The Dynamics of Cognitive Decline towards Alzheimer’s Disease Progression: Results from ADSP-PHC’s Harmonized Cognitive Composites

Abstract

Introduction: Accurately assessing temporal order of cognitive decline across multiple domains is critical in Alzheimer's disease (AD). Existing literature presented controversial conclusions likely due to the use of a single cohort and different analytical strategies.

Methods: Harmonized composite cognitive measures in memory, language and executive functions from 13 cohorts in the ADSP-PHC data are used. A novel double anchoring events-based sigmoidal mixed model was developed using time to the incident of AD diagnosis as the time scale.

Results: Decline in memory occurred before decline in language which was followed by the decline in executive function. Throughout the entire AD continuum, APOE-ε4 non-carriers and non-Hispanic Whites showed better memory performance, respectively, in all three cognitive domains.

Discussion: Using harmonized data across multiple cohorts is the key to accurately characterizing the temporal order of AD biomarkers. Time to incident AD diagnosis should be used as the time scale for reproducibility purposes.