Utz Kathrin S, Lee De-Hyung, Lämmer Alexandra, Waschbisch Anne, Linker Ralf A, Schenk Thomas
Department of Neurology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Department of Psychology, Ludwig-Maximilians-Universität München, Leopoldstr. 13, 80802 München, Germany.
Ther Adv Neurol Disord. 2016 Jul;9(4):269-80. doi: 10.1177/1756285616643892. Epub 2016 Apr 18.
Disease-modifying therapies (DMTs) are applied to delay or prevent disease progression in multiple sclerosis (MS). While this has mostly been proven for physical symptoms, available studies regarding long-term effects of DMTs on cognitive functions are rare and sometimes inconsistent due to methodological shortcomings. Particularly in the case of fingolimod, comprehensive data on cognitive functions are not yet available. Therefore, we set out to reliably assess cognitive functions in patients with relapsing-remitting MS (RRMS) treated with DMTs over 1 year.
Cognitive functions were assessed with eight tests at three timepoints: baseline, 6-month follow up and 12-month follow up. First, we investigated whether the stability of cognitive functions (i.e. not falling below the 5% cut-off in more than one test) over 1 year in RRMS patients (n = 41) corresponds to the stability in healthy individuals (n = 40) of a previous study. Second, we compared the percentage of declined and improved patients in the different tests. Third, we compared patients treated with fingolimod (n = 22) with patients treated with natalizumab (n = 11) with regard to cognitive stability. Fourth, based on the patient data, the Reliable Change Index was applied to compute cut-offs for reliable cognitive change.
Approximately 75% of RRMS patients treated with DMTs remained stable over the course of 1 year. The Paced Auditory Serial Addition Test (PASAT) and the Spatial Recall Test (SPART), produced improvements in 12.5% and 30.6%, respectively, probably due to practice effects. Patients treated with fingolimod did not differ from patients treated with natalizumab with regard to cognitive stability.
Cognitive functions remain relatively stable under DMT treatment over 1 year, irrespective of the type of medication. Furthermore, the tests PASAT and SPART should be interpreted cautiously in studies examining performance changes over time. The provided RCI norms may help clinicians to determine whether a difference in two measurements observed in a RRMS patient is reliable.
疾病修饰治疗（DMTs）用于延缓或预防多发性硬化症（MS）的疾病进展。虽然这在很大程度上已被证明对身体症状有效，但关于DMTs对认知功能长期影响的现有研究很少，且由于方法学缺陷有时并不一致。特别是对于芬戈莫德，关于认知功能的全面数据尚未可得。因此，我们着手可靠地评估接受DMTs治疗超过1年的复发缓解型多发性硬化症（RRMS）患者的认知功能。
在三个时间点用八项测试评估认知功能：基线、6个月随访和12个月随访。首先，我们调查RRMS患者（n = 41）认知功能在1年中的稳定性（即不止一项测试不低于5%的临界值）是否与先前一项研究中健康个体（n = 40）的稳定性相符。其次，我们比较不同测试中认知功能下降和改善患者的百分比。第三，我们比较接受芬戈莫德治疗的患者（n = 22）和接受那他珠单抗治疗的患者（n = 11）在认知稳定性方面的情况。第四，基于患者数据，应用可靠变化指数来计算可靠认知变化的临界值。
接受DMTs治疗的RRMS患者中约75%在1年期间保持稳定。听觉连续加法测试（PASAT）和空间回忆测试（SPART）分别有12.5%和30.6%的改善，可能是由于练习效应。接受芬戈莫德治疗的患者与接受那他珠单抗治疗的患者在认知稳定性方面没有差异。
在DMT治疗1年期间，无论药物类型如何，认知功能都保持相对稳定。此外，在研究随时间的表现变化时，对PASAT和SPART测试的结果应谨慎解读。提供的RCI规范可能有助于临床医生确定在RRMS患者中观察到的两次测量之间的差异是否可靠。
