# The role of noninfectious comorbidities in the association between severe infections and risk of dementia in Finland: A nationwide registry study

## TL;DR

This study finds that severe infections are independently linked to higher dementia risk, even after accounting for other noninfectious diseases.

## Contribution

The study demonstrates that severe infections remain significant dementia risk factors even after adjusting for 27 comorbid noninfectious diseases.

## Key findings

- Severe infections like cystitis and bacterial infections remained independently associated with dementia risk after adjusting for 27 comorbid diseases.
- 29 hospital-treated diseases were found to be robustly associated with increased dementia risk.
- The association between infections and dementia was consistent across subgroups and stronger for early-onset dementia cases.

## Abstract

Severe infections have been linked to an increased risk of dementia, but both conditions often coexist with other illnesses that may confound this association. Using nationwide Finnish health registry data, we examined the role of noninfectious mental and physical illnesses in the association between severe infections and dementia.

This register-based study included 62,555 individuals aged 65 or older in Finland in 2016 who were diagnosed with late-onset dementia between 2017 and 2020 and 312,772 dementia-free controls matched for year of birth, sex, and the follow-up period. Analyses were adjusted for education, marital status, employment, and area of residence, with age and sex accounted for through the matched conditional design and analysis. Applying a 1-year lag period, we identified 29 hospital-treated diseases that occurred 1–21 years before dementia diagnosis in cases (or index date in controls), had a prevalence of ≥ 1% prior to dementia, and were robustly associated with increased dementia risk (confounder-adjusted rate ratio ≥ 1.20, p < 0.000294). In addition to 2 infectious diseases (cystitis and bacterial infection of an unspecified site), these included 27 mental, behavioural, digestive, endocrine, cardiometabolic, neurological, and eye diseases, as well as injuries. 29,376 (47%) of the dementia cases had at least one of these diseases diagnosed before dementia. The associations between the two infectious diseases and dementia risk were not attributable to the 27 comorbid dementia-related diseases diagnosed before infections. The adjusted rate ratio for cystitis was 1.22 (95% confidence interval (CI) [1.17, 1.27]; p < 0.001) before and 1.19 (95% CI [1.14, 1.24]; p < 0.001) after adjustment for comorbidities, while for bacterial infections of an unspecified site, the rate ratios were 1.21 (95% CI [1.16, 1.28]; p < 0.001) and 1.19 (95% CI [1.13, 1.25]; p < 0.001), respectively. The findings were comparable across subgroups defined by sex and education, and stronger for cases of early onset dementia. We were not able to directly assess psychosocial, behavioural, or biological confounders that are not captured in nationwide registries.

This nationwide Finnish study identified several mental and physical diseases that are associated with an increased risk of dementia and showed that the increased incidence of dementia among individuals with severe infections is not attributable to these comorbid conditions. These results support the role of severe infections as independent risk factors for dementia.

People who experience severe infections are at higher risk of developing dementia.

It is unclear whether this association is explained by other coexisting (noninfectious) diseases that predispose to both infections and dementia.

A better understanding of dementia risk factors is needed to inform more effective strategies for dementia prevention.

Using nationwide Finnish registers, we identified 62,555 individuals aged 65 or older who were diagnosed with late-onset dementia between 2017 and 2020, and 312,772 dementia-free controls matched for year of birth, sex, and the follow-up period.

We found that in a period of 1–21 years before follow-up, 29 hospital-treated diseases were associated with an increased risk of developing dementia, many of which were also interrelated.

Two of the 29 diseases were infections, and both remained independently associated with dementia risk after adjustment for all other dementia-related diseases.

Many interconnected diseases are associated with an increased risk of dementia.

Severe infections, although linked to several other dementia-related diseases, are independently associated with higher dementia risk.

Because this study is observational, intervention trials are required to establish whether better infection prevention could reduce dementia incidence.

In a registry-based study, Pyry Sipilä and colleagues investigate the role of non-infectious mental and physical illnesses in the association between severe infections and dementia using nationwide data from Finland.