Assessment of common infections and incident dementia using UK primary and secondary care data: a historical cohort study

Abstract

Background: Common infections have been associated with dementia risk; however, evidence is scarce. We aimed to investigate the association between common infections and dementia in adults (≥65 years) in a UK population-based cohort study.

Methods: We did a historical cohort study of individuals who were 65 years and older with no history of dementia or cognitive impairment using the Clinical Practice Research Datalink linked to Hospital Episode Statistics between Jan 1, 2004, and Dec 31, 2018. Multivariable Cox proportional hazard regression models were used to estimate the association between time-updated previous common infections (sepsis, pneumonia, other lower respiratory tract infections, urinary tract infections, and skin and soft tissue infections) and incident dementia diagnosis. We also tested for effect modification by diabetes since it is an independent risk factor for dementia and co-occurs with infection.

Findings: Between Jan 1, 2004, and Dec 31, 2018, our study included 989 800 individuals (median age 68·6 years [IQR 65·0-77·0]; 537 602 [54·3%] women) of whom 402 204 (40·6%) were diagnosed with at least one infection and 56 802 (5·7%) had incident dementia during a median follow-up of 5·2 years (IQR 2·3-9·0). Dementia risk increased in those with any infection (adjusted hazard ratio [HR] 1·53 [95% CI 1·50-1·55]) compared with those without infection. HRs were highest for sepsis (HR 2·08 [1·89-2·29]) and pneumonia (HR 1·88 [1·77-1·99]) and for infections leading to hospital admission (1·99 [1·94-2·04]). HRs were also higher in individuals with diabetes compared with those without diabetes.

Interpretation: Common infections, particularly those resulting in hospitalisation, were associated with an increased risk of dementia persisting over the long term. Whether reducing infections lowers the risk of subsequent dementia warrants evaluation.

Funding: Alzheimer's Society, Wellcome Trust, and the Royal Society.

Figure

The association between common infections and dementia, stratified according to time since infection Time periods are overlapping. Adjusted for age, sex, patient level index of multiple deprivation, calendar period, ethnicity, smoking status, heavy alcohol consumption, anxiety and depression, severe mental illness, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, asthma, chronic kidney disease, chronic liver disease, chronic obstructive pulmonary disease, diabetes mellitus, heart failure, hypertension, obstructive sleep apnoea, stroke, traumatic brain injury, benzodiazepines, proton pump inhibitors, systemic corticosteroids, and polypharmacy. HR=hazard ratio.