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

Alzheimers Dement (Amst). 2024 Mar 7;16(1):e12563. doi: 10.1002/dad2.12563. eCollection 2024 Jan-Mar.

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.