In the largest systematic review of its kind, covering more than 1m cases of dementia from the records of more than 130m people, researchers found that antibiotics and vaccinations were associated with a reduced risk of cognitive problems.
Their work has supported some previously reported associations, for example, showing decreased risk of dementia with drugs to treat inflammatory disease and increased risk with antipsychotic treatment.
Antimicrobial treatment was perhaps more surprisingly associated with decreased risk, supportive of recent increased interest in this potential therapeutic avenue, they said.
The scientists suggested that while the results are not “immediately clear”, there are some intriguing patterns at play.
While associations between certain drugs and dementia risk varied quite a lot between studies, some medications like antibiotics, antivirals, and vaccines were most often linked to reduced risk of dementia.
Four vaccines in particular, including those that protect against diphtheria, hepatitis A, typhoid, and combined hep A and typhoid, were associated with a reduction in dementia risk of between 8% and 32%.
Why that might be is unclear, but the international team of researchers notes that viral and bacterial infections appear to be common risk factors for dementia, and “there is increasing interest in vaccination as being generally protective”.
“Our findings support these hypotheses and lend further weight to these agents as being potentially disease-modifying or preventative for dementia,” they concluded.
Their current research reveals only associations, so it can’t tell us what is causing dementia or if and how these medications might help to prevent it. What it can do, however, is point scientists in the right direction.
Despite decades of research and tens of billions of dollars, only a handful of new drugs have been approved for dementia. Apart from a few recent, momentous breakthroughs, most of these options only treat the disease’s symptoms, and others come with severe side effects.
As a result, some scientists have turned to already-approved drugs to see if they can be repurposed to stave off cognitive decline.
Recently, for instance, a drug that is used to induce labour was shown to protect the ageing brains of mice, and in humans, those who take popular diabetes and weight loss drugs, like Ozempic, also seem to be at a reduced risk of dementia.
But the sheer volume of available drugs is not easy to sift through.
“Pooling these massive health data sets provides one source of evidence that we can use to help us focus on which drugs we should try first,” said old-age psychiatrist Benjamin Underwood from the University of Cambridge, who led the recent review, with dementia researcher Ilianna Lourida from the University of Exeter.
Recent studies suggest dementia may be due to brain issues from high blood pressure or chronic inflammation, but further research is needed to figure out if the medications that tackle those issues are playing a role in cognitive decline, and how they are impacting that risk.
“We’re hopeful this will mean we can find some much-needed new treatments for dementia and speed up the process of getting them to patients,” Underwood said.
The authors also found anti-inflammatory drugs, like ibuprofen, may be linked to reduced dementia risk. Antihypertensives and antidepressants, meanwhile, showed conflicting results.
“If we can find drugs that are already licensed for other conditions, then we can get them into trials and – crucially – may be able to make them available to patients much, much faster than we could do for an entirely new drug.”
The study was published in Alzheimer’s and Dementia: Translational Research & Clinical Interventions.
Study details
Data-driven discovery of associations between prescribed drugs and dementia risk: A systematic review
Benjamin Underwood, Ilianna Lourida, David Llewellyn et al for the Deep Dementia Phenotyping (DEMON) Network
Published in Alzheimer’s and Dementia on 21 January 2025
Abstract
Recent clinical trials on slowing dementia progression have led to renewed focus on finding safer, more effective treatments. One approach to identify plausible candidates is to assess whether existing medications for other conditions may affect dementia risk. We conducted a systematic review to identify studies adopting a data-driven approach to investigate the association between a wide range of prescribed medications and dementia risk. We included 14 studies using administrative or medical records data for more than 130 million individuals and 1 million dementia cases. Despite inconsistencies in identifying specific drugs that may modify Alzheimer’s or dementia risk, some themes emerged for drug classes with biological plausibility. Antimicrobials, vaccinations, and anti-inflammatories were associated with reduced risk, while diabetes drugs, vitamins and supplements, and antipsychotics were associated with increased risk. We found conflicting evidence for antihypertensives and antidepressants. Drug repurposing for use in dementia is an urgent priority. Our findings offer a basis for prioritising candidates and exploring underlying mechanisms.
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