Repurposing Meds for Dementia Prevention: Will it Work?

Common drug classes that have the potential to be repurposed for dementia prevention should be prioritized for further study, new research suggests.

Some antibiotics and antivirals, certain vaccines, anti-inflammatories, and medication to treat high blood pressure and cholesterol are among the medications most associated with a lower risk for dementia, the investigators found.

“We urgently need new treatments to slow the progress of dementia, if not to prevent it,” study investigator Benjamin Underwood, MD, Department of Psychiatry, University of Cambridge, Cambridge, England, said in a statement.

“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,” he added.

The study was published online on January 21 in Alzheimer’s and Dementia: Translational Research & Clinical Interventions.

Data-Driven Approach 

Using a data-driven approach, the researchers conducted a systematic review to investigate the association between a wide range of prescription medications and dementia risk. In total, the team examined 14 studies that used large clinical datasets and medical records, capturing data from 139 million individuals and 1 million dementia cases.

Despite a lack of consistency between studies in identifying specific drugs that may modify the risk for Alzheimer’s disease (AD) or dementia, some themes emerged for drug classes with biologic plausibility, they reported.

Antibiotics, vaccines, and antivirals were associated with a reduced risk for dementia, supporting the hypothesis that infections may play a role in triggering the dementia, the researchers noted.

Anti-inflammatory medications, such as ibuprofen, were also associated with a lower risk for dementia, in line with some prior data and supporting the hypothesis that inflammation contributes to cognitive decline.

The analysis revealed conflicting evidence for several other drug classes, with some antihypertensive medications, antidepressants and, to a lesser extent, diabetes medications associated with a decreased risk for dementia. Antipsychotic medications were associated with an increased risk for dementia, as shown previously.

Caveats, Cautionary Notes 

However, just “because a particular drug is associated with an altered risk of dementia, it doesn’t necessarily mean that it causes or indeed helps in dementia,” study investigator Ilianna Lourida, PhD, University of Exeter, Exeter, England, cautioned in the statement.

“We know that diabetes increases your risk of dementia, for example, so anyone on medication to manage their glucose levels would naturally also be at a higher risk of dementia — but that doesn’t mean the drug increases your risk,” she noted.

Outside experts weighing in on the study in a statement from the UK nonprofit Science Media Centre also urged caution in drawing any firm conclusions from this study.

Kevin McConway, PhD, emeritus professor of applied statistics, The Open University, Milton Keynes, England, cautioned that this review “cannot go any further” than pointing to some classes of drugs that “might be worth investigating further, to learn more about whether and how they are associated with dementia risk.”

He noted that the review reported mostly on “broad classes of drugs rather than on specific drugs because the researchers found very few specific drugs that were associated with dementia risk in more than one of the studies they reviewed.”

Rachel Richardson, manager of the methods support unit at Cochrane, noted that “an important part of a review is an assessment of the overall certainty of the findings and this does not appear to have been carried out.”

“Assessing the certainty means considering factors such as potential biases in the included studies, whether the results are likely to reflect important clinical effects, and how relevant the findings are to different groups of people. Although the press release acknowledges the possibility of confounding, the potential impact of this cannot be overstated,” said Richardson.

Richard Oakley, PhD, associate director of research and innovation at Alzheimer’s Society, said this research provides “some initial groundwork and indicates which drugs have potential for being repurposed for dementia and should be prioritized for further investigation.”

“But we can’t draw definite conclusions from this study alone. This was an observational study so more work is needed to understand the careful balance between how the drugs work, their specific doses, interactions with other drugs and the individual’s own health, and how that can impact a person’s risk of developing dementia. Clinical trials will help to answer some of these questions in the context of dementia,” Oakley cautioned.

Francesco Tamagnini, PhD, neurophysiologist, University of Reading, Reading, England, noted that the study “strengthens our understanding that inflammation is important in how dementia develops. One interesting possibility from this research is that common anti-inflammatory medications that older people take for heart health (like low-dose aspirin to prevent blood clots) might also help protect brain function and reduce dementia risk.”

This study had no commercial funding. Underwood has been part of advisory boards for Lilly and TauRx and is part of the UK consortium designing the MASTODON adaptive platform trial in AD. All other authors declared no conflicts of interest. Richardson is employed by Cochrane. Tamagnini and McConway had no disclosures.