Blood-brain barrier dysfunction and risk of dementia following blood-stream infections
Award Number
MR/T023791/1Programme
Research GrantStatus / Stage
ActiveDates
1 November 2019 -31 October 2022
Duration (calculated)
02 years 11 monthsFunder(s)
MRC (UKRI)Funding Amount
£224,032.00Funder/Grant study page
MRC UKRIContracted Centre
Cardiff UniversityContracted Centre Webpage
Principal Investigator
Jonathan UnderwoodPI Contact
underwoodj7@cardiff.ac.ukPI ORCID
0000-0001-6963-2821WHO Catergories
Understanding risk factorsUnderstanding Underlying Disease
Disease Type
Dementia (Unspecified)CPEC Review Info
| Reference ID | 237 |
|---|---|
| Researcher | Reside Team |
| Published | 12/06/2023 |
Data
| Award Number | MR/T023791/1 |
|---|---|
| Status / Stage | Active |
| Start Date | 20191101 |
| End Date | 20221031 |
| Duration (calculated) | 02 years 11 months |
| Funder/Grant study page | MRC UKRI |
| Contracted Centre | Cardiff University |
| Contracted Centre Webpage | |
| Funding Amount | £224,032.00 |
Abstract
Blood-stream infections (BSI) are common life-threatening infections, a leading cause of sepsis and have a 30-day mortality in excess of 15%. Sepsis-associated encephalopathy is characterised by acute neurological dysfunction in response to extra-cranial, systemic infection – occurring in up to 70% of patients with sepsis. Its mechanisms are poorly understood but there are data to suggest an increased risk of subsequent dementia. Research questions to be answered: 1. What is the relationship between common BSI (Escherichia coli and Staphylococcus aureus) and incident dementia? 2. What are the risk factors for development of dementia following BSI with Escherichia coli and Staphylococcus aureus and do they differ by pathogen? 3. Are Escherichia coli and Staphylococcus aureus BSI associated with increased blood-brain barrier permeability? 4. Are Escherichia coli and Staphylococcus aureus BSI associated with accelerated grey and white matter atrophy? Methods: 1. Public Health Wales Escherichia coli and Staphylococcus aureus BSI data will be linked to routinely collected GP/Hospital patient data using the Secure Anonymised Information Linkage (SAIL) databank. This will take advantage of the newly created dementia e-cohort within SAIL with ~1.2 million people and 130,000 cases of dementia. Survival analysis with a proportional hazards model will then be used to compare time to dementia diagnosis in people who have had BSI compared with those who have not, adjusting for potential confounders. 2. Patients with Escherichia coli and Staphylococcus aureus BSI (n=24) and matched controls (n=12) will be prospectively recruited to a neuroimaging study where MRI scanning (high resolution T1-weighting and dynamic contrast-enhanced) will be performed shortly after and again 12-18 months after blood-stream infection to determine: a. longitudinal rates of atrophy b. blood-brain barrier dysfunction
Aims
This project aims to determine the relationship between common blood-stream infections and subsequent dementia. This will be accomplished by using routinely collected GP and hospital data throughout Wales and linking this to blood-stream infection data collected by Public Health Wales. The risk of dementia, timing of onset and potential risk factors at a population level will be established.