Where to begin, there was so much, and yet so little. This is my attempt to give you a snapshot of the four-day international meeting in Boston on Clinical Trials in Alzheimer’s Disease (CTAD) that I attended from November 1-4. This was their 10th meeting, but my first.
There were approximately 1,300 attendees, including: Ph.D. scientists, representatives from universities, research and clinical trial sites, academic centers, small start-up biotech companies, big pharma, advocacy groups, and caregiver organizations from almost every country in the world. All were here to emphasize the worldwide epidemic of this devastating disease.
This conference addresses the development of the next generation of Alzheimer’s disease (AD) prevention and treatment, which clearly is among the most important health needs worldwide, but continues to present huge challenges. The goal was to bring together today’s worldwide leaders in the treatment of Alzheimer’s disease to discuss new results, candidate therapeutics, and methodological issues important to the development of the next generation of treatments.
There were a number of poster presentations focused purely on diagnosis: neuroimaging markers of cerebrovascular disease in predicting cognitive impairment; brain atrophy and dementia; the use of plasmabiomarkers as a first step in a multiple process to screen preclinical AD; the possibility of automated voice-based testing to use in applications in recruitment; and developments for treatment of agitation in patients with dementia.
The meeting also featured discussions on the many different avenues being explored for treatment of AD, including considering treatments for other conditions that might translate such as: dementia and psychosis in Parkinson’s disease, treatment of rheumatoid arthritis, and insulin for diabetes. The three targets being researched are: metabolism, amyloids (plaques and tangles) and stress (inflammation).
Presenters enumerated the barriers in prevention and treatment trials: the expense, difficulties with timing, at what stage to begin, how to recruit people in early and mid-stage as well as the comparison healthy group, the need for large numbers for a long period of time, greater investment, confidentiality, privacy concerns, and risk. Media coverage of failed trials discourages participation, but patients with Alzheimer’s disease are willing to undergo trials to bring forth treatments for future generations and to be in control of their own lives.
Small variable results are often seen requiring a need to reduce variability, acquire more data, the need for cognitive testing, and an observational cohort. There was also discussion about strengths and weaknesses in academic settings versus pharmaceutical—currently 80 percent of trials are industry funded with seven at NIH and 13 at academic centers.
The need for collaboration was emphasized throughout the conference and was particularly stark. For example, a presentation by Merck on the failure of one of its compounds illustrated the need to make failures as well as successes, public—as researchers learn from both. Failures need to be published to avoid duplication and to add understanding.
There was a presentation related to the decline in amyloids related to physical activity, with lower physical activity associated with greater cognitive decline. There are a huge number of drugs in the pipeline. There are currently 54,000 trials needing subjects, 2,100 phase two trials and 300 phase three trials. Early prevention trials as well as the AD Prevention Registry needs 55,000 participants to populate 150 trials. It is difficult to enroll healthy older adults; delays in recruitment are 85-90 percent and 30 percent of studies are under enrolled. We need methods to enhance retention, At the meeting there was talk of an online registry. We need to share lessons learned, successfully engage, target drugs to specific populations, recruit low literacy, and increase representation of underrepresented populations.
There were discussions about SSRIs, amylin reducers, pimavanserin, albumin replacement and more, but there is currently no treatment for dementia-related psychosis, and the advice was to use non-drug intervention first, believing that all psychotic drugs are more dangerous and of little benefit.
There was an abundance of information, clearly indicating a continuing search for anything that would prevent, diagnose, and show improvement at early middle and perhaps later stages of the disease. The good news is that there is worldwide collaboration and many dedicated and brilliant minds working on solving this intractable disease. The bad news is that this conference is in its 10th and right now there is no end in sight.
As a caregiver, I hope that we don’t have another decade of CTAD meetings and that next year there will be more presentations focused on solutions.