Patients who experienced a hospitalization with infection had a higher risk of a subsequent dementia diagnosis years later compared to those who had not, according to a new study published in JAMA Network Open.

Study details and key findings

For the study, researchers analyzed data from 15,688 patients who were part of the ongoing, prospective Atherosclerosis Risk in Communities (ARIC) study and dementia-free at baseline. The mean baseline age for patients was 54.7, 55.2% were women, and 73.2% were white.

Hospitalization was determined by interviews and hospital surveillance, and an incidence of hospitalization with infection was determined by ICD codes. Incidences of dementia were identified by ICD codes, telephone interviews, screeners, and in-person cognitive testing for a subset of the patients.

In total, 19% of patients were diagnosed with dementia at a median of 25.1 years after baseline. The cumulative incidence of any hospitalization before a dementia diagnosis was 38.2%

According to the researchers, patients who had experienced a hospitalization with infection had a 70% higher risk of a subsequent dementia diagnosis than those who had not.

Among patients who had been hospitalized with infection, dementia rates were 23.6 events per 1,000 person years. In comparison, patients who had never had in-hospital infections had dementia rates of 5.7 events per 1,000 person years.

After a multivariable adjustment, the three infections that were most associated with the highest risk of a later dementia diagnosis were blood and circulatory system, urinary tract, and hospital-acquired infections.

Overall, the study's findings "were consistent, and even higher, in a sensitivity analysis excluding those who developed dementia less than 3 or more than 20 years after baseline or hospitalization with infection," the researchers wrote.

"This analysis reduced the potential for reverse causality (i.e., undiagnosed dementia leading to infection) by removing dementia cases identified within 3 years of hospitalization," the researchers added. "In addition, dementia cases occurring 2 decades after the hospitalization event are possibly less plausibly linked."

Commentary

According to MedPage Today, the study's findings support recent research that shows early and midlife infections that were treated in hospitals may raise a patient's risk of neurogenerative diseases, such as Alzheimer's and Parkinson's. Other data from the U.K. Biobank has also suggested that Covid-19 infections may be associated with brain abnormalities and cognitive decline.

"Among many theorized mechanisms contributing to dementia causes, neuroinflammation has been recognized as a likely factor," the study's authors wrote.

"In the case of Alzheimer's disease, the most studied form of dementia, neuroinflammation is hypothesized to affect disease onset and progression," the authors wrote. "Several pathogenic mechanisms in the central nervous system, including astrogliosis and microgliosis, have been hypothesized to underlie Alzheimer's disease causes and progression."

Overall, "[i]nfections are common and often preventable," said Ryan Demmer, one of the study's authors from the University of Minnesota. "Our results suggest that measures to reduce the risk of infection could also reduce the long-term risk of dementia. Knowledge of historical infections could also help prioritize patients for dementia screening." (George, MedPage Today, 1/9; Bohn et al., JAMA Network Open, 1/9)