Epidemiological investigations of the role of viral infections, viral treatments, vaccination prevention and the risk of dementia

Date of Approval: 
2020-09-25 00:00:00
Lay Summary: 
A range of infectious agents have been associated with dementia, including herpes viruses, which are common viral infections. Once infection occurs, these viruses remain in the human body for life. Viruses that have been linked to dementia include herpes simplex type 1 (HSV-1, or oral herpes). This virus is very common and causes sores around the mouth and lips (sometimes called fever blisters or cold sores). In the UK, about 1% of GP consultations are for cold sores. People with cold sores can have recurrence between two and six times a year. It is estimated that 67% of people aged between 0-49 years are infected with HSV1. Antiviral medications can be used to treat the symptoms, however the benefit is small and cold sores usually resolve within 7-10 days even without treatment. Zoster herpes virus (ZHV) causes shingles in adult. Although rare, it is possible to have shingles more than once. It has been shown to link with cognitive decline. As well as viral infection, certain bacterial infections affecting the brain have been suggested also to increase the risk of developing Alzheimer’s disease. This study therefore aims to investigate the association between viral infections such as herpes simplex virus (HSV) 1, 2 and zoster herpes virus (ZHV) and dementia risk, and the effects of medications on the dementia risk, using the CPRD data. The role of vaccination against common infectious agents and their relationship to dementia risk will also be examined.
Technical Summary: 
Many studies using a range of approaches, including immunological, biological, epidemiological and GWAS (Genome-Wide Association Studies) in total approaching about 200 have implicated a range of viruses in the development of Alzheimer’s disease (AD) and dementia including herpes simplex virus (HSV)1,2 and zoster herpes virus (ZHV). We proposed to investigate if these viruses, treatments and immunisations associate with dementia outcomes. A matched cohort design will be used. Adult patients (50 years or older) with a Read /SNOMED coded diagnosis of specific infection between 1998-2018 and eligible for linkage to HES and ONS records will be matched (on age, gender and practice) with up to 10 comparison patients without the infection diagnoses. Selection will be restricted to patients registered with a contributing practice for at least one year and follow-up will end when the patient either dies, transfers out of the practice, last data collection, the end of the study period, or experiences the outcome of interest. The outcome is the first diagnosis of dementia record through CPRD, HES and ONS. Cox regressions will be used to investigate whether 1) patients exposed to infections (herpes simplex HSV1, 2 or zoster herpes virus ZHV) have a higher risk of dementia compared to those not exposed to these infections; 2) among those infected with the viruses, whether the those treated vs not treated have a reduced risk of dementia/AD; 3) investigate the association between ZHV immunisation and dementia/AD risk. In the statistical model, adjustment will be made for smoking, alcohol, BMI and Charlson comorbidity index (CCI). Missing data will be accounted for using multiple imputation.
Health Outcomes to be Measured: 
The primary outcome will be the first event of dementia and its subtypes (Alzheimer’s Disease, Vascular Dementia and Frontotemporal Dementia). Dementia outcome will be identified either in CPRD, HES or ONS. The secondary outcome will be death registration caused by dementia. Dementia death will be identified from ONS records.
Application Number: 

Darren Ashcroft - Chief Investigator - University of Manchester
Artitaya Lophatananon - Corresponding Applicant - University of Manchester
Kenneth Muir - Collaborator - University of Manchester
Krisztina Mekli - Collaborator - University of Manchester
Matthew Carr - Collaborator - University of Manchester
Rosa Parisi - Collaborator - University of Manchester

HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation