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Evaluating Imaging Methods in Dementia (TIMID)

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.

Aims

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

Single-session MRI with high-resolution structural and perfusion imaging will correlate best with clinical diagnosis;

Perfusion MRI and CT will correlate with FDG-PET findings

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.

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).

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