Hospital-Diagnosed Infections Associated With Increased Incidence of Dementia

Hospital-diagnosed infections have previously been associated with dementia, but there is a lack of association between autoimmune diseases and dementia, according to a study published in JAMA Network Open. The authors said that this could potentially indicate infection-specific processes in developing dementia rather than systemic inflammation.

Infections were associated with a 1.49-fold increase in the rate of dementia. Although there were increases in both the short- and long-term rates, the increases were greater in the short term, according to investigators.

Autoimmune diseases were associated with a 1.04-fold increase of dementia, with the effects remaining small, especially after adjustment for infections. The investigators noted that systemic inflammation was previously associated with infections and dementia, suggesting an association between autoimmune diseases and developing the condition. They said that there have been many limitations about whether infections can be linked with dementia, but these prior studies have been relatively limited. Limitations included focusing on specific infections or pathogens, studying postmortem brains, or short follow up periods with selected population.

The study authors aimed to investigate both infections and autoimmune diseases to determine any associations as dementia risk factors or on the possible underlying mechanisms of the condition.

Investigators used population-based Danish national registries to conduct the 40-year study between 1978 and 2018. All Danish residents who were born from 1928 and 1953, were alive in Demark on January 1, 1978, and were aged 65 years were included. Individuals who had a dementia diagnosis prior to the study and those with HIV infections were excluded. Data were analyzed between May 2022 and January 2023, according to the authors of the study.

There were 1,493,896 individuals included in the study, with a follow up of 14,093,303 person-years. Approximately 45% of individuals had infections during the study period and 9% had autoimmune disease from 50 years of age and older. Additionally, 5% of individuals had all-cause dementia from 65 years of age and older.

Further, 51% of those with infections were men whereas 61% of those with autoimmune diseases were women. Investigators determined that respiratory infections were the most common, followed by gastrointestinal and urinary infections. For autoimmune diseases, rheumatoid arthritis and polymyalgia rheumatica were the most common.

The dementia incidence rate ratio (IRR) was increased for those who had infections compared to those who did not have infections, with the IRRs similar for women and men. The study authors also reported a dose-dependent manner with the increasing burden of infection. There was an increase in IRR for within 5 years and more than 5 years, according to the results.

Furthermore, there was a significant increase in IRRs across all infection sites except for cardiovascular infections. The highest incidence was for urinary infections.

For autoimmune diseases, the IRR was increased compared to those who did not have autoimmune disease, but investigators reported that this was a small increase, especially after adjusting for infection. The IRR was higher for women and there was no dose-response association.

The study authors reported statistically significant IRRs in some disease categories, however, the increases were small. There were increased mortality rate ratios for both infections and autoimmune diseases, however, the results were higher for infections.

References

Janbek J, Laursen TM, Frimodt-Møller N, Magyari M, et al. Hospital-diagnosed infections, autoimmune diseases, and subsequent dementia incidence. JAMA Netw Open. 2023;6(9):e2332635. doi:10.1001/jamanetworkopen.2023.32635