Contribution of Fatigue to Cognitive Dysfunction in Childhood Acute Lymphoblastic Leukemia Survivors

Late effects such as neurocognitive issues and fatigue have been reported in childhood acute lymphoblastic leukemia (cALL) survivors. Yet, their association is often poorly understood. In this study, we wished to (1) describe neurocognitive difficulties and fatigue in a well-characterized cohort of long-term cALL survivors and (2) explore the risk of having neurocognitive deficits as a function of fatigue. Childhood ALL survivors (N = 285) from three Canadian treatment centers completed the DIVERGT battery of cognitive tests and the PedsQL Multidimensional Fatigue Scale. We performed logistic regressions to assess the risk of a survivor to show cognitive deficits (d = 0.35). The risk for cognitive deficits increased independently with levels of fatigue in the domains of cognitive speed and flexibility, working memory, and verbal fluency. For every 10-point increase on general or sleep/rest fatigue on the 0-100 scale, there was a median +23–35% risk of showing a deficit among the 7 tasks significantly associated with fatigue. Fatigue may constitute a complementary target when searching to mitigate cognitive issues in this population.儿童急性淋巴细胞白血病（childhood acute lymphoblastic leukemia, cALL）幸存者中已有研究报道存在神经认知障碍与疲劳等远期并发症，但二者间的关联机制迄今仍未得到充分阐明。本研究旨在达成两项研究目标：其一，对特征明确的长期cALL幸存者队列中的神经认知困难与疲劳症状进行系统性描述；其二，探讨疲劳程度与神经认知功能缺损发生风险的关联关系。本研究纳入来自加拿大3家治疗中心的285名儿童ALL幸存者，所有受试者均完成了DIVERGT认知测试组合与PedsQL多维疲劳量表的评估。本研究采用逻辑回归分析，以评估幸存者出现认知功能缺损的风险（效应量d=0.35）。结果显示，在认知速度与灵活性、工作记忆以及言语流畅性这几个认知维度中，认知功能缺损的发生风险随疲劳程度升高而独立上升。在0-100分的评分体系中，总体疲劳或睡眠/休息疲劳每升高10分，在与疲劳显著相关的7项测试任务中，受试者出现认知缺损的风险中位数升高23%~35%。针对该人群的认知问题进行干预时，疲劳或可成为一项补充干预靶点。