Quick Project Snapshot
Diabetes and Dementia (D2)
Type 2 diabetes mellitus (T2DM) and dementia are two of the commonest and most disabling conditions worldwide, responsible for an enormous and growing burden of disease. There is increasing awareness that the two conditions are linked, with cognitive impairment (worsening memory, thinking, perception) common in patients with T2DM, and a strong association between T2DM and Alzheimer’s disease, the most common form of dementia.
But which patient will dement? And which biomarker will predict cognitive decline? We need better biomarkers if we want to better manage the long-term complications of diabetes. Left ventricular hypertrophy (LVH) is potentially such a marker as it is prevalent in diabetes and a strong, independent predictor of cardiovascular disease events, such as stroke and heart failure. To date there have been no studies investigating the association between LVH and cognitive decline in T2DM.
In this study we will establish whether people with T2DM and LVH have increased rates of brain atrophy and cognitive decline compared to people with T2DM but without LVH.
A single centre observational case control study that will follow 168 adult patients aged >50 years with type 2 diabetes, 50% with LVH (case) and 50% without (control). The study will intensively document the cardiovascular status of patients, perform brain imaging and neuropsychological testing between two time-points, baseline (0 months) and 2 years.
Baseline and 2 year testing includes structural neuroimaging with MRI to assess global brain volume, regional cortical thickness and hippocampal volume, an echocardiogram to assess the absence or presence of LVH, a carotid ultrasound to assess vascular disease, 24-hour ambulatory blood pressure and ECG monitoring, cognitive assessment, and APOE gene risk assessment.
The study has received ethics approval (HREC/15/Austin/490) and recruitment commenced in May 2016.
Collaboration between the Florey Institute, University of Melbourne and Austin Health
Dr Elif Ekinci, Dr Piyush Srivastava, Dr Jay Ramchand, Dr Bryan Wai Associate, Professor Brian Chambers, Associate Professor Christopher O’Callaghan & Professor Louise Burrell.
Vascular Neurodegeneration Research Laboratory
In 2016, Associate Professor Amy Brodtmann and co-investigators were awarded a Dementia Research Team Grant (DRTG). The NHMRC offered this $6.5 million grant to only a select few exceptional teams undertaking dementia research, with the aim to provide support in undertaking high quality dementia research over a five year period. The grants were designed to promote the effective collaboration of research spanning from discovery research through to clinical treatment trials.
As a clinical stroke and cognitive neurologist with a PhD in cognitive neuroscience, Associate Professor Brodtmann founded her career on merging these two areas of expertise. Her interest is exploring the mechanisms by which vascular risk factors and brain ischemia drive and determine neurodegeneration and cognitive decline All late-onset dementia syndromes, especially Alzheimer’s disease (AD), are driven or exacerbated by vascular brain burden. In this series of connected projects we ask, not whether, but how does vascular burden and injury cause dementia and neurodegeneration? With the financial support of the DRTG grant, Associate Professor Brodtmann and her team of international leaders in their fields aim to identify these mechanisms, with a view to prevent late-life cognitive decline via targeted risk management, as well as the development of treatments to prevent dementia. Dr Emilio Werden, a research neuropsychologist, is the Project Manager and oversees the operational aspects of projects conducted under the DRTG.
As CIA of the project, Associate Professor Brodtmann formed a multidisciplinary team of world-leading researchers, including Professor Charles DeCarli of University of California Davis, a world leader in vascular dementia and expert in translating research into clinical settings and public policy, Professor Vladimir Hachinski, arguably the world’s leading expert on vascular dementia, Professor John McNeil, an Australian luminary in translational research and Public Health, Professor Geoffrey Donnan, Director of The Florey institute of Neuroscience and Mental Health and a pioneer in stroke research, Professor Louise Burrell, Professor Martin Dichgans, Professor Leonid Churilov, Associate Professor David Darby, Dr Toby Cumming, Dr Marco Duering, Dr Katherine Jackman, Dr Jess Nithianantharajah, and Dr Lachlan Thompson. Working with these, and other local and international, collaborators on the project, Associate Professor Brodtmann has several studies currently in progress.
One of the keystone projects is the Cognition And Neocortical Volume After Stroke (CANVAS) Study, originally started in 2011 with funding from the Brain Foundation. The DRTG has enabled the project to continue on to five years.
In another exciting study, the Diabetes and Dementia (D2) team intensively documents the cardiovascular status of patients with T2DM. Participants are recruited with T2DM, upon which we integrate transthoracic echocardiography, neuroimaging, circulating and genetic biomarkers and neuropsychology tools to establish the relationship between T2DM and brain atrophy and cognitive decline in a cohort of 168 individuals with and without LVH. Baseline testing includes structural neuroimaging with MRI to assess global brain volume, regional cortical thickness and hippocampal volume, an echocardiogram to assess the absence or presence of LVH, a carotid ultrasound to assess vascular disease, 24-hour ambulatory blood pressure and ECG monitoring, cognitive assessment, and APOE gene risk assessment. After the baseline evaluation, a follow-up assessment will be repeated at the 24-month interval.
All Projects by this LabDiabetes and Dementia (D2)Post-Stroke Longitudinal Imaging & Behavioural Change in Rodent ModelsCognition And Neocortical Volume After Stroke (CANVAS)
The Division of Behavioural Neuroscience focuses on the use and development of models that reflect aspects of human disorders such as addiction, anxiety, depression, schizophrenia, autism and neurodegenerative conditions such as Huntington’s disease. The Cognitive Neuroscience group additionally studies cognitive disorders caused by diseases such as stroke (cerebrovascular disease), Alzheimer's disease and other dementias from a clinical perspective.