Hospital-treated cystitis and bacterial infection of an unspecified site were associated with an increased risk of dementia in a nationwide Finnish registry study of older patients, with associations remaining after adjustment for noninfectious comorbidities. As an observational study, the findings do not establish causality.
Researchers analyzed 62,555 patients aged 65 years or older with incident dementia diagnosed between 2017 and 2020 and 312,772 matched controls using incidence-density sampling. Hospital-treated diseases were assessed during a two-decade exposure window occurring 1 to 21 years prior to dementia diagnosis. Models were adjusted for education, marital status, employment, and region, with matching accounting for age and sex.
Among 170 diseases with at least 1% prevalence prior to dementia, 29 were associated with an increased risk of dementia, including mental, neurological, cardiometabolic, and injury-related conditions, as well as two infections: cystitis and bacterial infection of an unspecified site.
Both infections remained associated with increased dementia risk following adjustment for all identified noninfectious dementia-related diseases, suggesting these associations were not fully explained by comorbid conditions. Comorbidities accounted for approximately 11% to 14% of the excess dementia risk associated with these infections.
The infection-associated effects were modest compared with several neurological and psychiatric conditions identified in the study, which showed stronger associations with dementia risk.
Overall, 47% of patients with dementia had at least one of the identified conditions during the exposure period. Findings were consistent across sex and education strata and remained statistically significant in sensitivity and lag analyses.
Associations were stronger for early-onset dementia. In that group, additional infections—including gastroenteritis and colitis of infectious or unspecified origin, bacterial pneumonia, and pneumonia of an unspecified organism—were also associated with increased dementia risk.
Disease trajectory analyses identified multiple interconnected conditions preceding dementia, with many of the identified diseases also associated with an increased risk of subsequent infection, highlighting complex relationships between comorbid conditions and infection risk.
The study did not include data on psychosocial, behavioral, or biological confounders not captured in nationwide registries. In addition, the long preclinical phase of dementia raises the possibility that early, undiagnosed disease may increase susceptibility to infections.
The researchers noted that infections occurred on average several years before dementia diagnosis, suggesting they may accelerate underlying disease processes rather than initiate them.
“[L]ess than one-seventh of the excess dementia risk among patients with hospital-treated cystitis or bacterial infections of an unspecified site was attributable to comorbidities, [and] the present study suggests that the associations between these infections and dementia are largely independent of prior conditions and thus supports the idea that severe infections are risk factors for dementia,” wrote lead study researcher Pyry N. Sipilä, of the University of Helsinki in Finland, and colleagues.
The researchers reported no competing interests.
Source: PLOS Medicine
