Previous evidence that Alzheimer’s could be prevented with an over-the-counter anti-inflammatory drug like Aspirin was refuted by a new study.
Researchers have long known that out-of-control inflammation is associated with neuron death and neurodegenerative diseases like Alzheimer’s. Earlier studies found that nonsteroidal anti-inflammatory drugs (NSAIDs) might help prevent the disease. In the past, researchers tested the idea that an NSAID like ibuprofen could halt Alzheimer’s. Those studies were stopped when they were found to not make a difference in most patients—and even caused issues like stomach bleeding in others.
For this study, published in the journal Neurology, scientists decided to test whether a simple anti-inflammatory could stop Alzheimer’s long before symptoms might show up and prevent the progression of the disease altogether. Researchers from McGill University in Montreal tested this hypothesis by observing the effect of naproxen, a common NSAID sold under names like Aleve and Midol.
“To give the NSAID story one more chance to end well, we enrolled trial participants at the earliest stages of disease development, before they exhibited cognitive impairment,” explained Dr. John Breitner, a professor at McGill and the study’s senior author. “The resulting trial, known as INTREPAD, examined the effects of naproxen in people who had a strong family history of [Alzheimer’s disease] but ‘squeaky-clean’ memory and other cognitive abilities.”
In order to test the progression of a disease that begins to show signs in the brain long before symptoms like memory, the team of researchers developed a way to rank Alzheimer’s progression, aptly called the Alzheimer Progression Score (APS). The APS combines small changes that might indicate the development of Alzheimer’s over a decade into a score.
Scientists used APS on 200 people: 100 of whom were assigned naproxen and 100 of whom were assigned a placebo. While the APS showed that patients did change over the two-year period they were observed, they were not able to draw a correlation between changes and the placebo.
“The usual side effects were there,” said Pierre- François Meyer, a Ph.D. candidate and the study’s first author, “but there was not the slightest suggestion of any benefit.”
Does that mean the NSAID theory for Alzheimer’s will finally be put to rest?
“We think this is the end of the road for the use of NSAIDs for treatment or prevention of Alzheimer’s disease, and it suggests a need for caution about using other anti-inflammatory drugs for this purpose,” said Breitner. “The world desperately needs a way to prevent this horrible disease, and many other avenues are being investigated.”
But don’t count out inflammation as a target for Alzheimer’s drugs altogether. Other scientists are still pursuing therapies that target ‘bad’ inflammation—the kind that causes neuron death and is linked to Alzheimer’s—while leaving ‘good’ inflammation responses intact. Good inflammation keeps our bodies running and helps us heal, like a fever that stimulates your body’s immune response. ‘Bad’ inflammation in the brain starts in the glial cells, which are like the janitors of the brain that typically clean up waste from cellular processes. But when the glial cells’ inflammation response gets out of control, it leads to neuron death and neurodegeneration.
Like beta-amyloid, the protein that accumulates in the brains of people with Alzheimer’s, we know that inflammation is a player in the game, but scientists don’t know what exactly causes either of the brain-degenerating factors. Even then, it’s been shown that some people have signs of Alzheimer’s in the brain, but live without symptoms into old age.
While the results of this trial were disappointing, even trials that don’t pan out can provide valuable information about avenues of drug treatment for this disease.