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Member Spotlight: Ramón Landin-Romero

Most people typically associate Alzheimer's disease, the most common form of dementia, with memory loss in older people. However, in reality, up to 30% of Alzheimer's disease cases present with non-memory symptoms including language, visual and/or disturbances of executive functions. This atypical form of the disease is particularly insidious as it often occurs in people under the age of 65. The younger age of onset, compounded with the variability of symptoms, leads to both frequent misdiagnosis and delayed diagnosis.

In some cases, the first symptoms emerge when a person is in their late 40's and 50's, ages at which doctors are not accustomed to seeing dementia. This early age of onset also has a far-reaching social and economic impact. Affected individuals are often a key part of a social network, may be at the peak of their careers and have dependent children. Developing dementia at such a young age leads to loss of income and serious financial hardship as well as emotional distress to partners and children. Sadly, many aspects of atypical Alzheimer's disease, such as why some people develop the disease and what determines how the disease progresses, are still not well understood.

However, there is new hope thanks to a generous donation from Otto and Judy Appenzeller to the University of Sydney for research into the causes, treatment and prevention of Alzheimer's disease.Ramon

Dr Ramón Landin-Romero is the recipient of the inaugural Appenzeller Neuroscience Fellowship in Alzheimer's disease. He is part of the CCD Memory Program based in Frontier, which is the younger-onset dementia research clinic at the Brain and Mind Centre at the University of Sydney. Ramón is a cognitive neuroscientist and a clinical neuropsychologist with expertise in neuroimaging methods and analysis. Ramón began his career studying neuropsychiatric syndromes, such as psychosis and bipolar disorder. He brings a wealth of clinical and neuroimaging experience to the project as well as a different perspective to research in dementia. As Ramón says, "It is a change of field but I still use the same expertise, techniques and analyses. I'm just applying these skills to a different disease population."

During his three-year fellowship, Ramón plans to take a comprehensive approach to studying Alzheimer's disease. He will conduct longitudinal studies of disease progression by analysing the trajectories of brains changes in a large cohort of patients with typical and atypical forms of Alzheimer's disease. He will use multimodal neuroimaging analyses that will allow him to examine molecular, macrostructural and functional brain changes over time.

Alzheimer's disease is associated with the accumulation of two proteins in the brain; amyloid and tau. The abnormal build-up of these two proteins into amyloid plaques and neurofibrillary tangles of tau lead to the loss of structure and function in the neurons and, ultimately, to the emergence of different clinical symptoms. However, the precise nature of the relationship between amyloid, tau and neurodegeneration is still not well understood. For instance, up to 30% of people with amyloid plaques never develop the disease. Further, the brain sites of amyloid aggregation and neurodegeneration diverge. Interestingly, post-mortem studies have found that people with atypical Alzheimer's disease often have larger deposits of abnormal tau proteins than those with typical Alzheimer's. Moreover, tau burden is a better correlate of disease severity and the neurodegenerative pattern. Sadly, there is currently no way to trace tau accumulation in-vivo in the clinic.

Ramón will use a combination of non-invasive neuroimaging techniques to trace the location and spread of both types of proteins in the brain, and their relation to structural and functional neurodegeneration. Changes in the brain will also be mapped onto behavioural changes to better understand the disease's clinical progression.

One of the challenges of this approach is the amount of data that it generates. As Ramón explains, "One single-modality (i.e., structural) brain scan can generate hundreds of thousands of data points. We plan to examine hundreds of individuals across different imaging techniques and across time, so the amount of data will escalate very rapidly." To manage and analyse such a massive amount of information, he will collaborate with biostatisticians and use big-data statistical techniques such as machine learning. This will also enable him to predict disease progression based on individual brain scans.

This innovative research program brings together an unprecedented amount of information and new approaches to improve our understanding of the disease. Hopefully this will assist with the development of better diagnostic and prognostic tools and the development of reliable brain markers to test drugs interventions. As Ramón says, "Dementia is a formidable enemy, but I really think we are on the cusp of finding something that will change the lives of patients and their carers."

Keep up-to-update with the latest in Ramón's research and all the work at the Brain and Mind Centre at the University of Sydney on Twitter: @Frontier_USyd and @BrainMind_Usyd.

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Telephone: +61 2 9850 4127
Email : ccd@mq.edu.au
Web : www.ccd.edu.au

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