Cerebral amyloid angiopathy and intracerebral haemorrhage: community-based cohort study, biobank, and record linkage

This research is about cerebral amyloid angiopathy, which is known as ‘CAA‘ for short. In CAA, a protein gradually damages blood vessels in the brain. CAA can be found in elderly people who are healthy, who have dementia, or who have stroke due to brain haemorrhage.
This research aims to find out how CAA causes brain haemorrhages, how to recognise CAA in people with brain haemorrhage before they die, and what predicts whether someone who survives brain haemorrhage might have another one.
The research will: (1) recruit adults with brain haemorrhage in one community, (2) obtain consent to collect information about them, their brain scans and their brain tissue, (3) compare them to people without brain haemorrhage in another MRC study, (4) compare different types of brain haemorrhage to eachother, and (5) study the outcome after different types of brain haemorrhage in one country.
This research might benefit patients by finding out why brain haemorrhage happens, how to recognise its cause, and who is most likely to have it again. This could help identify ways of preventing brain haemorrhage in future, which will become more common as the population ages. Studying ageing is one of the MRC‘s two research priorities.

Background: Spontaneous intracerebral haemorrhage (ICH) affects ~1.5 million adults in the world each year. Unlike ischaemic stroke, the incidence of ICH is not declining and does not have specific treatments. Most ICH occurs in people aged ?70 years, and ICH incidence is likely to rise in ageing societies. Deposition of amyloid in cerebral vessel walls, known as cerebral amyloid angiopathy (CAA), is more common with age and in people with dementia. CAA is often inferred to be the cause of ICH in the brain‘s lobes, but the strength of the association between CAA and lobar ICH, the causal pathway(s), accuracy of diagnostic criteria for ICH due to CAA, and best preventive strategies are unclear.
Aim: To better understand how CAA causes ICH, develop diagnostic criteria to identify patients who have CAA underlying ICH, and determine factors influencing prognosis. This stratified medicine approach will inform the design of secondary prevention trials. The objective is to promote healthy ageing (an MRC research priority theme).
Design: Community-based ICH biobank, nested within a population-based study.
Methods:
(1) Using multiple, overlapping sources of case ascertainment I will find incident cases of ICH in a community-based cohort study, and create a biobank of clinical and radiographic data and brain tissue (44% consented to donation so far). I will investigate the association between CAA and lobar ICH in case-control comparisons with the community-based MRC Cognitive Function and Ageing Study (CFAS). I will determine the accuracy of different diagnostic criteria for CAA associated with lobar ICH in my community-based ICH study, using blinded comparisons of clinical criteria, imaging, and cerebrospinal fluid biomarkers to an autopsy reference standard.
(2) I will establish two novel record linkages, from a Scottish population-based ICH dataset to national prescribing data and digital brain images, to perform multivariable analyses of clinical, imaging, and therapeutic influences on prognosis after ICH. Estimates of treatment effect and potential recruitment rates will help design trials to improve ICH outcome.
Scientific and medical opportunities:
Unique ability to link population-wide clinical, brain imaging and prescribing data.
Efficient and cost-effective methods using existing NHS data and international collaborations.
Expertise in my institution in stroke medicine, brain banking, brain imaging, epidemiological methods, trials methodology research, and nurturing and training clinical academics.
Promising recruitment and tissue donation rates to my community-based ICH biobank.
Data and tissue collected will enable me to take a stratified approach to deep ICH.