Supplementary Material for: A Methodological Perspective on the Longitudinal Cognitive Change after Stroke

<b><i>Background/Aims:</i></b> Most studies of poststroke cognitive impairment (PSCI) have analyzed cognitive levels at specific time points rather than their changes over time. Furthermore, they seldom consider correlations between cognitive domains. We aimed to investigate the effects of these methodological considerations on determining significant PSCI predictors in a longitudinal stroke cohort. <b><i>Methods:</i></b> In patients who underwent neuropsychological tests at least twice after stroke, we adopted a multilevel hierarchical mixed-effects model with domain-specific cognitive changes and a multivariate model for multiple outcomes to reflect their correlations. <b><i>Results:</i></b> We enrolled 375 patients (median follow-up of 34.1 months). Known predictors of PSCI were generally associated with cognitive levels; however, most of the statistical significances disappeared when cognitive changes were set as outcomes, except age for memory, prior stroke and baseline cognition for executive/attention domain, and baseline cognition for visuospatial function. The multivariate analysis which considered multiple outcomes simultaneously further altered these associations. <b><i>Conclusions:</i></b> This study shows that defining outcomes as changes over time and reflecting correlations between outcomes may affect the identification of predictors of PSCI.

背景与目的：既往针对卒中后认知障碍（poststroke cognitive impairment, PSCI）的相关研究，大多仅分析特定时间节点的认知水平，而非认知功能随时间的动态变化；且极少考量不同认知域之间的相关性。本研究旨在探究上述两类方法学因素，在纵向卒中队列中筛选具有统计学意义的PSCI预测因子时所产生的影响。
方法：本研究纳入卒中后至少完成两次神经心理学测评的患者，采用针对认知域特异性变化的多层分级混合效应模型，以及适配多结局变量的多元分析模型，以体现认知域间的相关性。
结果：本研究共纳入375例患者，中位随访时长为34.1个月。既往已明确的PSCI预测因子大多与基线认知水平存在关联；但当以认知变化作为结局变量时，多数预测因子的统计学显著性消失，仅存例外：年龄与记忆域相关，既往卒中史、基线认知水平与执行/注意域相关，基线认知水平与视空间功能域相关。同时纳入多结局变量的多元分析进一步改变了上述关联模式。
结论：本研究证实，将结局变量定义为随时间的认知变化，并考量结局变量间的相关性，可能会对PSCI预测因子的筛选结果产生影响。