For 18 years, more than 500 older people in the UK have donated their brains after death to track the physical causes of dementia across generations. The problem is that the method used to examine those brains—a protocol called CERAD—is 20 years old and misses many types of brain damage now known to be important. Meanwhile, lifestyles, healthcare, and nutrition have changed so much that the pathology behind dementia may itself be evolving. Without updated tools, researchers cannot tell whether today’s dementia looks different under the microscope from dementia two decades ago. This project will re-examine all stored brain tissue using a modern European protocol (BrainNet) and add biochemical measurements that standard pathology ignores. If successful, the new data should sharply improve scientists’ ability to distinguish, based on brain pathology alone, who had dementia and who did not. That clearer picture matters because it will guide the development of treatments designed to protect the brain—treatments that need to target the right pathology in the right generation. The work also keeps the CFAS brain bank, the world’s only cross-generational population-based dementia resource, scientifically viable for another decade of collaborative research.
View original technical description
Brain pathology is central to understanding dementia. For 18 years respondents in the MRC Cognitive Function and Ageing Study (CFAS), a major, prospective, longitudinal, population-based survey of mental health and frailty among older people, have donated their brains for research. The donor cohort has more than 500 completed brain examinations and provides an internationally acclaimed resource for research into the causes of dementia. In 2008 the MRC funded new clinical cohorts within CFAS (CFAS-II) to study how dementia has changed between those susceptible more than 20 years ago and today?s older people. Many changes in this period affecting lifestyles, health-care, nutrition and other factors raise the possibility that the pathology underlying dementia may evolve across generations. In an era when there is active development of innovative treatments to protect the brain and treat dementia we need as much information as possible about these changes with time. As the largest of only a handful of truly population-based studies of dementia in the world, and the only one with cross-generational cohorts, CFAS will uniquely be able to address these questions. This study has two main objectives. One is to enrol a new cohort of potential donors from CFAS-II. The second is methodological, but of vital importance to the continuing relevance and future viability of brain pathology studies in CFAS. Until now the brains have been evaluated using a method developed 20 years ago (CERAD). There have been major scientific advances in the field of dementia across this time and the CERAD protocol does not capture a range of pathologies that are now considered to be very important. It is also very imprecise about what methods should be used to demonstrate the various pathologies. Recently colleagues in Europe have formed a consortium (BrainNet) which has resolved, through validation studies, the best way to look for and evaluate brain pathologies of relevance to dementia. We propose to re-evaluate the CFAS-I donor brains, using the BrainNet protocols, to generate a new ?state-of-the-art? data set. We will also capture biochemical data which is important but not a part of standard pathology methods. We will investigate the hypothesis that this more comprehensive picture of brain pathology will significantly improve our ability to distinguish demented from non-demented people based on pathology. The data will also be invaluable to our wide range of collaborators currently using tissue from the CFAS brain donor resource.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know