Department of Diagnostic Radiology, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, 91010, USA.
Center for Cancer and Aging, City of Hope National Medical Center, Duarte, CA, 91010, USA.
Brain Imaging Behav. 2022 Feb;16(1):43-53. doi: 10.1007/s11682-021-00475-y. Epub 2021 May 21.
Chemotherapy may impair cognition and contribute to accelerated aging. The purpose of this study was to assess the effects of chemotherapy on the connectivity of the default mode network (DMN) in older women with breast cancer. This prospective longitudinal study enrolled women aged ≥ 60 years with stage I-III breast cancer (CTx group) and matched healthy controls (HC group). Study assessments, consisting of resting-state functional MRI (rs-fMRI) and the Picture Sequence Memory (psm) test for episodic memory from the NIH Toolbox for Cognition, were obtained at baseline and within one month after the completion of chemotherapy for the CTx group and at matched intervals for the HC group. Two-sample t-test and FDR multiple comparison were used for statistical inference. Our analysis of the CTx group (N = 19; 60-82 years of age, mean = 66.6, SD = 5.24) compared to the HC group (N = 14; 60-78 years of age, mean = 68.1, SD = 5.69) revealed weaker DMN subnetwork connectivity in the anterior brain but stronger connectivity in the posterior brain at baseline. After chemotherapy, this pattern was reversed, with stronger anterior connectivity and weaker posterior connectivity. In addition, the meta-level functional network connectivity (FNC) among the DMN subnetworks after chemotherapy was consistently weaker than the baseline FNC as seen in the couplings between anterior cingulate cortex (ACC) and retrosplenial (rSplenia) region, with ΔFNC('ACC','rSplenia')=-0.14, t value=-2.44, 95 %CI=[-0.27,-0.10], p<0.05). The baseline FNC matrices of DMN subnetworks were correlated with psm scores (corr = 0.58, p < 0.05). Our results support DMN alterations as a potential neuroimaging biomarker for cancer-related cognitive impairment and accelerated aging.
化疗可能会损害认知能力，并导致加速衰老。本研究的目的是评估化疗对老年乳腺癌女性默认模式网络（DMN）连接的影响。这项前瞻性纵向研究纳入了年龄≥60 岁的 I-III 期乳腺癌女性（CTx 组）和匹配的健康对照组（HC 组）。研究评估包括静息态功能磁共振成像（rs-fMRI）和 NIH 认知工具箱中的图片序列记忆（psm）测试，用于评估情景记忆，分别在 CTx 组化疗结束后一个月内和 HC 组的匹配时间点进行。使用双样本 t 检验和 FDR 多重比较进行统计推断。我们对 CTx 组（N=19；60-82 岁，平均年龄=66.6，标准差=5.24）与 HC 组（N=14；60-78 岁，平均年龄=68.1，标准差=5.69）的分析显示，在基线时，前脑的 DMN 子网连接较弱，但后脑的连接较强。化疗后，这种模式发生了逆转，前脑连接增强，后脑连接减弱。此外，化疗后 DMN 子网之间的元级功能网络连接（FNC）始终弱于基线 FNC，如前扣带皮层（ACC）和后扣带回（rSplenia）之间的耦合，ΔFNC（'ACC'，'rSplenia'）=-0.14，t 值=-2.44，95%CI=[-0.27，-0.10]，p<0.05）。DMN 子网的基线 FNC 矩阵与 psm 评分相关（corr=0.58，p<0.05）。我们的结果支持 DMN 改变作为癌症相关认知障碍和加速衰老的潜在神经影像学生物标志物。
