A Framework for Patient Stratification in Clinical Trials for Alzheimer’s Disease Henry C Cousins1 and Clara C Cousins2*

Abstract

Drug discovery efforts in Alzheimer’s disease depend increasingly

Perspectives and challenges in patient stratification in Alzheimer’s disease

“…Stratifying patients by those who may likely benefit from a DMT, according to current clinical thinking, will be crucial for understanding the prognosis for defined patient subgroups [ 21 ]. In recent years, investigation of DMTs has focused on slowing disease progression and targeting early (i.e., prodromal-to-mild) AD [ 5 ]; accordingly, patients are stratified for earlier stages of disease [ 10 ]. The Free and Cued Selective Reminding Test (FCSRT) is a neuropsychological test used to evaluate episodic memory and can be used to enrich a clinical trial population [ 40 , 42 ].…”

“…These putative DMTs mainly target disease onset or disease progression in the earlier stages of AD. A robust patient stratification scheme will work to exclude people who are ineligible for DMTs based on a combination of cognitive and functional assessments, genetic risk factors, demographic and lifestyle factors, and AD pathology [ 10 ].…”

“…This makes it difficult to determine the appropriate clinical course of action, as people may exhibit multiple phenotypes on distinct disease trajectories [ 8 , 9 ]. Patient stratification is an approach that aims to cluster people with a disease into more homogeneous groups by classifying them according to factors considered highly important to the disease [ 10 ], so that interventions can be offered to those who will benefit the most. Proposed patient stratification schemes in AD have focused on those that can account for differing contributions from all relevant risk factors, such as genetic predisposition, molecular indicators, and pathologic stage disease [ 10 ].…”

“…Patient stratification is an approach that aims to cluster people with a disease into more homogeneous groups by classifying them according to factors considered highly important to the disease [ 10 ], so that interventions can be offered to those who will benefit the most. Proposed patient stratification schemes in AD have focused on those that can account for differing contributions from all relevant risk factors, such as genetic predisposition, molecular indicators, and pathologic stage disease [ 10 ]. A patient stratification scheme may account for molecular indicators, pathologic staging, and relevant risk factors including genetic predisposition [ 10 ].…”

“…Proposed patient stratification schemes in AD have focused on those that can account for differing contributions from all relevant risk factors, such as genetic predisposition, molecular indicators, and pathologic stage disease [ 10 ]. A patient stratification scheme may account for molecular indicators, pathologic staging, and relevant risk factors including genetic predisposition [ 10 ]. Official bodies such as the World Health Organization have recognized that the stratification of the health risks of people with chronic diseases could strengthen population health management and enable the provision of better-tailored services [ 11 ].…”