The use of powerful imaging techniques to capture changes in the structure and functioning of the brain forms a crucial part of the PREVENT Dementia Programme. Members of the PREVENT team from across the five study sites got together in Cambridge for a scientific meeting to share the latest progress from the various imaging components of the project.
This marks an exciting time for the study as colleagues presented some intriguing preliminary findings from the first wave of study data generated from PREVENT participants in West London. The meeting also provided the opportunity to discuss plans for upcoming analysis once recruitment to the study is completed later this year. These initial glimpses at PREVENT data give us some useful hints at areas to explore once the study is up to full strength, with 700 participants having completed their initial assessments and brain scans.
Alongside the detailed brain scan information collected within core PREVENT study visits, the imaging meeting was a great chance to catch up on the progress being made with the many imaging sub-studies and related projects. From specialised imaging of the retina in the eye to using the latest methods for measuring protein build up in the brain, the group discussed the wide array of current investigations as well as new studies launching soon. With such a comprehensive range of ways to measure and analyse brain changes, this is an exciting time to be involved with imaging in our mid-life PREVENT study cohort.
Imaging lead Prof John O’Brien hosted the meeting at the University of Cambridge and the day began with Prof Craig Ritchie, PREVENT Chief Investigator, providing an overview of progress so far and upcoming plans for the next 12 months of the project and beyond.
Current investigations
Next, Dr Li Su updated the group on the MRI brain scan analysis that has been carried out to date. This included some intriguing initial findings which triggered engaging discussions on how these might be interpreted and, importantly, which key areas to focus on when investigating the remaining baseline scans upon completion of study recruitment.
The amyloid imaging in PREVENT sub-study launched at the end of 2018 and has already recruited 50 volunteers! The study uses PET scans which employ a radioactive tracer to tag a specific molecule of interest, in this case the amyloid protein. The PET scanner can then measure the amount and location of the tracer in the brain which gives us useful information about the levels of protein present. Build-up of amyloid deposits in the brain have been associated with the development of Alzheimer’s dementia and it is thought these deposits may begin to appear many years, even decades, before symptoms are present. However, we do not fully understand the relationship between amyloid and Alzheimer’s and little is known about the early actions of amyloid in the brains of mid-life individuals at differing levels of risk for Alzheimer’s disease. Dr Stephen Carter updated the group on the key aims of the project, which is looking to complete PET amyloid scans in 300 PREVENT participants overall.
Dr Maria-Eleni Dounavi then provided a detailed update of how the huge amount of brain scan data should best be stored, accessed and shared between research sites. Dr Elijah Mak also discussed some of his preliminary work, including assessing small changes to the structure of the brain by tracking how freely and directly water molecules can move from one area to another. This method, called Diffusion Tensor Imaging (DTI), can be applied to show the health of the nerve cells tracts that criss-cross the brain connecting different brain regions.
This was followed by Dr Vanessa Raymont who is studying the head injury data collected during PREVENT visits. Ongoing analysis is exploring how self-reported blows to the head and concussions throughout life may relate to changes we can see on MRI brain scans of PREVENT participants.
The retinal imaging sub-study is running at our Edinburgh site and Dr Tom MacGillivray championed the strengths of studying the eye as a window to reveal detailed information about the health of the brain. Recruitment to the study is ongoing with over 80 volunteers having completed eye examinations so far. These highly detailed retinal images are capturing many measures of the health of small blood vessels and nerve cell layers at the back of the eye in PREVENT participants. The imaging will be repeated at future follow up visits allowing the team to assess any changes in these structures over time.
The development of sophisticated machine learning approaches is accelerating and has the potential to greatly expand the knowledge we can extract from large data sets. Joseph Giorgio from the Adaptive Brain Lab, University of Cambridge explained the pioneering approach his lab are taking towards analysis of PREVENT Data and how harnessing the power of these techniques can reveal complicated patterns and links between brain scan measurements and the many other types of health information collected in PREVENT.
Upcoming research
The exciting new ENCRYPT sub-study will be soon be opening at selected PREVENT sites. Coco Newton told the assembled group of the plans to combine virtual reality navigation tasks with detailed 7T MRI brain scans to probe the ‘GPS system of the brain’. Researchers believe the areas of the brain engaged by these tasks are among the first to be affected by Alzheimer’s disease. The ENCRYPT study will explore the ability of these novel tasks to detect these very earliest of brain changes in PREVENT volunteers
The final presentation of the day came from Paresh Malhotra who is leading the upcoming Tau PET imaging study. This research will involve participants who have already had an amyloid PET imaging returning for an additional scan to investigate the presence and location of another protein also implicated in Alzheimer’s dementia. Build-up of the Tau protein within particular brain regions is thought to more closely reflect degeneration of brain cells and deterioration in thinking and memory abilities. The ability to directly image Tau in the living human brain is a recent technological advance and this important study aims to welcome its first volunteer later this year.
Close collaboration
With so much ongoing activity and even more set to come from the huge range of imaging work taking place across the study, there was a buoyant atmosphere amongst the gathered researchers. The imaging meeting provided the perfect platform for the exchange of ideas and sharing of expert advice which will act to drive our important imaging research forward as the study progresses.
The PREVENT team are incredibly grateful to all our dedicated volunteers who continually go above and beyond to take part in these innovative sub-studies, in addition to the thorough assessments involved in the core study. None of these advances in our understanding of early brain changes related to dementia would be possible without the commitment of our wonderful group of research volunteers.
Following the success of this first dedicated PREVENT Imaging meeting, the group plan to come together again next year to share more exciting advances.
