James Rowe, UK

Plenary session 3: A functional network approach to FTD

Presentation:

Between the genetic/environmental root causes of frontotemporal dementias, and their clinical syndromes, lies a cascade of pathogenic processes. Within this cascade, there is both convergence (e.g. on inflammation, and synaptic loss) and divergence (eg. in functional anatomy and symptoms). This cascade provides many opportunities for intervention, to treat or prevent FTD.  But, to exploit these opportunities for experimental medicine, we need tools and analytical approaches suitable to each point in the cascade. Here we focus on processes that are “downstream” of Tau/TDP43 proteinopathy and neuroinflammation – including the loss of synapses, neurotransmitters, and the resulting disruption of brain network dynamics. These are closely aligned with the changes in cognition and function that in turn influence quality of life and outcome. For observational and drug-interventional studies in FTD and PSP, we bring together synaptic PET, 7T-MR Spectroscopy, and M/EEG imaging methods, with biophysical modelling. These methods are individually sensitive to the presence and severity of FTD/PSP, but in combination they can reveal pathogenic mechanisms of human disease that have hitherto required preclinical models or post mortem methods.  These methods are ready for application in experimental medicines studies to de-risk early phase clinical trials.

Bio:

As Professor of Cognitive Neurology James studies the mechanisms and treatment of frontotemporal dementias, Progressive Supranuclear Palsy, corticobasal syndrome and related disorders. He trained in medical sciences and experimental psychology at Cambridge, before clinical training in Oxford and his PhD at UCL, London. After specialist training in London and Copenhagen, he returned to Cambridge where he now leads the Dementia theme of the NIHR Biomedical Research Centre, and directs the Cambridge Centre for Frontotemporal Dementia. He is Associate Director of Dementias Platform UK, and Chief Scientific Adviser to Alzheimer’s Research UK.  His work brings together deep-phenotyping, brain imaging, genetics, computational modelling, pharmacology and cognitive neuroscience to understand the mechanisms of disease and disease variance, as the pathway to new treatments. He is an active clinical neurologist, which underlies his determination that research focusses on the priorities for people affected by dementias. He loves the ISFTD meeting, a highlight of the academic year, with its integration of clinical- and discovery-science, and collaborative spirit.