Effect and Mechanism of Acupuncture for Cancer-related Cognitive Impairment (ENHANCE)

项目总结 癌症相关认知障碍(CRCI)是一种毁灭性的疾病，影响到四分之三的乳腺癌幸存者。 非药物干预(如运动、认知训练)显示了CRCI的初步效果， 但它们的具体效果还需要在使用主动/注意力控制的更大规模、严格的试验中得到证实。更多 重要的是，考虑到CRCI的病因和表现是多方面的，单一的治疗方法不太可能是 因此，仍然迫切需要测试新的干预措施和个性化治疗。 针灸在癌症症状管理方面的证据越来越多，但它在治疗CRCI方面的作用 目前仍不清楚。在动物模型中，针刺已被证明可以调节海马区 脑源性神经营养因子是一种重要的认知生物标志物。一项中国研究(N=80)发现 针刺改善乳腺癌患者认知功能与升高血清脑源性神经营养因子的比较 常规护理，但由于样本量小和缺乏假对照，结果受到限制，因此排除了 对特定疗效的评价。在我们最近的比较有效性试验(N=160)的二次分析中 针灸与认知行为疗法治疗失眠(CBT-I)相比，针灸显著改善 主观失眠以及感知和客观的认知功能，表明目标睡眠 改善认知能力。针刺也显著增加了血清BDNF，尤其是在那些低 基线水平，而CBT-I没有。这表明BDNF是一种特定的机制，通过它可以 针灸会影响认知，并有助于识别最有可能对针灸做出反应的个体， 从而使治疗个人化。基于这些数据，我们的中心假设是针灸是一种有效的 CRCI的治疗通过脑源性神经营养因子和睡眠的机制发挥作用。在这项工作的基础上，我们带来 联合多学科团队提出针灸治疗癌症的作用和机制 认知障碍(增强)试验。我们发现，近80%患有CRCI的乳腺癌幸存者报告说 失眠，呼应了越来越多关于认知和睡眠之间联系的研究。因此，我们将招聘260人 患有CRCI和失眠的乳腺癌幸存者，在随机对照试验中将他们随机分为3种情况之一：1) 针灸，2)假针灸(SA)，或3)常规护理等待名单对照(WLC)。我们将收集血清中的BDNF 以及从基线到第26周的患者报告的/客观的认知和睡眠测量。具体目标 1)确定针刺对知觉CRCI和客观认知功能的影响；2)确定针刺对感知CRCI和客观认知功能的影响 通过脑源性神经营养因子评价针刺对认知CRCI和客观认知功能的作用机制 目的：阐明失眠对认知CRCI和客观认知功能在针灸治疗中的作用。 如果成功，我们的研究将扩大CRCI的治疗选择，促进对 针灸，理清睡眠与认知的关系，有助于转变治疗方法 基于脑源性神经营养因子特征和失眠的针对CRCI表型的个性化模型。

PROJECT SUMMARY Cancer-related cognitive impairment (CRCI) is a devastating condition, affecting 3 in 4 breast cancer survivors. Non-pharmacologic interventions (e.g. exercise, cognitive training) demonstrated preliminary effects for CRCI, but their specific efficacies need to be confirmed in larger, rigorous trials using active/attention controls. More importantly, given the multi-faceted etiology and presentation of CRCI, it is unlikely that a single therapy is optimal for all patients; thus, there remains a critical need to test novel interventions and personalize treatment. Acupuncture has a growing evidence base in cancer symptom management, but its role in treating CRCI remains unclear. In animal models, acupuncture has been shown to modulate hippocampal expression of brain-derived neurotrophic factor (BDNF), an important cognitive biomarker. A Chinese study (N=80) found that acupuncture improved cognitive function and increased serum BDNF in breast cancer patients compared to usual care, but findings were limited by small sample size and lack of sham control, thus precluding evaluation of specific efficacy. In secondary analyses of our recent comparative effectiveness trial (N=160) of acupuncture versus cognitive-behavioral therapy for insomnia (CBT-I), acupuncture significantly improved subjective insomnia as well as perceived and objective cognitive functions, suggesting that targeting sleep improves cognition. Acupuncture also significantly increased serum BDNF, particularly among those with low baseline levels, whereas CBT-I did not. This suggests that BDNF is a specific mechanism by which acupuncture influences cognition and could help to identify individuals most likely to respond to acupuncture, thereby personalizing therapy. Based on this data, our central hypothesis is that acupuncture is an efficacious treatment for CRCI that works through a mechanism involving BDNF and sleep. Building on this work, we bring together a multi-disciplinary team to propose the Effect and Mechanism of Acupuncture for Cancer-related Cognitive Impairment (ENHANCE) trial. We found that nearly 80% of breast cancer survivors with CRCI report insomnia, echoing the growing research on connections between cognition and sleep. Thus, we will recruit 260 breast cancer survivors with CRCI and insomnia and randomize them to one of 3 conditions in an RCT: 1) acupuncture, 2) sham acupuncture (SA), or 3) usual-care wait-list control (WLC). We will collect serum BDNF and patient-reported/objective measures of cognition and sleep from baseline to Week 26. The Specific Aims are 1) to determine the effects of acupuncture on perceived CRCI and objective cognitive function; 2) to evaluate the mechanism of acupuncture on perceived CRCI and objective cognitive function via BDNF; and 3) to elucidate the role of insomnia on perceived CRCI and objective cognitive function in context of acupuncture. If successful, our study would expand treatment options for CRCI, advance mechanistic understanding of acupuncture, and disentangle the relationship between sleep and cognition, helping to shift the treatment paradigm towards a personalized model that targets CRCI phenotypes based on BDNF profile and insomnia.