The ENCRYPT study
Research type
Research Study
Full title
The ENtorhinal CoRtex-hippocampal circuit in PREVENT (ENCRYPT) Study
IRAS ID
248695
Contact name
John O'Brien
Contact email
Sponsor organisation
Cambridgeshire and Peterborough NHS Foundation Trust and University of Cambridge
Duration of Study in the UK
1 years, 0 months, 0 days
Research summary
Research Summary:
This project aims to identify the initial brain dysfunction in Alzheimer’s disease (AD) by investigating the entorhinal cortex (EC) and hippocampus, the first brain regions to show degeneration in AD, in middle-aged people without symptoms but at risk of AD. EC-hippocampal function will be tested using virtual reality (VR) tests of spatial navigation and memory, and high resolution 7T MRI scanning will look at associated changes in structure and connectivity. These tests have several advantages over current methods:1. Pen-and-paper/iPad tests 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.
2. Current tests do not distinguish between EC and hippocampal function. AD pathology spreads from the EC to the hippocampus before affecting the rest of the brain, so VR based testing of EC and hippocampal function separately could track this early spread more effectively.
3. The tests are based on the Nobel Prize-winning discovery that EC and hippocampal cells encode space. As such they provide a crucial bridge between lab-based work on disease effect on brain cells and the onset of 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.
Lay summary of study results:
1. A huge problem in Alzheimer’s disease is that dementia is diagnosed too late – up to 20 years after the disease first starts in the brain.
2. This is because current clinical assessments used by doctors are not able to detect the subtle changes in how people think when they are in the very early stages of Alzheimer’s disease. ‘Cognitive impairment’ is a term used to describe these changes in thinking.
3. Our research project aimed to find a better way to measure these early thinking changes. We investigated what the first brain region affected by Alzheimer’s disease does. Historically, researchers thought this was memory. But Nobel prize science suggests it should actually be navigation – literally how your brain acts like a ‘GPS’ to help you find your way around the world. We used a novel virtual reality navigation test designed based on this understanding, and compared performance on this to other gold standard clinical assessments in a midlife cohort with no symptoms but different risk factors for future dementia.
4. Our results showed that navigation changes, rather than memory changes, appear to be the first thinking (or cognitive) change in people who are at-risk of being in the very early stages of Alzheimer’s disease. This might enable doctors in the future to diagnose dementia earlier by providing them with new and better assessments targeting this type of thinking. Designing these new assessments is the next stage of our research project, and we hope to set up a company that can help introduce these assessments to the NHS.REC name
London - West London & GTAC Research Ethics Committee
REC reference
18/LO/2148
Date of REC Opinion
4 Jan 2019
REC opinion
Further Information Favourable Opinion