Role of persisting neurotropic viruses in neurological diseases of ageing (360G-Wellcome-201440_Z_16_Z)

An ageing population is one of the key societal challenges of our time. Age is the most important risk factor for stroke, the leading cause of complex disability in the UK. Dementia prevalence is predicted to double over the next 30 years, prompting recent investment of £150 million in the UK’s first Dementia Research Institute. Building on previous mechanistic studies and studies using electronic health records, the proposed research harnesses novel linkages between large biological and clinical datasets to investigate how reactivation of the common, preventable and treatable herpesviruses varicella zoster virus (VZV) and herpes simplex virus (HSV) interacts with stroke and dementia development. The proposed studies combine clinical, serological and genetic data from the UK Biobank, Clinical Practice Research Datalink, Dominantly Inherited Alzheimers Disease Network and new data collected through the NIHR BioResource to generate better understanding of the relationship and help guide intervention development and targeting. Key goals are: 1) To establish the associations between herpesvirus infections and stroke and dementia 2) To determine the population sub-groups at risk of adverse neurological outcomes following VZV or HSV reactivation and identify possible risk modifiers 3) To identify critical time points for intervention with vaccine or prophylactic antiviral agents