Novel digital biomarker identification in Alzheimer’s Disease and related dementias

Abstract

AbstractBackgroundThe gold standard method for assessing the efficacy of dementia treatments, the Alzheimer’s Disease (AD) Assessment Scale‐Cognitive Subscale (ADAS‐Cog), has limitations of use based on the level of cognitive decline of a patient, the need for an in‐person evaluation, and the sampling of a time point in the patient experience. However, measuring factors associated with patient disease progression is key to not only assessing treatment efficacy, but also to predicting patient trajectory. New measures are needed to fill the gaps associated with the ADAS‐Cog, and digital tools are poised to reveal novel biomarkers of AD and related dementias (ADRD) with the added benefit of continuous measurements in a real‐world setting that give voice to patients unable to directly communicate experiences.MethodA systematic literature review conducted globally of over two million publications is used to identify meaningful aspects of health and physiological characteristics of ADRD. In‐person interviews of patients, caregivers, clinicians, and scientists (n = 50) supplement the findings of the review and, taken together in a mixed methods approach, allow for the creation and dissemination of a survey of the larger ADRD population (n = 2500) regarding the clinical and patient‐centric value of potential measures.ResultPrevious efforts led to the creation of a database of over 300 digital endpoints used in previous and ongoing trials, including several related to ADRD and cognition (i.e., blink count, activity, acoustic/linguistic measures). The resulting list of candidate biomarkers from the mixed methods study is assessed for feasibility of digital measurement, cultural inclusivity, clinical relevance, and accuracy of representation of patient lived experience to produce an optimized set of digital biomarkers defining a meaningful aspect of health in ADRD.ConclusionDigital biomarker measurement, particularly in ADRD, allows for a richer, more comprehensive understanding of the patient’s lived experience, the patient’s disease progression, and the efficacy of treatments. Capturing novel digital biomarkers continuously and in a real‐world setting provides patients, caregivers, and clinicians with useful insights absent of the limitations associated with the ADAS‐Cog. This digital approach further lays the foundation for the development of patient‐centric measures acceptable to clinicians, regulators, and payers.