@article{a9105964a00a4d3bbe525405e0d4910e,
title = "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 = "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.",
author = "Asaad Baksh and Andre Strydom and Isabelle Carri{\`e}re and Ben Carter and Karen Ritchie",
note = "Funding Information: The authors thank all the participants in this study for their time. We would like to thank Dr Rosalyn Hithersay for her Emax modelling work in people with Down syndrome. R. Asaad Baksh was supported by a J{\'e}r{\^o}me Lejeune Foundation postdoctoral research fellowship. Andr{\'e} Strydom received funding from the Medical Research Council grant MR/S011277/1, MR/ S005145/1, and MR/R024901/1; European Commission (H2020 SC1 Gene overdosage and comorbidities during the early lifetime in Down Syndrome GO- DS21- 848077); J{\'e}r{\^o}me Lejeune Foundation. Funding Information: The authors thank all the participants in this study for their time. We would like to thank Dr Rosalyn Hithersay for her Emax modelling work in people with Down syndrome. R. Asaad Baksh was supported by a J{\'e}r{\^o}me Lejeune Foundation postdoctoral research fellowship. Andr{\'e} Strydom received funding from the Medical Research Council grant MR/S011277/1, MR/ S005145/1, and MR/R024901/1; European Commission (H2020 SC1 Gene overdosage and comorbidities during the early lifetime in Down Syndrome GO‐ DS21‐ 848077); J{\'e}r{\^o}me Lejeune Foundation. Publisher Copyright: {\textcopyright} 2024 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",
year = "2024",
month = mar,
day = "7",
doi = "10.1002/dad2.12563",
language = "English",
volume = "16",
journal = "Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring",
issn = "2352-8729",
publisher = "Elsevier BV",
number = "1",
}