Is research on Alzheimer’s disease and dementia being oversold?
Recent clinical trials have shown new drugs to fight Alzheimer’s disease, called anti-amyloids, did not significantly help patients. Other potential treatments have also failed, including those targeting the build up of Tau protein, dysfunction of the neural circuits and interconnections between brain regions, and the ordinary cellular processes involved in brain function, such as movement of nutrients within the brain and removal of waste.
It’s time to question the model of dementia research and funding that’s being energetically pursued around the world. Elevated expectations, promoted by a variety of players, have led to widespread public misunderstanding about the true state of evidence on risk reduction, early detection and diagnosis, and effectiveness of drugs.
Clinical trials haven’t produced real results for people living with Alzheimer’s disease and other dementias. And these negative results have also diminished the credibility of the leading theory of how Alzheimer’s disease works: that it is the result of a buildup of amyloid plaques in the brain.
There are currently no drugs that effectively reverse the disease, only some that slow its progression. Even how dementia develops is still poorly understood – as is the nervous system and brain in general.
We do know that about 80 percent of dementia is in people older than 75 years old. Studies suggest nearly one third of dementia is related to factors we can do something about: increases in education level and physical activity, and reductions in midlife high blood pressure, obesity, diabetes, smoking, hearing loss, social isolation and later life depression.
Yet research about these factors receives far less research attention than drug development.
Pharmaceutical companies are partially to blame. Overstating treatment and clinical benefits contributes to media hype beyond what is justified by original data. Among results reported as positive, it is often actually the case that insignificant differences have been observed between patients who did and did not receive the drug during the trial.
For example, in May 2017, the biotech company Neurotrope reported positive results for their new Alzheimer’s drug, bryostatin. Yet an inappropriate statistical approach was used, in which Neotrope reported results for only about half their enrolled patients. Excluding those using the highest doses of bryostatin allowed Neurotrope to report only desirable results, turning a negative Alzheimer’s study into a positive one.
Drug makers also market unapproved and off-label use of anti-psychotic drugs for dementia, resulting in several pharmaceutical companies being fined billions. Examples include Eli Lily, which was fined $1.5 billion in 2009 for Olanzapine; Pfizer, which was fined $2.3 billion for Ziprasidone in 2010; and Johnson & Johnson, which was fined $2.2 billion for Risperidone in 2013.
A class action lawsuit for false advertising was taken against Accera for promoting its nutritional supplement Axona “…for clinical dietary management of metabolic processes associated with mild to moderate Alzheimer’s disease” on the basis of one trial demonstrating reduced symptoms at 45, but not 90 days. In addition, there are no distinctive nutritional requirements for individuals with mild to moderate Alzheimer’s disease.
Advocates such as researchers, advocacy organizations and patient lobbyists are also partly to blame for the hype. These groups have used extreme language to describe the scale of the issue, such as, “the Alzheimer tsunami” or “the enemy at our gates.” Their efforts may have paid off. The 2013 London G8 Legacy meeting marked a critical turning point for global dementia research with its commitment to increase funding, and new research initiatives, including the Canadian Consortium on Neurodegeneration. Brain Canada also offers promises of progress to Canadians now awaiting the assent of Bill C-233 (the Federal Dementia Strategy).
At the G8 2013 Legacy meeting a pledge was made that by 2025 there would be therapies that slow or halt dementia progression or a cure for dementia. While this can attract commercial interest and investment, it does nothing to promote the science of improvements in care patients receive from family physicians, care homes and assisted living.
Exaggerated claims of ‘soon to be discovered’ cures, and ignoring uncertainty surrounding biomarker tests for Alzheimer’s and other dementias does little to help health care providers deliver better care to persons living with dementia.
Experts and advocates need to review their messages and engage the public in balanced dialogue about new discoveries and their likely importance, and to lower unrealistic expectations.
It is the duty of researchers, funding agencies, academics, drug companies and advocacy organizations alike to discuss the return on investment of dementia research in terms of short, medium and long term outcomes, taking care to ensure that continued funding of research does not come at the expense of societal responsibility.
Natalie Irene Warrick is a PhD Candidate at the Institute of Health Policy, Management and Evaluation, University of Toronto, Ontario, Canada. Carol Brayne is a professor at the University of Cambridge’s Institute of Public Health, Cambridge, United Kingdom. Larry W. Chambers is the former Scientific Advisor of the Alzheimer Society of Canada, Toronto, Ontario, Canada. Lon S. Schneider is a professor at Keck School of Medicine at the University of Southern California, Los Angeles, California, United States. Mimi Lowi-Young is the former Chief Executive Officer of the Alzheimer Society of Canada, Toronto, Ontario, Canada. Doug Brown is the director of research and development at the Alzheimer’s Society (UK), London, United Kingdom. Rupert McShane is a professor at University of Oxford and lead at Cochrane Dementia and Cognitive Improvement Group, John Radcliffe Hospital, Oxford, United Kingdom.