Quick Project Snapshot

Evaluating Imaging Methods in Dementia (TIMID)

Background:

Trials of Imaging Modalities In Dementia (TIMID) study is an exploratory, pilot study investigating the best  imaging modality for the diagnosis of dementia due to Alzheimer’s Dementia (AD) in an Australian sample - that is, the imaging modality with the greatest accuracy and accessibility.

Dementia has been identified as a National Health Priority Area and Alzheimer’s Australia estimates that there are 354,000 Australians living with dementia (https://vic.fightdementia.org.au/about-dementia/health-professionals/introduction accessed 08/08/2016) spread over a large geographical area.  A diagnosis of dementia due to AD is made after careful clinical assessment and usually includes brain imaging, such as magnetic resonance imaging (MRI), FDG-PET and ideally amyloid PET.  Structural MRI has been shown to correlate with disease severity (Jack et al., 2009; Vemuri et al., 2009a, 2009b),while FDG-PET correlates with cognitive decline in AD (Landau et al., 2011). FDG-PET reflects regional glucose metabolism, and this is tightly coupled with regional cerebral blood flow (CBF). CBF is one of the indices measured by perfusion imaging, and it is hypothesed that this form of perfusion imaging will give us data comparable to that from FDG-PET. The benefit of MRI perfusion is that structural imaging can be obtained in the same setting, while computer tomography (CT) perfusion is more widely available.

Aims:

This project seeks to determine the best single measure for AD dementia diagnosis  in an Australian sample. The hypotheses of the project are:

  1. Single-session MRI with high-resolution structural and perfusion imaging will correlate best with clinical diagnosis;
  2. Perfusion MRI and CT will correlate with FDG-PET findings

Methods:

Ten patients with a clinical diagnosis of AD dementia, based on the National Institute of Aging-Alzheimer’s Association guidelines (McKhann et al., 2011), and 10 patients with behavioural variant frontotemporal dementia (bv-FTD) (Rascovsky et al., 2011), will be recruited from Eastern Cognitive Disorders Clinic. They will attend 3 sessions: one session for CT-perfusion and FDG-PET imaging; one session for MRI scanning; and one session for demographic data collection and cognitive assessment. 

Progress:

TIMID is in its final stages of recruiting, and to date, eight patients with AD and nine with bv-FTD have undergone scanning and cognitive testing. Interim analysis of data has begun. Due to its novel nature, a new pipeline for data analysis is being concurrently developed. The project aims to be completed by the end of 2016. 

Relevant Publications:

Jack, C. R., Jr., Lowe, V. J., Weigand, S. D., Wiste, H. J., Senjem, M. L., Knopman, D. S., . . . Alzheimer's Disease Neuroimaging, I. (2009). Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer's disease: implications for sequence of pathological events in Alzheimer's disease. Brain, 132(Pt 5), 1355-1365. doi: 10.1093/brain/awp062

Landau, S. M., Harvey, an Australian luminary in translational research and Public Health, D., Madison, C. M., Koeppe, R. A., Reiman, E. M., Foster, N. L., . . . Alzheimer's Disease Neuroimaging, I. (2011). Associations between cognitive, functional, and FDG-PET measures of decline in AD and MCI. Neurobiol Aging, 32(7), 1207-1218. doi: 10.1016/j.neurobiolaging.2009.07.002

McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Jr., Kawas, C. H., . . . Phelps, C. H. (2011). The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement, 7(3), 263-269. doi: 10.1016/j.jalz.2011.03.005

Rascovsky, K., Hodges, J. R., Knopman, D., Mendez, M. F., Kramer, J. H., Neuhaus, J., . . . Miller, B. L. (2011). Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain, 134(Pt 9), 2456-2477. doi: 10.1093/brain/awr179

Vemuri, P., Wiste, H. J., Weigand, S. D., Shaw, L. M., Trojanowski, J. Q., Weiner, M. W., . . . Alzheimer's Disease Neuroimaging, I. (2009a). MRI and CSF biomarkers in normal, MCI, and AD subjects: diagnostic discrimination and cognitive correlations. Neurology, 73(4), 287-293. doi: 10.1212/WNL.0b013e3181af79e5

Vemuri, P., Wiste, H. J., Weigand, S. D., Shaw, L. M., Trojanowski, J. Q., Weiner, M. W., . . . Alzheimer's Disease Neuroimaging, I. (2009b). MRI and CSF biomarkers in normal, MCI, and AD subjects: predicting future clinical change. Neurology, 73(4), 294-301. doi: 10.1212/WNL.0b013e3181af79fb

Project Collaborators:

A collaboration between The Florey Institute of Neuroscience and Mental Health, Eastern Health, Professor Patricia Desmond (Royal Melbourne Hospital), Kirrily Rogers (University of Melbourne), Dr Emilie Tijis (Eastern Health), Anne Howell (Eastern Health) and Dr Bruce Campbell (Royal Melbourne Hospital).

