Supplementary Material for: Apathy Secondary to Stroke: A Systematic Review and Meta-Analysis

<strong><em>Background:</em></strong> Apathy is a disturbance of motivation, frequent in survivors of stroke. Several studies have evaluated the rate of apathy secondary to stroke and risk factors. Different conclusions and contradictory findings have been published. We aimed to perform a systematic review and meta-analysis of all studies evaluating apathy secondary to stroke to better estimate its rate and risk factors, and explore associations with poorer outcomes. <b><i>Methods:</i></b> We searched PubMed, Cochrane Library, PsychINFO and PsycBITE databases and screened references of included studies and review articles for additional citations. Search results and data extraction was performed independently. We systematically reviewed available publications reporting investigations on ischemic and intracerebral hemorrhagic stroke and apathy. Quality assessment of the studies was performed independently. Subgroup analyses were performed according to stroke phase (acute and post-acute), stroke past history (first-ever and any-stroke) and patient age (younger and older patients). Pooled odds ratios (OR) and standardized mean difference, and 95% confidence intervals (CI), were derived by random-effects meta-analysis. Heterogeneity was assessed with I² test. <b><i>Results:</i></b> From the initial 1,399 publications, we included 19 studies (2,221 patients). The pooled rate of apathy was 36.3% (95% CI 30.3–42.8; I² = 46.8), which was similar for acute [39.5% (95% CI 28.9–51.1)] and post-acute phase [34.3% (95% CI 27.8–41.4)], and about three times higher than the rate of depression [12.1% (95% CI 8.2–17.3)]. Apathetic patients were on average 2.74 years older (95% CI 1.25–4.23; I² = 0%). No gender differences were found. Depression (OR 2.29; 95% CI 1.41–3.72; I² = 44%) and cognitive impairment (OR 2.90; 95% CI 1.09–7.72; I² = 14%) were more frequent and severe in apathetic patients. Apathy rate was similar for ischemic and hemorrhagic stroke type and for left- and right-sided hemispheric lesions. Clinical global outcome was similar between apathetic and nonapathetic patients. <b><i>Conclusion:</i></b> Apathy secondary to stroke is a more frequent neuropsychiatric disturbance than depression. Apathetic patients are more frequently and severely depressed and cognitively impaired. A negative impact of apathy secondary to stroke on clinical global outcome cannot be ascribed. Future research should properly address its predictor factors and evaluate the impact of apathy treatment options in stroke patients.

<strong><em>背景：</em></strong> 情感淡漠（apathy）是一种动机障碍，在脑卒中（stroke）幸存者中较为常见。既往已有多项研究对脑卒中继发情感淡漠的发生率及其危险因素展开评估，但相关结论存在分歧，研究结果亦存在矛盾。本研究旨在针对所有评估脑卒中继发情感淡漠的研究开展系统综述与荟萃分析，以更精准地估算其发生率与危险因素，并探讨其与不良预后的关联。<strong><i>方法：</i></strong> 我们检索了PubMed、Cochrane图书馆、PsychINFO及PsycBITE数据库，并筛查纳入研究与综述文章的参考文献以获取额外引用文献。检索流程与数据提取均由两名研究者独立完成。我们系统回顾了所有报道缺血性脑卒中、脑内出血性脑卒中与情感淡漠相关研究的已发表文献。研究质量评估亦独立开展。亚组分析依据脑卒中分期（急性期与亚急性期）、脑卒中既往史（首次发作与既往发作）及患者年龄（年轻与年长患者）进行。采用随机效应荟萃分析计算合并比值比（OR）、标准化均数差及95%置信区间（CI）。异质性检验采用I²检验。<strong><i>结果：</i></strong> 初始检索共得到1399篇文献，最终纳入19项研究，涉及2221名患者。合并后的情感淡漠发生率为36.3%（95%CI 30.3~42.8；I²=46.8），急性期[39.5%（95%CI 28.9~51.1）]与亚急性期[34.3%（95%CI 27.8~41.4）]的发生率无显著差异，且约为抑郁症发生率（12.1%，95%CI 8.2~17.3）的三倍。情感淡漠患者的平均年龄较无淡漠者高2.74岁（95%CI 1.25~4.23；I²=0%），未发现性别相关差异。情感淡漠患者更常出现抑郁症状（OR=2.29；95%CI 1.41~3.72；I²=44%）与认知功能损害（OR=2.90；95%CI 1.09~7.72；I²=14%），且症状更为严重。缺血性与出血性脑卒中患者的情感淡漠发生率无显著差异，左侧与右侧半球病灶患者的发生率亦无明显区别。情感淡漠组与非淡漠组患者的临床总体预后无显著差异。<strong><i>结论：</i></strong> 脑卒中继发的情感淡漠是一种较抑郁症更为常见的神经精神障碍。情感淡漠患者更易出现抑郁症状与认知功能损害，且症状程度更重。目前尚无法确认脑卒中继发情感淡漠会对临床总体预后产生负面影响。未来的研究应明确其预测因素，并评估针对脑卒中患者的情感淡漠治疗方案的效果。