Digital Biomarkers Are Reshaping Alzheimer's Patient Experience And Data
A conversation with Christian Howell, CEO, Cognito Therapeutics
Recruiting more diverse populations while maintaining scientific rigor — that’s a goal for many clinical-stage pharma companies and biotechs these days. But depending on the therapeutic area and complexity of the trials it requires, it can be a daunting task.
What’s helping Cognito Therapeutics on this front is its embrace of biomarkers, which are seeing strong regulatory engagement and are driving a new era in Alzheimer’s clinical research. Noninvasive digital and physiological measures, including EEG-based biomarkers, now offer unprecedented precision in assessing brain function and treatment effects, broadening clinical trial accessibility and enhancing data integrity. These tools, alongside objective imaging and at-home digital assessments, enable researchers to make a major leap from traditional studies reliant on restrictive, costly amyloid thresholds that often slow enrollment and skew data.
In this interview, Cognito CEO Christian Howell shares, by way of the company’s OVERTURE feasibility study, how EEG and digital biomarkers are reshaping recruitment, patient experience, and the quality of study data in Alzheimer’s research.
Clinical Leader: The OVERTURE feasibility study did not require a specific amyloid threshold. Why was that important, and how did it impact recruitment and data integrity?
Christian Howell: OVERTURE was intentionally designed as a feasibility study focused on safety, adherence, usability, and early signal detection across the range of patients clinicians actually see in practice. Imposing a strict amyloid threshold — via PET scans or cerebrospinal fluid testing — can dramatically slow recruitment, increase screen failures, and skew enrollment toward individuals with higher socioeconomic means who can access these tests. By allowing clinically well-characterized participants without mandating a rigid biomarker cutoff, we reduced patient burden, accelerated enrollment, and created a study population that more accurately reflected the real-world population that would ultimately use a non-drug therapy like Spectris AD. Importantly, scientific rigor was maintained through objective physiological measures, prespecified analyses, and the inclusion of amyloid data where available, allowing us to evaluate treatment effects across both biomarker-confirmed and clinically diagnosed subgroups.
Was this decision made to support a more diverse patient population? What else was done to increase participant diversity, and why does it matter?
Yes. Mandatory biomarker thresholds can unintentionally exclude underrepresented communities that already face structural barriers in accessing advanced diagnostics. We took a broader, equity-focused approach that centered around clinical eligibility rather than high-cost, gatekeeping tests. Beyond enrollment criteria, we offered flexible visit schedules and transportation support and incorporated caregiver involvement and remote assessments to reduce logistical burden. The result was a more inclusive study, with faster and more consistent recruitment. This diversity strengthens external validity and helps ensure that future therapies work for and are accessible to all patients who need them.
You relied heavily on EEG-based biomarkers. What are they, and why are they meaningful relative to traditional measures?
EEG allows us to measure brain network function with millisecond precision, which is uniquely suited to studying a therapy like ours that targets neural oscillations, including gamma frequency activity. In OVERTURE, EEG captured how well the brain responded to stimulation — looking at changes in oscillatory activity, functional connectivity, and steady-state responses linked to sensory-cognitive processing. These measures are objective, repeatable, noninvasive, and far more cost-effective than imaging, allowing for dense, longitudinal sampling over the course of the study. While EEG does not replace traditional clinical or imaging endpoints, it provides a sensitive readout of neural network health that can detect changes earlier than slower-moving clinical scales. This gives us a more direct view into the underlying biology and helps guide endpoint selection for future trials.
What has including digital biomarkers done for patient recruitment, the patient experience, and the quality of study data?
Digital measures significantly lowered the burden on participants and caregivers by enabling more at-home and remote assessments, which in turn made it easier for patients to join and remain in the study. From a scientific standpoint, digital biomarkers provided richer, more continuous data that helped us track variability and behavior in ways that traditional visit-based assessments cannot. By pairing digital metrics with EEG physiology and standard clinical measures, we gained a much more complete and dynamic picture of how patients were responding over time. This integrated approach gave us insights that will inform the design of our larger pivotal trials.
How are regulators viewing the use of digital biomarkers in studies like OVERTURE?
Regulators have been increasingly supportive of digital biomarkers when they are appropriately validated and fit for purpose. Their expectations are clear: the measures must be analytically sound, clinically meaningful, prespecified in the design, and supported by robust data quality and privacy protections. Our dialogue with regulators has reflected that position. They recognize the value of digital and EEG-based measures in early studies, especially for understanding mechanism, refining dose and schedule, and informing endpoint selection for larger feasibility and pivotal programs.
About The Expert:
Christian Howell is the CEO of Cognito Therapeutics, a late-stage clinical neurotech startup pioneering noninvasive neuromodulation therapies to treat Alzheimer’s and other neurodegenerative diseases. With more than 20 years of leadership experience across startups and global medtech companies, Christian holds deep expertise in advancing innovative medical technologies from early development through market adoption.
Christian began his career as an officer in the U.S. Navy, where he developed a lifelong commitment to mission-driven organizations and work in service of others — principles that continue to guide his leadership in healthcare. He has since held senior roles at Medtronic, where he led value-based care initiatives, and at Aetion, where he built partnerships that supported a major growth round. A frequent speaker at institutions including Harvard, MIT, and the G20, Christian is recognized for his ability to bridge science, business, and policy to expand access to transformative therapies.