- Previous research suggests that severe infections may increase risk for dementia, but the involvement of other conditions can make the relationship unclear.
- One nationwide registry study conducted in Finland confirmed that while many diseases may increase dementia risk, two types of severe infections may independently increase risk for dementia.
- The researchers identified 29 diseases occurring before dementia that were linked to a higher risk of cognitive decline.
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One recent study sought to disentangle information to see if severe infection increases the risk for dementia. The study included data from over 62,000 people with dementia and controls.
Researchers were able to account for a number of conditions that also increase dementia risk, and the findings still suggest that severe infections may independently increase risk for dementia.
The findings were published in PLOS Medicine.
This study was a nationwide registry study in Finland. This allowed researchers to examine an extensive amount of data.
To start off, they identified hospital-presenting diseases that had “a prevalence of 1% or higher among dementia cases” and evaluated which increased dementia risk. Next, they examined the 20 years prior to an individual’s dementia to identify factors, such as the sequence of diseases linked to higher dementia risk.
Finally, they saw how much the link between severe infections remained after taking the other dementia-related diseases into consideration. For this study, severe infection referred to infections treated in the hospital.
Researchers focused on individuals ages 65 or older. These individuals had late-onset dementia that occurred between 2017 and 2020. Researchers matched these with controls who did not have dementia at the time individuals with dementia were diagnosed. In all, 62,555 participants with dementia and 312,772 controls were included. The average age of participants was 81 years.
Researchers also conducted an additional analysis of dementia cases diagnosed before age 65. They confirmed dementia cases by looking at hospital inpatient and outpatient records, as well as data on medication purchases and reimbursement entitlements.
They reviewed hospital inpatient and outpatient records to identify diagnoses that occurred in participants ages 1 to 21 years prior to their dementia diagnoses. They saw which diseases were associated with increased dementia risk and included those that met a certain threshold in further analysis.
Overall, they identified 29 diseases occurring before dementia that were linked to a higher risk for dementia. Some of the diseases most associated with dementia are mental disorders due to brain damage and Parkinson’s disease. Two of them were infections: bacterial infection of an unspecified site and cystitis.
Participants experienced cystitis an average of six and a half years before dementia diagnosis, and bacterial infection of an unspecified site an average of just over five and a half years before dementia diagnosis.
Researchers further examined the disease trajectory for the 29 diseases related to dementia and also analyzed whether the link between infections and dementia could be explained by the other diseases.
They found that 19 conditions appeared to increase the risk of cystitis, and 10 increased the risk of bacterial infections of an unspecified site. However, even after researchers adjusted for dementia-related diseases that happened prior to these infection types, infections still appeared to increase the risk for dementia.
The findings indicated that comorbidities explained about 11-14% of the association.
When looking at early onset dementia, researchers identified other infections in addition to bacterial infection of an unspecified site that were associated with an increased risk for early onset dementia. These findings remained significant after adjustment for other non-infectious diseases that had occurred beforehand. About one-third of the association was due to comorbidities.
Overall, the findings suggest that certain severe infections may increase the risk for dementia.
“We found that the dementia-related infections occurred on average 5 to 6 years before dementia. We also know that the development of dementia often takes several years or even decades. Thus, our findings suggest that severe infections could accelerate underlying cognitive decline,” study author and epidemiologist Pyry Sipilä from the University of Helsinki explained.
Brent Masel, MD, neurologist with UTMB, who was not involved in the study, also noted the following:
“What stands out and adds to our knowledge is that infections serious enough to result in hospitalizations can be an independent risk factor for dementia. There has been a lot of interest lately in the role of infections in the development of dementia, and this study certainly adds to the mounting evidence of that connection.”
This research included only individuals in Finland, so generalizability may be limited, and the findings should be confirmed in other groups. While this research used extensive information, missing or incorrect data remain a possibility.
Researchers also assumed, based on emigration data, that people in Finland at the end of 2016 remained in the country until the end of 2020, and only recorded individuals who died. They also assumed that all participants “remained covered by the Finnish healthcare system throughout the observation period,” while acknowledging they had ignored the potential bias from emigration. However, they note the low emigration rate among people aged 65 and older in Finland.
It’s possible that researchers didn’t properly account for certain covariates, so there is a possible risk for residual confounding. Researchers note that other non-disease events could also contribute to dementia risk.
Given the nature of the study, researchers didn’t have access to certain data, such as baseline cognitive assessments and treatment data for severe infections. They also only looked at all-cause dementia rather than examining dementia subtypes.
Researchers admit they may also have missed some associations. They also note the possibility that some controls could have actually been dementia cases, but just had a delayed dementia diagnosis, and possible bias because of delays in noting dementia in records. Preclinical dementia may also account for some of the associations they observed, potentially leading to overestimating the impact of certain conditions.
Researchers also acknowledge the possibility of reverse causation and note that severe infections “may accelerate existing cognitive decline and neuropathological processes.”
This research identified only two infection types that may increase late-onset dementia risk, so further examination of other infection types may be helpful.
The findings on infectious diseases also don’t negate the risk from other conditions, as it’s still important to address these risk factors, too.
“One must be cautious, however, in interpreting the results. Severe infections may clearly be a factor in the development of this disease, but the role they play remains just a small piece of the giant puzzle of dementia,” Masel told Medical News Today.
This research shows the importance of considering severe infections as a risk factor for dementia. However, it doesn’t mean most people need to freak out about infections.
“I think that a fully healthy person experiencing an infection should not be worried about getting dementia because of the infection. However, perhaps more attention could be given to the prevention and treatment of infections among those who are at an increased risk of cognitive decline and dementia,” Sipila noted.
Exploring infection prevention and dementia risk can be one focus of future research. Philip Keiser, MD, Associate Dean for Public Health Practice, University of Texas Medical Branch School of Public and Population Health, who was also not involved in the study, emphasized the following:
“It opens the possibility that early treatment or prevention of infections in those at risk for dementia may have a beneficial effect on this disease. However, it is critical to point out that while this study demonstrates associations, it does not demonstrate causality.”
“It will be very interesting for future research to prospectively follow people at risk for dementia to strengthen the association and to determine if prevention or early intervention can prevent this disease,” he told MNT.
