Kaidi Kang, Panpan Zhang, Logan Dumitrescu, Shubhabrata Mukherjee, Michael L. Lee, Seo-Eun Choi, Emily H. Trittschuh, Jesse Mez, Andrew J. Saykin, Katherine A. Gifford, Rachel F. Buckley, Xiaoting Gao, Jianing Di, Paul K. Crane, Timothy J. Hohman, Dandan Liu
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Abstract
INTRODUCTION
Accurately assessing the temporal order of cognitive decline across multiple domains is critical in Alzheimer's disease (AD). Existing literature presents 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 Alzheimer's Disease Sequencing Project Phenotype Harmonization Consortium (ADSP-PHC) were used. A double anchoring events–based sigmoidal mixed model was developed using time to incident AD diagnosis as the time scale.
RESULTS
In general, decline in memory occurred before decline in language, followed by decline in executive function. This temporal order generally persisted within each subgroup of apolipoprotein E ε4 carrier status, sex, and race/ethnicity.
DISCUSSION
This study demonstrated the use of harmonized data across multiple cohorts to characterize the temporal order of cognitive decline along AD progression. Using time to incident AD diagnosis as the time scale can enhance research reproducibility and clinical practice.
Highlights
Alzheimer's Disease Sequencing Project Phenotype Harmonization Consortium's harmonized composite cognitive measures from 13 cohort studies fitted with a novel double anchoring event-based sigmoidal mixed model reveal the following temporal order of cognitive decline toward AD progression: memory, language, and executive function.
If only investigated using individual cohort studies, the temporal order of cognitive decline would vary due to the underlying heterogeneities across studies.
This temporal order generally persisted within each subgroup of apolipoprotein E ε4 carrier status, sex, and race/ethnicity.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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