Dementia More Closely Linked to Infections than Autoimmune Diseases

Exposure to infections is associated with an approximate 50% increased incidence of dementia in older adults, according to new research that which also observed a dose-dependent relationship between the 2 clinical outcomes.

New research from a team of Denmark investigators observed that the link between infection and dementia incidence among adults ≥65 years old is itself more than 10-fold greater than the link between autoimmune disease and dementia, thereby suggesting cognitive decline in older adults may be more impacted by infection-specific process roles than the previously hypothesized systemic inflammation role.

Investigators led by Janet Janbek, PhD, of the Danish Dementia Research Center in the department of neurology at Copenhagen University Hospital-Rigshospitalet, sought to interpret the associations of both infections and autoimmune diseases with subsequent incidence of dementia in impacted patients. They additionally observed potential shared signals presented by the immune system in the 2 conditions.

The debate into the role of infections’ causal link to dementia and cognitive conditions including Alzheimer disease has been “extensive,” Janbek and colleagues wrote. Epideimological research has been limited by the specificity of analysis into infection types, the temporality nature of postmortem analyses, and the brief follow-up periods and selective patient populations generally characterizing such research.

All the same, the robust literature supporting the role of systemic inflammation in increased dementia risk includes an inconclusive hypothesis regarding the causal role of peripheral systemic inflammation.

“By investigating infections and autoimmune diseases together, we aimed to explore potential shared signals presented by the immune system in these different but mainly inflammatory conditions that could advance knowledge on their roles as dementia risk factors and on the possible underlying mechanisms,” the team wrote.

Janbek and colleagues conducted a nationwide, population-based, registry-based cohort analysis between 1978 – 2019. Their cohort included Danish residents born 1928 – 1953, alive and in Denmark beginning in 1978, and at age ≥65 years old. Exclusionary criteria included those with prior registered dementia and those with HIV infections.

The team sought individual exposures of hospital-diagnosed infections and autoimmune diseases in their analysis from May 2022 – January 2023. Their primary outcome was all-cause dementia, defined as the date of a first registered diagnosis for dementia after age 65 years old.

Their final assessment included nearly 1.5 million individuals; 51% were women. In >1.4 million follow-up years, 45% of individuals were diagnosed with infections, 9% were diagnosed with autoimmune diseases, and 5% were diagnosed with dementia.

A majority of individuals with infections were men (51%), while a majority of individuals with autoimmune diseases were women (61%). Janbek and colleagues reported a dementia incidence rate ratio (IRR) of 1.49 (95% CI, 1.47 – 1.52) among individuals with a history of infection—a ratio increasing with increasing rates of infections.

Autoimmune disease was only associated with a 4% increased incidence rate of dementia (IRR, 1.04; 95% CI, 1.01 – 1.06), and without a dose-dependent increase. Pemphigus/psoriasis (IRR, 1.17; 95% CI, 1.09 – 1.26), anemia (IRR, 1.17; 95% CI, 1.04 – 1.32), and multiple sclerosis (IRR, 1.15; 95% CI, 1.01 – 1.30) carried the greatest incidences of dementia among observed autoimmune diseases.

“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,” investigators noted. “Importantly, this is the first study, to our knowledge, to assess the 2 exposures in 1 nationwide cohort, allowing us to draw insights that will advance knowledge on their roles as risk factors for dementia development and on the possible underlying mechanisms.”

The team concluded that their findings elucidate a possible role of infection-specific processes in the development of dementia, as opposed to general systemic inflammation. They recommended future research in a single setting be conducted to observe underlying mechanisms contributing to dementia risk any further.

Reference

Janbek J, Laursen TM, Frimodt-Møller N, et al. Hospital-Diagnosed Infections, Autoimmune Diseases, and Subsequent Dementia Incidence. JAMA Netw Open. 2023;6(9):e2332635. doi:10.1001/jamanetworkopen.2023.32635