Pathways to personalized medicine—Embracing heterogeneity for progress in clinical therapeutics research in Alzheimer's disease.

Biological and clinical heterogeneity is a major challenge in research for developing new treatments for Alzheimer's disease (AD). AD may be defined by its amyloid beta and tau pathologies, but we recognize that mixed pathologies are common, and that diverse genetics, central nervous system (CNS) and systemic pathophysiological processes, and environmental/experiential factors contribute to AD's diverse clinical and neuropathological features. All these factors are rational targets for therapeutic development; indeed, there are hundreds of candidate pharmacological, dietary, neurostimulation, and lifestyle interventions that show benefits in homogeneous laboratory models. Conventional clinical trial designs accommodate heterogeneity poorly, and this may be one reason that progress in translating candidate interventions has been so difficult. We review the challenges of AD's heterogeneity for the clinical trials enterprise. We then discuss how advances in repeatable biomarkers and digital phenotyping enable novel "single‐case" and adaptive trial designs to accelerate therapeutics development, moving us closer to personalized research and medicine for AD. Highlights: Alzheimer's disease is diverse in its clinical features, course, risks, and biology.Typical randomized controlled trials are exclusive and necessarily large to attain arm comparability with broad outcomes.Repeated blood biomarkers and digital tracking can improve outcome measure precision and sensitivity.This enables the use of novel "single‐case" and adaptive trial designs for inclusivity, rigor, and efficiency. [ABSTRACT FROM AUTHOR]

Copyright of Alzheimer's & Dementia: The Journal of the Alzheimer's Association is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)