Center for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 355 W. 16th St., GH Suite 4100, Indianapolis, IN, 46202, USA.
Brain Imaging Behav. 2013 Dec;7(4):491-500. doi: 10.1007/s11682-013-9240-5.
Chemotherapy-induced amenorrhea (CIA) often occurs in pre- and peri-menopausal BC patients, and while cancer/chemotherapy and abrupt estrogen loss have separately been shown to affect cognition and brain function, studies of the cognitive effects of CIA are equivocal, and its effects on brain function are unknown. Functional MRI (fMRI) during a working memory task was used to prospectively assess the pattern of brain activation and deactivation prior to and 1 month after chemotherapy in BC patients who experienced CIA (n = 9), post-menopausal BC patients undergoing chemotherapy (n = 9), and pre- and post-menopausal healthy controls (n = 6 each). Neurocognitive testing was also performed at both time points. Repeated measures general linear models were used to assess statistical significance, and age was a covariate in all analyses. We observed a group-by-time interaction in the combined magnitudes of brain activation and deactivation (p = 0.006): the CIA group increased in magnitude from baseline to post-treatment while other groups maintained similar levels over time. Further, the change in brain activity magnitude in CIA was strongly correlated with change in processing speed neurocognitive testing score (r = 0.837 p = 0.005), suggesting this increase in brain activity reflects effective cognitive compensation. Our results demonstrate prospectively that the pattern of change in brain activity from pre- to post-chemotherapy varies according to pre-treatment menopausal status. Cognitive correlates add to the potential clinical significance of these findings. These findings have implications for risk appraisal and development of prevention or treatment strategies for cognitive changes in CIA.
化疗引起的闭经（CIA）常发生于绝经前和围绝经期乳腺癌患者中，虽然癌症/化疗和雌激素突然缺失分别被证明会影响认知和大脑功能，但 CIA 对认知影响的研究结果并不一致，其对大脑功能的影响也尚不清楚。我们前瞻性地使用功能磁共振成像（fMRI）在化疗前和化疗后 1 个月评估经历 CIA（n=9）、接受化疗的绝经后乳腺癌患者（n=9）和绝经前及绝经后健康对照者（每组 n=6）的大脑激活和失活模式，在两个时间点也进行了神经认知测试。采用重复测量一般线性模型评估统计学意义，所有分析均将年龄作为协变量。我们观察到联合大脑激活和失活幅度的组间-时间交互作用（p=0.006）：CIA 组从基线到治疗后增加，而其他组随时间保持相似水平。此外，CIA 中大脑活动幅度的变化与处理速度神经认知测试评分的变化强烈相关（r=0.837，p=0.005），表明大脑活动的这种增加反映了有效的认知补偿。我们的结果前瞻性地表明，从化疗前到化疗后的大脑活动变化模式根据治疗前的绝经状态而不同。认知相关性增加了这些发现的潜在临床意义。这些发现对 CIA 中认知变化的风险评估和预防或治疗策略的制定具有重要意义。
