Do Infections or Autoimmune Diseases Better Predict Dementia Risk?

Among patients with hospital-diagnosed infections, infection-specific processes, rather than general systemic inflammation, may better predict dementia risk, according to study findings published in JAMA Network Open.

Previous literature has reported conflicting results regarding the link between infections and dementia. The proposed mechanism of this relationship stems from systemic inflammation caused by infections, leading to increased dementia risk. 

Researchers conducted a nationwide, population-based, registry-based cohort study to evaluate the association of infections, autoimmune disease, and dementia incidence and to determine shared signals between these conditions. The study ran from 1978 to 2018 and recruited participants from Denmark.

Participants with a prior history of dementia and HIV infections were excluded from this study. The researchers defined exposure as admission to the hospital with a discharge diagnosis of infection or autoimmune disease. In addition, participants were required to be on the National Patient Register (NPR) from age 50 and onward. 

The primary outcome was all-cause dementia, which was defined as having a dementia diagnosis after age 65.

A total of 1,493,896 individuals were screened for analysis, including 51% (n=763,987) women. Of these participants, 677,147 (45%) had infections and 127,721 (9%) had autoimmune diseases from age 50 and onward. Among the participants with infections, approximately half were men (n=343 504 [51%]) but for autoimmune diseases, a majority were women (n=77,466 [61%]).

The most common infections were respiratory, gastrointestinal, and urinary; the most common autoimmune diseases were rheumatoid arthritis and polymyalgia rheumatica. 

A total of 75,543 patients (5%) had all-cause dementia reported from age 65 and onward. The median age at dementia incidence was 77 (interquartile range [IQR], 72-81 years). 

The incidence rate ratio (IRR) for dementia following infection was 1.49 (95% CI, 1.47-1.52). The number of infections was associated with increased IRR, particularly for patients with 3 infections or more (fully adjusted IRR, 1.81; 95% CI, 1.77-1.86). Within 5 years (fully adjusted IRR, 1.83; 95% CI, 1.80-1.87) and more than 5 years (fully adjusted

IRR, 1.34; 95% CI, 1.31-1.36) after infection, the IRRs remained increased compared to participants without infection.

Except for cardiovascular infections, all other types of infections had significantly increased IRRs for dementia (fully adjusted IRR, 1.81; 95% CI, 1.78-1.85).

Following any autoimmune disease, the dementia IRR was 1.04 (95% CI, 1.01-1.06), with women experiencing slightly increased ratios (fully adjusted IRR, 1.05; 95% CI, 1.02-1.08). Unlike infections, autoimmune diseases did not have a dose-response association for disease burden.

“[T]he associations of infection with dementia found in our study, together with the very small IRRs for autoimmune disease, may point toward a role for infection-specific processes rather than general systemic inflammation,” the researchers noted. 

They concluded, “To our knowledge, this study is the first to assess all sites of infection, the long-term and short-term risks across all sites, and the burden of infection and autoimmune disease using multiple measures.”

Study limitations include the inability to assess different dementia subtypes, the inability to draw conclusions based on associations, and residual confounding factors. 

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.