (baseline, three months, one year, three years, and five years). They also provide a blood sample to determine their genetic risk for Alzheimer’s disease. After their review sessions, participants wear an activity monitor for seven days, so we can collect information about their physical activity levels and sleep patterns.  Forty stroke participants will be invited to undergo a Positron Emission Tomography (PET) scan at their three year review session. The scan will allow us to quantify levels of a protein, called beta-amyloid, in their brains. This protein is associated with Alzheimer’s disease.

These methods allow us track changes in participants’ brain volumes and thinking skills over time and elucidate potential causal mechanisms (e.g., genetic markers, amyloid deposition, and vascular risk factors).

Progress:

The study has received ethics approval from Austin Health (H2012-04650), Eastern Health (E22-1213) and Melbourne Health (2012.164).

Recruitment for the CANVAS study ended in the mid-2015. As of August 2016, all participants had completed their one year review sessions and 53 (40 stroke) participants had completed their three year review sessions. By the end of 2016, we anticipate that seven stroke participants will have completed their five year review sessions.  The data collection phase of the study will end in mid-2020.

Research support:

CANVAS began as a pilot study in 2011 with funding from the Brain Foundation. We received additional support from the Wicking Trust, Collie Trust, and Sidney and Fiona Myer Family Foundation. 

With the receipt of an NHMRC grant in 2012 (APP: 1020526), we were able to increase the sample size to 135 stroke participants; extend the study to three years post-stroke; and include a healthy control group.

In September 2015, Associate Professor Brodtmann received one of six NHMRC-funded, Dementia Research Team Grants (APP: 1094974). This has allowed us to extend the study to five years post-stroke.

The CANVAS team greatly appreciates the financial support of the aforementioned organisations, of course, the ongoing assistance of participants in the CANVAS study and their family members. It is only with this support that the study is possible.

Publications:

Cumming, T. & Brodtmann, A. (2011). Can stroke cause neurodegenerative dementia? International Journal of Stroke, 6, 416-424.

Brodtmann, A., Werden, E., Pardoe, H., Li, Q., Jackson, G., Cowie, T., Bradshaw, J., Darby, D., & Cumming, T. (2014). Charting cognitive and volumetric trajectories after stroke: protocol for the Cognition And Neocortical Volume After Stroke (CANVAS) study. International Journal of Stroke, 9, 824-828.

Li, Q., Pardoe, H., Lichter, R., Werden, E., Raffelt, A. Cumming, T., & Brodtmann, A. (2015). Cortical thickness estimation in longitudinal stroke studies: a comparison of 3 measurement methods. NeuroImage: Clinical, 8, 526-535.

Veldsman, M., Churilov, L., Werden, E., Li, Q., Cumming, T., & Brodtmann, A., Physical activity after stroke is associated with increased inter-hemispheric connectivity of the dorsal attention network. Neurorehabilitation and Neural Repair (accepted).

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