Dennis Chan

Research Summary

My main research focus is on the early detection of Alzheimer’s disease (AD) prior to symptom onset, since this is critical to the future success of pharmacological and non-pharmacological interventions in delaying or preventing the onset of dementia. This approach centres on application of tests probing the function of the entorhinal cortex (EC) and hippocampus, as the first brain regions affected in AD.

Using VR- and tablet-based tests of spatial navigation and memory developed by Neil Burgess’ group at the ICN, my group have shown that these spatial behaviours are highly sensitive and specific for early AD and may be affected in AD prior to other cognitive functions including memory.

Current work builds on this in several ways. We will be applying these spatial tests to the world’s largest cohort of people with autosomal dominant AD, based in Colombia, to determine whether impaired navigation is the first clinical manifestation of AD. In an asymptomatic middle-aged UK cohort at risk of AD we will combine VR testing with 7T MRI to look at structural and functional imaging changes in the EC at subdivision level resolution. Working with design engineers in Cambridge and public-patient initiative experts in Newcastle, I lead a multi-centre UK study aiming to redesign the spatial tests for use in routine clinical practice, with development and trialling of app- and AR-based tasks suitable for use across diverse communities. Finally, with Karen Duff (UCL UK Dementia Research Institute), John O’Keefe (UCL Sainsbury Wellcome Centre) and Julija Krupic (Cambridge) I co-lead a translational study examining EC-hippocampal function across animal models of AD and human cohorts, establishing the relationship between tau spread, grid cell dysfunction and impaired navigation in AD. This work will address the major knowledge gap concerning the link between pathology at the cellular level and the onset of the clinical disorder, representing one of the main barriers to progress in AD research.

Separate to the above I am one of the scientific leads on a large national initiative aiming to deliver next generation digital technologies for early detection of neurodegenerative disease, with a particular interest in the use of ear-EEG for at-home deployment and use of apps for passive sensing of real life activities such as sleep and navigation. I also lead a national study trialling cognitive rehabilitation as a treatment for cognitive impairment (“brain fog”) in long Covid.

Away from UCL I work as a consultant neurologist and runs a cognitive disorders clinic in mid-Sussex with a special focus on patients with mild cognitive impairment.

My research is funded by the UK National Institute for Health Research, UK Dementia Research Institute, Alzheimer’s Research UK and the Wellcome.