Supplementary Material for: Calibrating Longitudinal Cognition in Alzheimer's Disease Across Diverse Test Batteries and Datasets

Background: We sought to identify optimal approaches by calibrating longitudinal cognitive performance across studies with different neuropsychological batteries. Methods: We examined four approaches to calibrate cognitive performance in nine longitudinal studies of Alzheimer's disease (AD) (n = 10,875): (1) common test, (2) standardize and average available tests, (3) confirmatory factor analysis (CFA) with continuous indicators, and (4) CFA with categorical indicators. To compare precision, we determined the minimum sample sizes needed to detect 25% cognitive decline with 80% power. To compare criterion validity, we correlated cognitive change from each approach with 6-year changes in average cortical thickness and hippocampal volume using available MRI data from the AD Neuroimaging Initiative. Results: CFA with categorical indicators required the smallest sample size to detect 25% cognitive decline with 80% power (n = 232) compared to common test (n = 277), standardize-and-average (n = 291), and CFA with continuous indicators (n = 315) approaches. Associations with changes in biomarkers changes were the strongest for CFA with categorical indicators. Conclusions: CFA with categorical indicators demonstrated greater power to detect change and superior criterion validity compared to other approaches. It has wide applicability to directly compare cognitive performance across studies, making it a good way to obtain operational phenotypes for genetic analyses of cognitive decline among people with AD.**背景**：本研究旨在通过对采用不同神经心理学测验组合的多项纵向研究中的认知表现进行校准，以确定最优的认知表现校正方法。 **方法**：本研究针对9项阿尔茨海默病（Alzheimer's Disease, AD）纵向研究（总样本量n=10875），评估了4种认知表现校准方法：(1) 通用测验法；(2) 标准化并平均现有测验得分法；(3) 基于连续指标的验证性因子分析（Confirmatory Factor Analysis, CFA）法；(4) 基于分类指标的验证性因子分析法。为比较各方法的精度，我们计算了在检验效能为80%的条件下，检测25%认知下降所需的最小样本量；为比较效标效度，我们利用阿尔茨海默病神经影像倡议（Alzheimer's Disease Neuroimaging Initiative, ADNI）的现有MRI数据，将每种方法得到的认知变化与平均皮层厚度和海马体积的6年变化进行相关性分析。 **结果**：与通用测验法（n=277）、标准化平均法（n=291）及基于连续指标的验证性因子分析法（n=315）相比，基于分类指标的验证性因子分析法在检验效能为80%时检测25%认知下降所需的最小样本量最小（n=232）；且该方法与生物标志物变化的关联强度最高。 **结论**：相较于其他方法，基于分类指标的验证性因子分析法具备更强的变化检测效能与更优的效标效度。该方法可直接跨研究比较认知表现，适用范围广泛，是获取阿尔茨海默病患者认知下降遗传分析所需操作表型的理想途径。