Kang Kaidi, Zhang Panpan, Dumitrescu Logan, Mukherjee Shubhabrata, Lee Michael L, Choi Seo-Eun, Trittschuh Emily H, Mez Jesse, Saykin Andrew J, Gifford Katherine A, Buckley Rachel F, Gao Xiaoting, Di Jianing, Crane Paul K, Hohman Timothy J, Liu Dandan
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Vanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Alzheimers Dement. 2025 Jun;21(6):e70335. doi: 10.1002/alz.70335.
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.
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.
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.
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.
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.
准确评估阿尔茨海默病（AD）多个领域认知衰退的时间顺序至关重要。现有文献呈现出有争议的结论，这可能是由于使用了单一队列和不同的分析策略。
使用了阿尔茨海默病测序项目表型协调联盟（ADSP-PHC）中13个队列在记忆、语言和执行功能方面的协调综合认知测量指标。以发生AD诊断的时间为时间尺度，开发了一种基于双锚定事件的S形混合模型。
总体而言，记忆衰退先于语言衰退，随后是执行功能衰退。这种时间顺序在载脂蛋白E ε4携带者状态、性别和种族/民族的每个亚组中通常都持续存在。
本研究展示了使用多个队列的协调数据来描述AD进展过程中认知衰退的时间顺序。以发生AD诊断的时间为时间尺度可以提高研究的可重复性和临床实践水平。
阿尔茨海默病测序项目表型协调联盟对13项队列研究的协调综合认知测量指标，采用一种基于双锚定事件的新型S形混合模型进行拟合，揭示了AD进展过程中认知衰退的以下时间顺序：记忆、语言和执行功能。如果仅使用单个队列研究进行调查，由于研究之间潜在的异质性，认知衰退的时间顺序会有所不同。这种时间顺序在载脂蛋白E ε4携带者状态、性别和种族/民族的每个亚组中通常都持续存在。
