Title: Cortical Disarray Measurement- A novel and promising tool to predict progression amongst patients presenting with mild cognitive impairment
Funder: Department of Health and Social Care

Abstract: This project tests whether Cortical Disarray Measurement (CDM) technology can demonstrate clinical effectiveness as a tool to support a more certain diagnosis for patients suspected of Mild Cognitive Impairment (MCI) due to Alzheimer s Disease (AD), and deliver a positive health economics outcome. CDM was developed by Dr Steven Chance and Prof Mark Jenkinson using extensive research datasets, results published in peer review journals. The next step is to demonstrate effectiveness in a real-world clinical setting. Objective one is to demonstrate clinical effectiveness. WP1 generates CDM results from MRI scans for 100 participants in the existing (BRAIID) study and compares to clinical assessments. This provides a checkpoint that CDM can distinguish groups as expected and an early opportunity to publish results WP2 generates CDM values from MRI scans (timepoint 1) for a cohort of 200 patients recruited in Southampton and Cardiff, suspected to have MCI due to AD. CDM results and predictions for speed of disease progression will be compared to patient performance in cognitive testing over 2 years and analysis of MRI scans taken 24 months later (timepoint 2). Objective two is to optimise the presentation of CDM results and other MRI scan data to support clinical decision making, and to communication with patients and their family. Objective three is to define current patient pathways and the impact of improved diagnosis on patient outcomes, and to deliver a national health economics analysis across primary, secondary and social care. The project lasts 36 months, with patient recruitment starting early for WP2 with follow-up scans taken after 24 months. This project will provide vital real-world clinical evidence to support regulatory submissions and clinical acceptance. A positive health economics case will support NHS adoption. Patient and public involvement is centre to the project so that benefits are maximised for patients and their families.

Lay abstract: Before a person is diagnosed with Alzheimer s Disease (AD) dementia, they may be diagnosed with Mild Cognitive Impairment (MCI). This is when they start to experience problems with memory, language, thinking and judgment that are worse than expected with normal ageing. However, MCI does not always lead to dementia. Not knowing can cause uncertainty and worry. Doctors and people with MCI agree that a more accurate test is needed. Someone with early AD may (in the future) be helped by new treatments that slow the disease. Even now, they would benefit from using the best drugs available to improve their quality of life. Families can plan together, and patients can spend longer at home before needing to move into a care setting. Oxford Brain Diagnostics Ltd (OBD), is developing Cortical Disarray Measurement (CDM) technology. We use normal MRI brain scans, but CDM allows clinicians to look in greater detail at the brain structure, revealing microscopic changes taking place in the &ldquo;grey matter&rdquo;. These changes can normally only be seen in brain tissue through a microscope after a person has passed away. This project aims to demonstrate that we can use CDM on scans from NHS patients to identify those who have MCI due to AD, and predict how quickly their symptoms will get worse. We want to understand how our technology can best help doctors and patients, and explore if spending more money on brain scans early will result in overall savings for patient care. We will work with the University of Southampton who have lots of experience helping people suffering from MCI. Using the best technology currently available they can identify 50-60% of those people likely to get significantly worse within 2-years, but we believe CDM will identify at least 80%, and hopefully 90% of these people. First we test CDM on brain scans of people already involved in research in Southampton, before recruiting a further 200 new people with MCI from Southampton and Cardiff to investigate the power of CDM to identify those people that have MCI due to AD, and separate out those that will get significantly worse over 2-years. The NIHR Community Healthcare MIC will interview clinicians, people with MCI or dementia and their carers to understand what the impact of knowing the diagnosis earlier would be. Health economists will conduct a detailed analysis of health outcomes and costs vs. benefits across the NHS and social care providers. OBD will talk to doctors and patient groups to make sure that the user interface and results provided not only help doctors make a more certain diagnosis, but can be used to explain to people with cognitive problems, and their family, the status of the disease.

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL