Antiepileptic drug effects on subjective and objective cognition
Antiepileptic drug effects on subjective and objective cognition
复制标题
DOI：
10.1016/j.yebeh.2020.106906
复制
发表时间：
2020-03-01
影响因子：
2.6
通讯作者：
Jobst, Barbara C.
中科院分区：
文献类型：
--
作者：
Quon, Robert J.;Mazanec, Morgan T.;Jobst, Barbara C.
理论基础：认知障碍是癫痫(PWE)患者最常见的症状之一。这些损害不仅与癫痫发作有关，而且经常被报告为抗癫痫药物(AED)的不良反应。以前的研究已经考察了AED单一疗法和综合疗法的认知效果，但关于这些差异的主观和客观认知方面的研究有限。目前的研究使用了由疾病控制和预防中心(CDC)赞助的癫痫良好管理网络(MEW)合作进行的先前研究的数据。我们使用了三个不同的档案数据集：(1)达特茅斯-希区柯克医学中心的HOBSCOTCH疗效试验(HOB-1)，(2)多点复制试验(HOB-2)，以及(3)在纽约大学医学院进行的癫痫自我管理研究。方法：这项回顾分析结合了来自三个数据集的基线数据，以确定抗癫痫药物的数量和类型与主观(患者报告的)和客观(检验者评估的)认知之间的关系。主观认知使用三个数据集(n=224)中的生活质量问卷(QOLIE-31)，而客观认知使用HOB-1数据集中的神经心理状态评估重复组合(RBANS)(n=65)和HOB-2数据集中的成人电话认知简明测试(BTACT)(n=91)。我们的初始评估使用了多变量线性回归，然后是倾向得分匹配，以提供对协变量的更强控制。配对是基于显著不同的协变量，如教育、抑郁和既往癫痫手术史。结果：在接受综合治疗(2+AED)的患者中，主观认知损害明显比接受单一治疗(1个AED)的患者更严重(调整后p=0.041)。这些发现与我们的倾向分数匹配的单一疗法和综合疗法的比较是一致的，这表明综合疗法除了在RBANS(总分p=0.05)和BTACT的特定子域(情景言语记忆p<；0.01，工作记忆p<；0.01，加工速度p<；0.01)上的损害外，总体主观认知能力较差(调整后p=0.01)。有趣的是，老一辈的AED比新一代和联合治疗的AED有更好的语言表现(RBANS语言p=0.03)。在控制了托吡酯和唑尼沙胺的影响后，这些特定语言的发现仍然显著(p=0.04)。结论：更多的AED与PWE的主客观认知显著负相关，与先前的研究一致。抗癫痫药物类型本身似乎与主观认知无关。我们的发现表明，无效的AEDs应该被替换，而不是在治疗方案中引入额外的AEDs。此外，虽然主观和客观认知评估都敏感地检测基于AED状态的差异，但神经心理学客观亚域提供了关于AED如何损害认知的额外和具体的见解。(C)2020 Elsevier Inc.保留所有权利。
Rationale: Cognitive impairment is one of the most common complaints for persons with epilepsy (PWE). These impairments are not only associated with seizures, but are also regularly reported as adverse effects of antiepileptic drugs (AEDs). Previous studies have examined cognitive effects of both AED monotherapy and polytherapy, yet there is limited research on these differences with respect to both subjective and objective cognition. The current study uses data from previous research conducted by the Centers for Disease Control and Prevention (CDC)-sponsored Managing Epilepsy Well (MEW) Network collaborative. We used three distinct archival datasets from the following: (1) the HOBSCOTCH efficacy trial at Dartmouth-Hitchcock Medical Center (HOB-1), (2) the multisite replication trial (HOB-2), and (3) epilepsy self-management research conducted at the NYU School of Medicine.Methods: This retrospective analysis combined baseline data from three datasets to determine how the number of AEDs and the type of AEDs were associated with subjective (patient-reported) and objective (examiner-assessed) cognition. Subjective cognition was captured using the cognitive subscale of the Quality of Life in Epilepsy Inventory (QOLIE-31) in all three datasets (n = 224), while objective cognition was measured using the Repeated Battery for the Assessment of Neuropsychological Status (RBANS) in the HOB-1 dataset (n = 65) and the Brief Test of Adult Cognition by Telephone (BTACT) in the HOB-2 dataset (n = 91). Multivariable linear regression was utilized for our initial assessments, followed by propensity score matching to provide stronger control of covariates. Matching was based on significantly different covariates, such as education, depression, and history of prior epilepsy surgery. Nonparametric statistical tests were utilized to compare these matched subjects.Results: Subjective cognitive impairment was significantly worse among individuals on polytherapy (2 + AEDs) compared with those on monotherapy (1 AED) (adjusted p = 0.041). These findings were consistent with our propensity score matched comparison of monotherapy and polytherapy, which indicated that polytherapy was associated with worse overall subjective cognition (adjusted p = 0.01), in addition to impairments on the RBANS (Total score p = 0.05) and specific subdomains of the BTACT (Episodic Verbal Memory p < 0.01, Working Memory p < 0.01, Processing Speed p < 0.01). Interestingly, older generation AEDs were associated with better language performance than newer generation and combined generation AED therapy (RBANS Language p = 0.03). These language-specific findings remained significant after controlling for the effects of topiramate and zonisamide (p = 0.04).Conclusions: A greater number of AEDs is significantly and negatively associated with subjective and objective cognition in PWE, and is in line with previous research. Antiepileptic drug type did not, in itself, appear to be associated with subjective cognition. Our findings suggest that ineffective AEDs should be replaced, rather than introducing additional AEDs to a treatment regimen. Further, while subjective and objective cognition assessments were both sensitive at detecting differences based on AED status, the neuropsychological objective subdomains offer additional and specific insights into how cognition is impaired with AEDs. (C) 2020 Elsevier Inc. All rights reserved.