Dementia Risk Higher After Hospital Stay With Infection

Hospitalization with infection raised the risk of a subsequent dementia diagnosis, longitudinal data showed.

Among nearly 16,000 people followed for 3 decades, those hospitalized with infection had a 70% increased risk of subsequent dementia (adjusted HR 1.70, 95% CI 1.55-1.86, P<0.001), reported Ryan Demmer, MPH, PhD, of the University of Minnesota in Minneapolis, and co-authors in JAMA Network Open.

Per 1,000 person-years, dementia rates were 23.6 events (95% CI 22.3-25.0) for people who were hospitalized with infection earlier in life versus 5.7 (95% CI 5.4-6.0) for people who never had in-hospital infections.

"Infections are common and often preventable," Demmer told MedPage Today. "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."

The findings support recent research showing that hospital-treated early and midlife infections may raise the risk of neurodegenerative diseases like Alzheimer's and Parkinson's.

"Among many theorized mechanisms contributing to dementia causes, neuroinflammation has been recognized as a likely factor," Demmer and co-authors wrote.

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

In addition, longitudinal data from the U.K. Biobank has suggested that SARS-CoV-2 infection may be associated with brain abnormalities and cognitive decline, Demmer and colleagues said.

The researchers evaluated 15,688 participants who were dementia-free at baseline in the ongoing, prospective Atherosclerosis Risk in Communities (ARIC) study. ARIC participants were followed for a maximum of 32 years, from 1987 through 2019. Dementia was diagnosed in 19.0% of participants a median of 25.1 years after baseline.

Hospitalizations were determined by interviews and hospital surveillance; the main exposure was the first occurrence of hospitalization with infection according to ICD codes. Participants were considered unexposed until first hospitalization with infection and exposed after that. Dementia cases were identified through ICD codes, telephone interviews, screeners, and in-person cognitive testing for a subset of participants.

Mean baseline age of the cohort was 54.7. Overall, 55.2% of participants were women; 26.8% were Black and 73.2% were white. The cumulative incidence of any hospitalization with infection before dementia diagnosis was 38.2%.

Rates of dementia were significantly higher among people hospitalized with respiratory, urinary tract, skin, blood and circulatory system, or hospital-acquired infections. After multivariable adjustment, the top three infections linked with dementia were blood and circulatory system (HR 2.13, 95% CI 1.45-3.12), urinary tract (HR 1.98, 95% CI 1.76-2.24), and hospital-acquired (HR 1.96, 95% CI 1.52-2.51; all P<0.001).

The overall 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," Demmer and colleagues observed.

"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," they pointed out. "In addition, dementia cases occurring 2 decades after the hospitalization event are possibly less plausibly linked."

The study had several limitations including potential residual or unmeasured confounding, the researchers noted. Data about some known dementia risk factors, including mild cognitive decline, were not available. Infections that didn't result in hospitalization weren't assessed.

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