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Study sheds light on longstanding debate

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Researchers have known for decades that inflammation accompanies Alzheimer鈥檚 disease (AD) brain lesions. Several early studies suggested that 鈥渟uper-aspirins鈥� or Nonsteroidal anti-inflammatory drugs (NSAID) could help avoid the disease. However, after clinical trials showed that NSAIDs don鈥檛 help patients who already have AD symptoms, doctors wondered whether these drugs could still be helpful to people who were at risk of developing the disease, but weren鈥檛 yet showing symptoms.

To test this hypothesis, researchers at 鲍鱼直播鈥檚 Faculty of Medicine developed a new approach to AD prevention trials, and used it to test whether the common NSAID naproxen could indeed stop the disease in its tracks, before people developed AD symptoms. Sadly, the results were not encouraging, according to research published in the April 5, 2019, online issue of 庐, the medical journal of the American Academy of Neurology.

鈥淭o 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,鈥� explains Dr. John Breitner, Professor of Psychiatry at 鲍鱼直播 and the study鈥檚 senior author. 鈥淭he resulting trial, known as INTREPAD, examined the effects of naproxen in people who had a strong family history of AD but 鈥榮queaky-clean鈥� memory and other cognitive abilities.鈥�

Developing a new method to assess effectiveness

Many researchers have noted the special challenge of measuring disease development at a time when they could not rely on symptoms to assess effects of a treatment. To deal with this challenge the 鲍鱼直播 team collaborated in developing a new Alzheimer Progression Score (APS) that was shown elsewhere to predict the onset of clinical disease over the coming decade or more. The APS measures the early development of disease by combining many little changes into a composite score.

Applying the APS to a trial sample of 200 people (100 assigned to naproxen and 100 to placebo), the INTREPAD results showed real changes over the two-year trial period. However, there was no evidence that the APS change was reduced in those taking naproxen. 鈥淭he usual side effects were there,鈥� notes Pierre- Fran莽ois Meyer, a PhD candidate in Dr. Breitner鈥檚 lab and the study鈥檚 first author, 鈥渂ut there was not the slightest suggestion of any benefit.鈥�

鈥淲e think this is the end of the road for the use of NSAIDs for treatment or prevention of Alzheimer鈥檚 disease, and it suggests a need for caution about using other anti-inflammatory drugs for this purpose,鈥� adds Dr. Breitner, who is Founding Director of the Centre for Studies on Prevention of Alzheimer鈥檚 Disease at the Research Centre of the Douglas Mental Health University Institute. 鈥淭he world desperately needs a way to prevent this horrible disease,鈥� he says, 鈥渁nd many other avenues are being investigated.鈥� In this process, researchers argue ever more strongly for the importance of publishing negative or 鈥渘ull鈥� trial results like this one.

鈥淚NTREPAD: A randomized trial of naproxen to slow progress of presymptomatic Alzheimer disease,鈥� by Pierre-Fran莽ois Meyer, John Breitner, et al, was published online in the journal 狈别耻谤辞濒辞驳测庐 on April 5, 2019 doi:10.1212/WNL.0000000000007232

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Contact:

Jason Clement
Communications Officer,
Faculty of Medicine,
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514-398-5909
Jason.clement [at] mcgill.ca