ENCRYPT2

• Research type

  Research Study

• Full title

  The ENtorhinal CoRtex-hippocampal circuit in PREVENT Study 2 (ENCRYPT2)

• IRAS ID

  324204

• Contact name

  Dennis Chan

• Contact email

  dennis.chan@ucl.ac.uk

• Sponsor organisation

  University College London

• Duration of Study in the UK

  2 years, 0 months, 1 days

• Research summary

  Aim: to determine the biological basis for the onset of cognitive decline in Alzheimer's disease (AD).
  Hypothesis: spatial navigation and memory impairments are the first cognitive changes in AD, caused by tau pathology and associated neurodenegerative changes in the entorhinal cortex and hippocampus

  This project investigates the entorhinal cortex and hippocampus, the first brain regions to show degeneration in AD, in middle-aged people without symptoms but at risk of AD. Entorhinal-hippocampal function will be tested using virtual and augmented reality (VR and AR) tests of spatial navigation and memory. High resolution 7T MRI scanning will look at associated changes in structure and connectivity. Tau-PET radioligand imaging of pathology will look at associated levels of AD pathology. Polygenic risk scores will be used to establish individual participant risk profiles for late-onset Alzheimer's disease.

  The use of VR spatial navigation tests builds on previous work showing that they are more sensitive to early cognitive changes in the PREVENT cohort. They offer two key advantages to research in AD:

  i) VR navigation tests supersede current pen-and-paper/iPad tests which have limited relevance to everyday activity. We will use VR to test a real life function - remembering how to get from A to B – and getting lost occurs early in AD.

  ii) The tests are based on the Nobel Prize-winning discovery that entorhinal and hippocampal brain cells encode space akin to a 'GPS'. As such they provide a crucial bridge between lab-based work on disease effect on brain cells and the onset of clinical AD in humans.

  If this study is successful then this will aid determination of those individuals at the beginning of AD who would benefit most from future treatments aimed at delaying or preventing the onset of dementia.

• REC name

  London - City & East Research Ethics Committee

• REC reference

  24/PR/0094

• Date of REC Opinion

  6 Feb 2024

• REC opinion

  Favourable Opinion