Effect of major common infections on the incidence of post-stroke dementia: A cohort study using UK Clinical Practice Research Datalink

Problem

There are over 1.2 million stroke survivors in the United Kingdom. The incidence of post-stroke dementia (PSD) is estimated to be 6 – 29% and it has been hypothesised that infections play a role perhaps acting through systemic inflammation. Our study aim was to investigate whether common serious infections are associated with incident dementia in adult stroke survivors.

Approach

We conducted a historical cohort study using the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) database. A study population of patients with incident stroke aged 40+ in 2005 to 2016 time period were followed to the first incident dementia diagnosis, 5 years post-stroke, transfer out of database, death or end of study. Exposure was defined as a GP-recorded lower respiratory tract infection, urinary tract infection requiring antibiotics or a skin or soft tissue infection requiring antibiotics. The outcome was incident dementia recorded in either HES or CPRD. A multi-variate Cox regression model was developed of the relationship between any exposure to infection in the study period and the outcome of dementia.For a secondary analysis, the definition of infection was expanded to include patients who had been hospitalised with an infection as the primary diagnosis. The analysis was restricted to patients with both CPRD and HES data, and a multivariate Cox regression model was developed.

Findings

Of 60,392 patients with incident stroke (mean age 72.6 years, 51.2% male), 4512 (7.5%) developed PSD. There was a 44% increase in early dementia (3 months to 1-year post-stroke) in those who had experienced at least one major infection compared those not exposed (HZ 1.44, 95% CI 1.21 – 1.71, p<0.001). This association was not seen in late dementia (1-year to 5-years post-stroke). There was no effect modification by recurrent stroke. A secondary analysis included HES infections as a primary cause of admission to hospital as well GP-recorded major infections. This strengthened the association between infection and dementia with a 77% increase in early dementia (HZ 1.79, 95%CI 1.52 – 2.11, p<0.001) and 36% increase in late dementia (HZ 1.36, 95% CI 1.23 – 1.50, p<0.001) seen in the infection group. In late dementia, there appeared to be a linear relationship between number of infection and dementia (LRT for trend: p<0.001).

Consequences

There is some evidence of an association between major infection and PSD, however there need to be more studies to examine this relationship. Better understanding of this relationship will help to inform the development and targeting of interventions to prevent and treat infections after stroke and perhaps thereby preserve cognitive function.