Heterogeneity of Alzheimer’s disease: consequence for drug trials?

Gayatri DeviEmail author View ORCID ID profile and
Philip Scheltens

Alzheimer's Research & Therapy201810:122

https://doi.org/10.1186/s13195-018-0455-y

Published: 19 December 2018

Abstract

Background

Alzheimer’s disease is a heterogenous disorder with multiple phenotypes and genotypes, although they eventually converge to a final common clinicopathological endpoint. However, Alzheimer’s disease drug trials do not account for the heterogeneity of the disease in trial design, impeding development of effective drugs.

Discussion

Alzheimer’s disease drug trials commonly have wide inclusion criteria that subsume multiple subtypes of the condition, with varying genotypes, phenotypes, and clinical courses. The outcome variables used in many trials may not be sensitive for the particular disease subtype and trials may not follow patients for the appropriate length of time necessary for the subtype of disease. Methods of stratifying treatment trial design to account for disease heterogeneity using algorithms incorporating demographics, neuroimaging, genetics, and clinical phenotypes, as well as more tailored outcome measures, are proposed to allow for personalized, precision medicine in Alzheimer’s disease therapeutics development.