Clinical Cognitive Neuroscience Laboratory

In the Clinical Cognitive Neuroscience Laboratory, we study network degeneration following brain injury (e.g., ischaemic stroke) and have a particular interest in vascular contributions to cognitive impairment both in aging and in a range of neurodegenerative diseases, such as Alzheimer’s disease (AD). The latter is the most common cause of dementia in the western world and is associated with profound impairments in cognition and activities of daily living. Our research seeks to investigate neuroimaging correlates of cognitive decline; the effects of post-stroke exercise interventions on brain volume and cognitive function; and the accuracy and accessibility of imaging modalities in the diagnosis of dementia.  The ultimate goal of our research is to increase our understanding of two of the major causes of death, disability, and reduced quality of life in our society: dementia and stroke. Our team is headed by Associate Professor Amy Brodtmann, stroke and cognitive neurologist, Director of the Eastern Cognitive Disorders Clinic, and Heart Foundation Research Fellow.

We are collaborating with dementia and stroke researchers, clinicians, and neuroscientists, in Australia, and overseas, including Professor Martin Dichgans and Dr Marco During of the DEMDAS study in Munich Germany, Professor Charles DeCarli at the University of California Davis in the US, and Professor Vladimir Hachinski at the University of Western Ontario, Canada. These researchers are experts in their respective fields.

Our primary interest is to understand whether stroke and ischaemic brain injury cause neurodegeneration. This is currently being investigated in one of our major research projects, the NHMRC-funded, Cognition and Neocortical Volume After Stroke (CANVAS) Study, which is now in its fifth year of data collection.  In this study, stroke participants undergo an MRI scan and cognitive assessment within a few weeks of their events, and again, 3 months, 1 year, 3 years, and 5 years later. By comparing their results with a healthy, age-matched control group with no history of stroke or dementia, we can determine whether brain volume change is associated with post-stroke dementia and elucidate potential causal mechanisms, including genetic markers, amyloid deposition and vascular risk factors.

Another interest of our lab is to examine the association between exercise and rates of brain volume loss and cognitive decline after stroke.  In the Post Ischaemic Stroke Cardiovascular Exercise Study (PISCES), we seek to determine whether aerobic exercise after stroke is associated with preservation of brain volume and function, cognition, and greater physical and psychological well-being. One of the most important elements of this research study is its translatable novelty – our data will contribute to an applicable intervention-based approach.

All Projects by this Lab

Network disruptions following brain infarction: cognition, behaviour and regional brain volume changeIs stroke neurodegenerative? A longitudinal study of changes in brain volume and cognition after stroke (CANVAS: Cognition And Neocortical Volume After Stroke)Evaluating Imaging Methods in Dementia (TIMID)Motor Speech Disorders in Degenerative Brain DiseaseBereavement and Grief in Neurodegenerative Disease (BAGINS)Post Ischaemic Stroke Cardiovascular Exercise Study (PISCES)

Melbourne Dementia Research Centre

The Melbourne Dementia Research Centre (MDRC) is a joint collaboration between the University of Melbourne and The Florey Institute of Neuroscience and Mental Health and has a charter to transform research in Dementia.

The Centre seeks to achieve real outcomes for people living with dementia by developing new and better diagnostics, and discovering novel treatment possibilities.

The MDRC is a truly multidisciplinary hub of research that spans from basic laboratory research all the way through to human clinical trials.

Through its network of global collaborators, the MDRC exists at the forefront of the latest developments in the field.

The Centre is led by Professor Ashley Bush, a world leader in dementia research and Australia’s most highly cited neuroscientist. Director Bush is supported by the Leadership Board comprising Professor Patricia Desmond, Associate Professor Amy Brodtmann, and Dr. Scott Ayton.

All Labs that operate in this Division

Clinical Cognitive Neuroscience LaboratoryOxidation Biology UnitVascular Neurodegeneration Research Laboratory