Virtual reality-based testing of entorhinal cortex and hippocampal function in people at risk of Alzheimer’s disease

The aim of this project is to detect changes in the function of the entorhinal cortex (EC) and hippocampus in people at risk of developing dementia due to Alzheimer’s disease (AD). The EC, and subsequently the hippocampus, are the first cortical regions to exhibit neurodegeneration in AD and thus detection of early alteration in their function would both aid diagnosis of AD in its very earliest stages and identify a “sweet spot” early in the disease when disease-modifying therapies may be of maximal benefit.

Knowledge of EC and hippocampal function drawn from cell and systems neuroscience will be applied to this study of early AD, specifically the extensive evidence that these regions play a critical role in spatial processing. EC (grid cells) and hippocampal (place cells) neurons have spatially-related firing activity which correlates behaviourally with spatial navigation and memory. We have already shown that spatial memory testing is highly sensitive and specific for pre-dementia AD, and this project will use immersive virtual reality (iVR) technology to assess navigation and memory in virtual environments. Subfield-resolution analyses of EC-hippocampal structure and connectivity obtained from 3T and 7T MRI scanning will provide imaging correlates of these behavioural data.

This novel approach will build on past work by i) testing EC as well as hippocampal function in at-risk cohorts, thus extending the detection of AD into even earlier stages of disease, ii) applying behavioural tests analogous to those used to test EC-hippocampal function in animal models of AD, thus addressing a major unmet need in translational AD research.

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