A scanning electron micrograph of E. coli (yellow) infecting cells within a human bladder (blue), causing them to secrete thick mucus (orange)
PROFESSOR P.M. MOTTA ET AL/SCIENCE PHOTO LIBRARY
Severe cystitis, pneumonia or tooth decay could increase the risk of dementia. A study of hundreds of thousands of people across Finland has found that people who were treated in hospital for these infections were significantly more likely to develop dementia – including an early-onset form of the condition – within the next six years.
We increasingly think that dementia, including Alzheimer’s disease, could be prevented or delayed through brain-training games, steadfast lifestyle changes and even saunas. Now, the latest research adds to the mounting evidence supporting infection avoidance to further reduce the odds of developing the condition. “It suggests that dementia risk may be partially modifiable,” says Kuan-Ching Wu at Emory University in Atlanta, Georgia, who wasn’t involved in the study.
In 2021, Pyry Sipilä at the University of Helsinki and his colleagues noticed that people who were hospitalised with severe infections were more likely to develop dementia. But it was unclear whether this was because they had other conditions like diabetes, which increases both the risk of dementia and infection susceptibility.
To untangle this, they have now analysed the health records of 62,555 people aged 65 or over who hadn’t been diagnosed with dementia in 2016, but received such a diagnosis between 2017 and 2020. These people were compared with another 312,772 individuals without dementia, whom the team matched for age, sex, education level and marital status. For all the participants, the researchers tracked any diagnoses and hospitalisations that had occurred over the previous two decades.
The team identified 29 conditions that were associated with at least a 20 per cent higher risk of developing dementia five to six years later, on average. Most of these were non-infectious, such as conditions that affect the heart or brain. But two were infections: cystitis – a urinary tract infection (UTI) that is usually caused by bacteria – and bacterial infections without a specifically affected site noted in the records. Further analyses revealed that most of the heightened dementia risk was related to these infections, not the 27 other conditions.
Although inflammation is an important immune response to infections, it is also a critical component of some types of dementia, like Alzheimer’s. Infection-related inflammation could provoke breaches in the circulatory system that affect the brain, causing microscopic bleeds or the infiltration of toxins past the blood-brain barrier, says Sipilä. Evidence is also mounting that vaccines against infections such as shingles and flu reduce our dementia risk.
In another part of the study, the researchers focused on early-onset dementia, which occurs before age 65. They found that Parkinson’s disease and head trauma seemed to raise the risk the most, but multiple infections were also implicated, with gastroenteritis, infectious or unspecified colitis (inflammation of the colon), pneumonia, tooth decay and bacterial infections of unspecified sites all roughly doubling the risk.
It is unclear why some infections are linked to early-onset but not regular-onset dementia, and vice versa, but the researchers note in their paper that the causes and genetic susceptibility associated with these forms of the condition vary.
Despite these strong associations, we don’t know whether these infections actually cause dementia, or if the team has just observed correlations, despite attempting to adjust for those, says Sipilä. “Ideally, intervention trials should examine whether better infection prevention helps reduce dementia occurrence or delay the onset of this disease,” he says.
Gill Livingston at University College London says she wouldn’t be surprised if such research confirmed a cause-and-effect relationship. “This high-quality study, in line with other evidence, the timeline and the biological plausibility make it more likely,” she says.
This could inspire better prevention, management and monitoring of severe infections, says Wu. For cystitis, for example, prevention can include ensuring adequate hydration and good incontinence care. “On the management side, prompt treatment is particularly important because UTIs in older adults often present atypically – such as confusion or delirium rather than the classic symptoms – meaning they can be missed or treated too late,” she says. “Overall, this research feels both alarming and motivating.”
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