QUT & CSIRO

Detection of longitudinal brain atrophy consistent with progression towards Alzheimer’s disease

Alzheimer’s disease (AD) is the most common form of dementia world wide. Thus in many countries, including Australia, AD has been identified as a research priority. In Australia the prevalence of dementia is set to increase from 245,000 in 2009 to 1.13 million by 2050,  the minimum health and aged care costs for Australian’s with dementia was $4.9 billion in 2009-2010, and this is set to rise with the increasing aging population. Numerous environmental and lifestyle factors have been identified that are significantly associated with reduced age of onset and severity of AD dementia. However there is currently no model that combines environmental, lifestyle and biomarker (biochemical and bioimaging) factors. If such a model was developed, it would provide a better understanding of the complex relationships between different brain regions and how they degenerate over time.

The progression of AD is known to be linked to specific regions of the brain associated with memory and cognitive domains. Generally, deterioration of brain regions commence prior to the onset of cognitive decline and before clinical symptoms of AD occur. The figure below illustrates the cascading nature of biomarkers such as Beta Amyloid load, brain atrophy (measured by neuroimaging techniques), cognitive and memory decline (measured by psychological assessments).

ADmodel

The aim of this project is to develop statistical models to assess longitudinal neurodegeneration. The expected outcome of this research is the derivation of models which have the ability to incorporate expert clinical information (in form of a prior) to further enrich the model driven process, and account for substantial variability in data with a hierarchical structure. These models will be used to provide insight into the disease pathology in the pre-symptomatic phase, establishing critical spatial and/or temporal points in neurodegeneration stages where healthy atrophy and AD related atrophy diverge. This will potentially facilitate the use of preventative methods and therapeutic measures that aim to delay disease severity and onset, before clinical and cognitive symptoms have been identified. This project is a collaboration between QUT and the CSIRO. Which consists of analysing data from the Australian Imaging, Biomarkers and Lifestyle Flagship study of ageing (AIBL) study, which is the largest longitudinal neuroimaging, cognitive characteristics and health and lifestyle factors study of its kind in Australia.

Members of the research team include: Marcela Cespedes (PhD candidate), Dr James McGree (principal supervisor), Dr James Doecke (CSIRO), Dr Jurgen Fripp (CSIRO), Dr Christopher Drovandi and Professor Kerrie Mengersen (associate supervisors).

References

K. A. Ellis, A. I. Bush, D. Darby, D. De Fazio, J. Foster, P. Hudson, N. T. Lautenschlager, N. Lenzo, R. N. Martins, P. Maruff, et al. The Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging: methodology and
baseline characteristics of 1112 individuals recruited for a longitudinal study of Alzheimer’s disease. International Psychogeriatrics, 21(04):672–687, 2009.

H. Brodaty and A. Cumming. Dementia services in Australia. International Journal of Geriatric Psychiatry, 25(9):887–995, 2010.

M. W. Weiner, D. P. Veitch, P. S. Aisen, L. A. Beckett, N. J. Cairns, R. C. Green, D. Harvey, C. R. Jack, W. Jagust, E. Liu, et al. The Alzheimer’s Disease Neuroimaging Initiative: a review of papers published since its inception.
Alzheimer’s & Dementia, 9(5):e111–e194, 2013.

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