Infections, Rather Than Inflammation or Autoimmune Disease, Associated With Dementia Development

Infection exposure—rather than systemic inflammation or autoimmune disease—was statistically significantly associated with development of dementia in a dose-dependent manner in a recent study published in JAMA Network Open.

Previous studies have suggested that certain types of infections are linked to later onset of dementia, in part due to systemic inflammation. In the same breath, the proinflammatory state brought on by autoimmune diseases has also been linked to dementia in past epidemiological research. These various investigations have not produced conclusive results, however, and it remains unclear whether pathogens or infection-induced inflammation underlie dementia development. These gaps led a team of researchers to further examine the possible causal effects infections and autoimmune diseases have on dementia incidence.

Data were gathered from Danish population-based, national registries between 1978 and 2018. Patients were flagged if they had recorded diagnoses of infection or autoimmune diseases in the National Patient Register (NPR) at age 50 or beyond. Anyone with a previous record of dementia or HIV was excluded.

In total, 1,493,896 individuals were assessed: 677,147 (45%) of people registered with infections and 127,721 (9%) with autoimmune diseases. The average ages of initial exposure were 66 and 65, respectively. Respiratory infections were the most common, followed by those of the gastrointestinal and urinary tracts. As for autoimmune diseases, rheumatoid arthritis and polymyalgia rheumatica were the most prevalent.

All-cause dementia was evaluated based off diagnoses occurring from age 65 onward, and this occurred in 75,543 (5%) patients. Individuals’ age of incidence was 77 years on average.

The dementia incidence ratio rate (IRR) was analyzed within the first 5 years of initial exposures to infection or autoimmune disease and again beyond 5 years to evaluate the short- and long-term effects of these conditions.

Following infection exposure, a 1.49-fold increase was seen in dementia IRR. A significant increase was observed across nearly all measured infection sites except for cardiovascular infections. Urinary infections were associated with the highest IRR in these cases.

Autoimmune diseases were only minimally correlated with increased dementia IRR; increased incidence occurred at a rate of 1.04. These effects shrunk especially once the authors adjusted for types of infection exposure—which typically precedes autoimmune diseases.

The researchers’ results were consistent with past studies on the effects of infection on dementia development; however, there was little evidence correlating autoimmune diseases to dementia incidence.

The previous research the authors referenced speculate on the role of pro and anti-inflammatory cytokines, or dysfunction in the blood-brain barrier or peripheral-central nervous system in subsequent dementia diagnoses. Throughout this literature, “it is increasingly suggested that immune system dysregulation leading to an overactive, underactive, and/or chronic inflammatory response may play a role in the development of dementia.”

While the findings of their current study cannot support or dispute these hypotheses, they concluded by emphasizing the potential benefits of their work on future studies because “the associations of infection with dementia found in [this] study, together with the very small IRRs for autoimmune disease, may point toward a role for infection-specific processes rather than general systemic inflammation.”

Reference

Janbek J, Laursen RM, Frimodt-Møller N, et al. Hospital-diagnosed infections, autoimmune diseases, and subsequent dementia incidence. JAMA Netw Open. September 7, 2023;6(9). doi:10.1001/jamanetworkopen.2023.32635