Dye Nicholas B, Gondi Vinai, Mehta Minesh P
University of Maryland School of Medicine, Baltimore, MD, USA.
Northwestern Medicine Chicago Proton Center and CDH Brain Tumor Center, Warrenville, IL, USA.
Chin Clin Oncol. 2015 Jun;4(2):24. doi: 10.3978/j.issn.2304-3865.2015.05.05.
Cognitive decline, particularly in memory, is a side effect seen in patients with brain metastases and when severe, can have a significant impact on their quality of life. It is most often the result of multiple intersecting etiologic factors, including the use of whole brain radiation therapy, effects of which, in part, are mediated by damage within the hippocampus. A variety of clinical factors and comorbidities may impact the likelihood and severity of this cognitive decline, and affected patients should be considered for evaluation in a comprehensive neuro-rehabilitation or "brain fitness" program.
PREVENTION STRATEGIES OF NEUROCOGNITIVE DECLINE DUE TO WHOLE BRAIN RADIOTHERAPY (WBRT): Avoiding WBRT is warranted for some patients with brain metastases; particularly those <50 years old. However, when WBRT is clinically indicated, hippocampal avoidance WBRT (HA-WBRT) has been shown to significantly reduce memory decline compared to historical controls without compromising treatment efficacy. Additionally, the NMDA receptor antagonist memantine and renin-angiotensin-aldosterone system (RAAS) blockers have shown promise as neuroprotective agents that could be used prophylactically with radiation.
After the onset of neurocognitive decline the treatment is largely symptom-driven, however simply screening for and treating depression, fatigue, anxiety, cognitive slowing, and other processes may alleviate some impairment. Stimulants such as methylphenidate may be useful in treating symptoms of fatigue and cognitive slowing. Other treatments including donepezil and cognitive rehabilitation have been extensively tested in the population at risk for dementia, although they have not been adequately studied in patients following cranial radiotherapy. An innovative hypothetical approach is the use of intranasal metabolic stimulants such as low dose insulin, which could be valuable in improving cognition and memory, by reversing impaired brain metabolic activity.
Prevention of neurocognitive decline in patients with brain metastases requires a multimodal approach tailored to each patient's need, avoiding WBRT in some, altering the WBRT plan in others, and/or using neuroprotective prophylaxis in those in whom avoidance cannot be utilized. Likewise treatment will require a personalized combination of strategies optimized to address the patient's symptoms.
认知功能减退，尤其是记忆力减退，是脑转移瘤患者出现的一种副作用，严重时会对其生活质量产生重大影响。这通常是多种相互交织的病因所致，包括全脑放射治疗的使用，其部分影响是由海马体损伤介导的。多种临床因素和合并症可能会影响这种认知功能减退的可能性和严重程度，对于受影响的患者，应考虑在综合神经康复或“脑健康”项目中进行评估。
全脑放射治疗（WBRT）所致神经认知功能减退的预防策略：对于一些脑转移瘤患者，尤其是年龄小于50岁的患者，避免进行WBRT是有必要的。然而，当临床上有WBRT指征时，与既往未行海马体保护的全脑放射治疗（HA-WBRT）相比，海马体保护全脑放射治疗已被证明能显著减少记忆力减退，且不影响治疗效果。此外，N-甲基-D-天冬氨酸（NMDA）受体拮抗剂美金刚和肾素-血管紧张素-醛固酮系统（RAAS）阻滞剂已显示出有望作为神经保护剂，可与放疗联合预防性使用。
神经认知功能减退发生后，治疗主要以症状为导向，然而，简单地筛查和治疗抑郁、疲劳、焦虑、认知迟缓及其他症状可能会减轻一些损害。哌甲酯等兴奋剂可能有助于治疗疲劳和认知迟缓症状。其他治疗方法，包括多奈哌齐和认知康复，已在痴呆风险人群中进行了广泛测试，尽管它们在颅脑放疗后的患者中尚未得到充分研究。一种创新的假设方法是使用鼻内代谢兴奋剂（如低剂量胰岛素），通过逆转受损的脑代谢活动，这可能对改善认知和记忆有价值。
预防脑转移瘤患者的神经认知功能减退需要一种根据每个患者需求定制的多模式方法，一些患者避免进行WBRT，另一些患者改变WBRT计划，和/或对无法避免WBRT的患者使用神经保护预防措施。同样，治疗将需要个性化的策略组合，以优化解决患者的症状。
