Brad O’Connor, Cogstate CEO, shares the following…
Revolutionary ADRD therapeutic treatments are on the horizon for patients who are diagnosed early enough to use them. The therapeutics that are soon to be available represent a major shift in treatment options for patients with early-stage Alzheimer’s disease—but they’re not a cure. Their benefit comes from slowing down the progression of symptoms, not eliminating them. The goal has always been to find a cure, and these therapeutics are the first step to get there. Now, we’re looking at all angles to not only determine what can be done after a diagnosis—but what can be done before it.
We’re currently seeing an industry-wide push to invest in clinical trials for pre-symptomatic patients—with the goal of using disease modifying therapies in prevention trials and addressing the cause of Alzheimer’s before it causes symptoms. Having been a partner in every single pre-symptomatic ADRD clinical trial to date, Cogstate has played a pivotal role in this industry shift, and we’re seeing a few emerging trends.
Understanding the Preclinical Period is Key to Giving Patients More Time in Good Health
The preclinical period is the time before dementia can be clinically classified, and it can begin as much as 30 years before symptoms arise. Clinical pathological models provide methods and consensus criteria to allow us to identify ADRD during the pre-symptomatic period (referred to as preclinical disease), and it’s important that we use them. Every 3.2 seconds, a new case of dementia is discovered—and that’s expected to double in the next two decades. If we can detect and treat the cause of the disease before symptoms arise, we might be one step closer to preventing cognitive decline, not just mitigating it. And focusing on pre-symptomatic (preclinical) disease means we can seek treatment options years before the disease inhibits a patient’s daily life.
Pre-Symptomatic Patients Open the Door for Nuanced Clinical Trial Designs
As the demand for more pre-symptomatic clinical trials increases, we’ll need to ensure recruitment and retention efforts are well-suited for those who are cognitively well and not yet experiencing symptoms. These patients tend to be younger, working, and active in their community. They are cognitively unimpaired and aren’t usually concerned about their memory. This means they likely 1) have minimal time to join a clinical trial, and 2) don’t feel that the clinical trial’s subject matter of ADRD is applicable to them (yet). Additionally, these trials are larger, involving far more patients and their family members, and take longer, requiring a greater commitment than other ADRD clinical trials. As a solve, bringing the trial to the patient through decentralisation—conducting some or all of the clinical assessments at home with telehealth style supervision—can reduce attrition rates and burden for patients who may have otherwise busy lives.
Digital Assessments Are Uniquely Effective in Pre-Symptomatic Clinical Trials
With decades of experience in cognitive science, and through supporting pre-symptomatic clinical trials for many years, Cogstate saw an opportunity for our digital testing options. As a result, we developed a digital Preclinical Alzheimer’s Cognitive Composite (PACC) that substitutes conventional paper scales with digital scales within the same cognitive domains. The digital PACC has demonstrated validity for both in-clinic assessments and remote, supervised administration—making it well-suited for decentralised clinical trials, too. Given the lack of diversity in clinical trials, it’s essential we use effective digital tools and decentralisation to bring testing closer to the participant. Doing so increases the likelihood of participant pools being representative of the global population—ensuring clinical trial solutions work for a greater number of people. Pre-symptomatic trials also need to collect data over a long period of time, so cost reduction is critical. Digital assessments not only ensure high data accuracy and reliability, they also reduce the cost of data collection through reduced costs associated with training those professionals conducting the assessments globally.
Therapeutics Marked a Massive, Positive Shift in The Industry––and We’re Just Getting Started
Millions of people around the world are going to be diagnosed with ADRD in the next decade. We have an opportunity to make sure solutions work for as many of them as possible. By being a partner in every pre-symptomatic clinical trial to date, the team at Cogstate has seen how emerging industry tools and trends can make diagnosis and measurement less invasive and more effective at early detection for more people—which is key to giving patients agency over their brain health and supporting research that is working to bring better treatments to market.
In an ideal world, we would be able to treat the cause of ADRD prior to a patient experiencing symptoms of cognitive decline—similar to how cholesterol is cleared before it causes damage. Until that capability becomes a widespread reality, health system preparedness is key. Just because aging is inevitable, spending decades in poor health doesn’t have to be. We can, and should, invest in non-invasive, low-cost testing methodologies for non-symptomatic patients—such as annual health checks with both a cognitive assessment and blood tests to measure known biomarkers of disease, such as amyloid and tau. By doing so, we can one day treat the cause of ADRD and significantly slow or even stop cognitive decline. And if tested regularly enough, we’ll reduce long-term health care costs and caregiver burden.
A healthier future, with brain health for all, starts with understanding the makeup of ADRD long before it presents symptoms.
