Longevity Briefs: Repurposing Existing Drugs To Lower Dementia Risk

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

Dementia is a ticking time bomb for the world, with the number of people living with dementia projected to nearly double every 20 years. Unfortunately, current treatments for dementia are very limited and mostly focus on symptom management rather than curing the underlying disease mechanisms. That’s partly because, as much as these conditions have been studied, we still don’t understand exactly what causes them.

One strategy for finding new dementia treatments is to look for dementia drugs that have been hiding right under our noses. It is not uncommon for existing treatments for one disease to have unexpected benefits in another seemingly unrelated condition – we just have to look for them by analysing large datasets. In this paper, researchers review all of the studies so far, searching for existing medications that might influence dementia risk.

The discovery:

Researchers selected 14 studies, involving over 130 million participants and more than 1 million dementia cases. These were studies that used various data sources to search for relationships between use of certain drugs and subsequent risk of dementia.

• Reduced Risk: Certain treatments such as antimicrobials, vaccines and anti-inflammatory drugs, were associated with reduced dementia risk. For example, vaccines for hepatitis A and typhoid were linked to lower dementia incidence.
• Increased Risk: Drugs like antipsychotics, diabetes drugs and vitamins and supplements were associated with increased risk.
• Inconsistent Findings: There were inconsistencies in identifying specific drugs that modify dementia risk, particularly in the case of antihypertensives and antidepressants. Some of these drugs appeared to decrease risk while others were associated with increased risk, despite being within the same class.

The implications:

Before you stop taking your diabetes medication, it’s important to stress that there are significant confounding factors in these studies that are likely to explain a large part of the increased risk with many drugs, even despite efforts to control for them. For example, diabetes and high blood pressure increase the risk of dementia, so it’s not surprising that people taking medications for these diseases get more dementia later on. Likewise, mental health problems can be early consequences of undetected dementia.

What’s more interesting is that certain drugs like antihypertensives were sometimes associated with increased risk, but at other times with decreased risk. This might result from different mechanisms of action of drugs designed to treat the same condition, or whether specific drugs are able to reach the brain or not. Some drugs are also not used until a disease gets worse, which will of course associate the use of that drug with more negative outcomes.

Another intriguing finding is that drugs that deal with inflammation and infection generally seem to be associated with reduced risk. Some of this may also be explained by confounding factors, such as people who get vaccinated being more trusting of modern medicine and therefore more likely to be healthy in other ways. However, there are also possible mechanistic explanations for this risk reduction, such as inflammation or severe infection contributing to dementia risk. As ever, we are going to need more data, but in the meantime these studies add credence to the idea that keeping inflammation suppressed could help to prevent dementia.