Summary: A large-scale study has found that severe, hospital-treated infections are significantly associated with an increased risk of dementia. By analyzing nationwide Finnish health registry data of over 374,000 individuals, researchers identified 29 diseases linked to dementia risk—including 27 non-infectious conditions like Parkinson’s and alcohol-related disorders.
Crucially, the link between infections (such as urinary tract infections and unspecified bacterial infections) and dementia remained strong even after adjusting for these other 27 health conditions. The researchers suggest that while they cannot yet prove a direct cause-and-effect relationship, severe infections may accelerate underlying cognitive decline in the years leading up to a diagnosis.
Key Facts
- Independent Risk: Less than one-seventh of the dementia risk associated with severe infections could be attributed to other pre-existing health conditions, suggesting infections are a standalone risk factor.
- The Five-Year Window: On average, dementia-related infections occurred 5 to 6 years before a formal dementia diagnosis.
- Early-Onset Vulnerability: The link was even stronger for those diagnosed with dementia before age 65, with five types of infections—including pneumonia and dental caries—showing a significant association.
- Specific Infection Triggers: Hospital-treated cystitis (UTIs) and bacterial infections of unspecified sites were the most robustly linked to late-onset dementia.
Source: PLOS
Severe infections increase the risk of dementia independently of other coexisting illnesses, according to a new study published March 24th in the open-access journal PLOS Medicine by Pyry Sipilä of the University of Helsinki, Finland, and colleagues.
Severe infections have been linked to an increased risk of dementia. However, it has been unclear whether this association is explained by other coexisting, non-infectious diseases that predispose people to both infections and dementia.
In the new study, researchers used nationwide Finnish health registry data covering more than 62,000 individuals aged 65 or older who were diagnosed with late-onset dementia between 2017 and 2020, along with more than 312,000 matched dementia-free controls.
Taking a broad approach, they examined all hospital-treated diseases recorded during the previous twenty years, identifying 29 diseases that were robustly associated with increased dementia risk. Nearly half (47%) of dementia cases had at least one of the 29 identified diseases before their diagnosis.
Of those diseases, two were infections: cystitis (a urinary tract infection) and bacterial infection of an unspecified site. Among the non-infectious diseases, the strongest associations with dementia were seen for mental disorders due to brain damage or physical disease, Parkinson’s disease, and alcohol-related mental and behavioral disorders.
When the researchers then adjusted for all 27 non-infectious dementia-related diseases identified, the association between both infections and dementia remained largely intact. Less than one-seventh of the excess dementia risk among individuals with hospital-treated cystitis or bacterial infections was attributable to pre-existing conditions.
The link between infections and dementia was even stronger for early-onset dementia (diagnosed before age 65), where five types of infection—including pneumonia and dental caries—were associated with elevated risk.
The study was limited by the lack of baseline cognitive assessments and clinical examination data before dementia diagnoses, as well as a lack of data on infection treatments.
“Overall, our findings support the possibility that severe infections increase dementia risk; however, intervention studies are required to establish whether preventing or effectively treating infections yields benefits for dementia prevention,” the authors say.
The authors add, “We found 27 diverse severe, hospital-treated diseases that were robustly associated with an increased risk of dementia. Two of these diseases were infections, namely urinary tract infections and unspecified bacterial infections.”
“In our study, dementia-related infections occurred on average 5 to 6 years before dementia diagnosis. Given that the development of dementia often takes years or even decades, these findings suggest that severe infections might accelerate underlying cognitive decline.
“However, as these findings were observational, we cannot exclude the possibility that some unmeasured confounding factors might also have affected our findings. Thus, we cannot prove cause and effect.”
“Ideally, intervention trials should examine whether better infection prevention helps reduce dementia occurrence or delay the onset of this disease.”
Key Questions Answered:
A: This study specifically looked at severe, hospital-treated infections. While everyday sniffles weren’t the focus, the data suggests that infections severe enough to require significant medical intervention are the ones linked to future cognitive decline.
A: Researchers believe severe infections cause systemic inflammation. This “biological storm” can cross into the brain, potentially damaging neurons or accelerating the buildup of plaques already present in the early, silent stages of dementia.
A: It’s a strong possibility. The researchers are calling for new trials to see if better infection prevention and more aggressive treatment can actually delay or prevent the onset of dementia in high-risk groups.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neurology research news
Author: Claire Turner
Source: PLOS
Contact: Claire Turner – PLOS
Image: The image is credited to Neuroscience News
Original Research: Open access.
“The role of noninfectious comorbidities in the association between severe infections and risk of dementia in Finland: A nationwide registry study” by Adriana Michalak, Davide Marzoli, Francesco Pietrogiacomi, Damiana Bergamo, Valentina Elce, Bianca Pedreschi, Giorgia Mosca, Alessandro Navari, Michele Emdin, Emiliano Ricciardi, Giacomo Handjaras, and Giulio Bernardi. PLOS Medicine
DOI:10.1371/journal.pmed.1004688
Abstract
The role of noninfectious comorbidities in the association between severe infections and risk of dementia in Finland: A nationwide registry study
Background
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.
Methods and findings
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.
Conclusions
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.
