People who experience severe infections treated in hospital have an increased risk of developing dementia later in life, but this association operates independently of other underlying conditions. Researchers reached this conclusion by analyzing the vast electronic medical records of Finnish citizens. The research results were published in a magazine PLOS medicine.
Medical experts have long observed a link between infectious diseases and cognitive decline. Proposed explanations revolve around how the immune system interacts with the central nervous system. Severe infections cause widespread inflammation throughout the body. This persistent inflammation can affect the blood-brain barrier, a dense cell layer that protects the brain from toxins and pathogens that normally circulate in the bloodstream.
When the blood-brain barrier is compromised, harmful proteins and inflammatory cells can invade brain tissue. This infiltration can promote neuroinflammation, a state of chronic immune activation in the brain. This environment is responsible for the destruction of brain cells that is a hallmark of dementia. Infections can also cause problems with blood vessels throughout the body. This can include changes in blood clotting and potential damage to the delicate blood vessels that supply oxygen and nutrients to the brain.
The biological timeline of cognitive decline complicates this situation. This condition usually develops late in life, usually after age 80. By this point, most patients are already suffering from various other physical and mental illnesses. Many age-related diseases, such as diabetes and cardiovascular disease, are known risk factors for both dementia and severe infections.
Because these risks overlap, the researchers wanted to test whether infections act alone to increase dementia risk. It remained entirely possible that the patient who developed dementia after pneumonia simply had a pre-existing heart condition that actually caused both problems. To separate these variables, the epidemiology research team began an extensive data study. University of Helsinki researcher Pili N. Sipila led the study.
Sipila and colleagues accessed health registry data from all over Finland. The dataset included 62,555 people aged 65 and older who were diagnosed with late-onset dementia between 2017 and 2020. They compared this group to a control group of 312,772 people without dementia. The researchers matched each dementia patient to five control subjects of the same sex, year of birth, and specific clinical timeline.
This epidemiological approach ensures that common variables such as age and the natural passage of time do not artificially inflate the results. Matched comparisons allow researchers to pinpoint variations that are localized to specific health events. To conduct the analysis, the researchers reviewed up to 21 years of each participant’s medical records. They intentionally excluded the year immediately preceding dementia diagnosis to ensure that cognitive decline itself was not causing other medical events.
The researchers then cataloged all the illnesses and conditions that sent these people to the hospital. Out of 170 common symptoms, the research team identified 29 specific conditions that reliably precede a diagnosis of dementia. This list included 27 non-communicable diseases. Examples range from cardiovascular diseases such as stroke, to metabolic problems such as type 2 diabetes, to mental health conditions such as severe depression and physical trauma such as head trauma.
The last two items on the list of 29 conditions were infectious diseases. These include cystitis, infections of the urinary tract, and common bacterial infections of unspecified location. Almost half of people with dementia experienced at least one of 29 conditions in the 20 years before cognitive decline. Many patients have experienced these symptoms repeatedly over many years.
Researchers mapped how these diseases are interconnected. They found a web of interrelated symptoms in which an initial diagnosis of stroke often led to a subsequent diagnosis of urinary tract infection. The majority of the 27 non-communicable diseases increase the likelihood that a patient will eventually develop one of the serious infections treated in hospital. To answer their core question, the researchers needed to isolate the statistical effects of infectious diseases alone.
They adjusted the mathematical model to account for all 27 non-infectious conditions. Even after this adjustment, the associations between the two types of infections and subsequent dementia remained strong. People who were hospitalized with cystitis had about a 19 percent relative increase in the likelihood of eventually developing dementia compared to those who avoided such infections. Unspecified bacterial infections showed a similar increase rate.
Only about 10 to 14 percent of the excess dementia risk in these patients can be explained by other physical and mental health problems. Statistical modeling shows that infection acts entirely on its own as a distinct risk factor. The research team repeated their analysis for early-onset dementia, which occurs before age 65. The sample size for this secondary study included 2,639 cases.
Researchers identified a variety of infections associated with an increased risk of early cognitive decline in this young cohort. The list included severe gastrointestinal illness, bacterial pneumonia, and severe tooth decay. As with older cohorts, the association between infections and early-onset dementia remained stable even after researchers took into account all other co-occurring medical conditions.
The exact biological reasons for the differences between early-onset and late-onset dementia remain the subject of active research. The two forms of this condition rely on different genetic and physiological bases. A comprehensive research design ensures high reliability in the final reported metrics. Finland’s health system maintains nearly complete electronic health records for its citizens, eliminating the typical biases found in studies that rely on self-reporting or recall.
Still, as an observational study, this study did not conclusively prove that the infection directly causes dementia. This finding has additional limitations regarding non-severe events. The registry records only infections severe enough to require hospital treatment. Mild respiratory infections and uncomplicated illnesses managed at home with prescribed oral antibiotics were not included in the primary dataset.
Researchers believe that in older adults, severe infections may accelerate cognitive decline rather than causing the disease in the first place. Large-scale inflammatory events can simply accelerate the deterioration of a brain that is already primed to develop dementia. Future scientific efforts will need to test whether treatment or prevention of infectious diseases positively alters the trajectory of cognitive decline. Clinical intervention trials, such as studies analyzing the long-term cognitive effects of large-scale vaccination programs, are expected to provide relevant guidance in the coming years.
The study, “The role of non-infectious comorbidities in the association between severe infectious diseases and dementia risk in Finland: a national registry study,” was authored by Pyry N. Sipilä, Kaarina Korhonen, Joni V. Lindbohm, Mika Kivimäki, and Pekka Martikainen.
