Toward the right treatment at the right time: Modeling the trajectory of cognitive decline to identify the earliest age of change in people with Alzheimer's disease

Abstract

Abstract Introduction Age is the greatest risk factor for Alzheimer's disease (AD). A limitation of randomized control trials in AD is a lack of specificity in the age ranges of participants who are enrolled in studies of disease‐modifying therapies. We aimed to apply Emax (i.e., maximum effect) modeling as a novel approach to identity ideal treatment windows. Methods Emax curves were fitted to longitudinal cognitive data of 101 participants with AD and 1392 healthy controls. We included the Mini‐Mental State Examination (MMSE) and tests of verbal fluency and executive functioning. Results In people with AD, the earliest decline in the MMSE could be detected in the 67–71 age band while verbal fluency declined from the 41–45 age band. In healthy controls, changes in cognition showed a later trajectory of decline. Discussion Emax modeling could be used to design more efficient trials which has implications for randomized control trials targeting the earlier stages of AD.