About one-in-three breast cancer survivors have lingering cognitive complaints and objective cognitive impairment. Chronic inflammation and intestinal permeability (i.e., leaky gut), two risk factors for cognitive decline, can also fuel depression—another vulnerability for cognitive decline. The current study tested whether depression accompanied by high levels of inflammation or intestinal permeability predicted lower subjective and objective cognitive function in breast cancer survivors. We combined data from four breast cancer survivor studies (n= 613); some had repeated measurements for a total of 1015 study visits. All participants had a blood draw to obtain baseline measures of lipopolysaccharide binding protein—a measure of intestinal permeability, as well as three inflammatory markers that were incorporated into an inflammatory index: C-reactive protein, interleukin-6, and tumor necrosis factor-α. They reported depressive symptoms on the Center for Epidemiological Studies depression scale (CES-D), and a binary variable indicated clinically significant depressive symptoms (CES-D ≥ 16). The Kohli (749 observations) and the Breast Cancer Prevention Trial (591 observations) scales assessed subjective cognitive function. Objective cognitive function tests included the trail-making test, Hopkins verbal learning test, Conners continuous performance test, n-back test, FAS test, and animal-naming test (239–246 observations). Adjusting for education, age, BMI, cancer treatment type, time since treatment, study visit, and fatigue, women who had clinically elevated depressive symptoms accompanied by heightened inflammation or intestinal permeability reported poorer focus and marginally poorer memory. However, poorer performance across objective cognitive measures was not specific to inflammation-associated depression. Rather, there was some evidence of lower verbal fluency; poorer attention, verbal learning and memory, and working memory; and difficulties with visuospatial search among depressed survivors, regardless of inflammation. By themselves, inflammation and intestinal permeability less consistently predicted subjective or objective cognitive function. Breast cancer survivors with clinically significant depressive symptoms accompanied by either elevated inflammation or intestinal permeability may perceive greater cognitive difficulty, even though depression-related objective cognitive deficits may not be specific to inflammation- or leaky-gut-associated depression.
约三分之一的乳腺癌幸存者存在持续的认知抱怨及客观认知功能损害。慢性炎症与肠道通透性增加（即肠漏）作为认知衰退的两大风险因素，亦可加剧抑郁症状——后者同样是认知功能下降的易感因素。本研究旨在验证在乳腺癌幸存者中，伴随高水平炎症或肠道通透性增加的抑郁症状是否能预测更差的主客观认知功能。我们整合了四项乳腺癌幸存者研究数据（n=613），其中部分参与者接受重复测量，累计完成1015次研究访视。所有参与者均接受血液检测，获取基线水平的脂多糖结合蛋白（肠道通透性指标）以及三种炎症标志物（C反应蛋白、白细胞介素-6、肿瘤坏死因子-α），后三者被整合为炎症指数。采用流行病学研究中心抑郁量表评估抑郁症状，并以二分变量界定具有临床意义的抑郁症状（CES-D≥16分）。主观认知功能通过Kohli量表（749次观测）和乳腺癌预防试验量表（591次观测）评估。客观认知功能测试包括连线测试、霍普金斯词语学习测试、康纳斯持续操作测试、n-back测试、FAS词语流畅性测试及动物命名测试（239-246次观测）。在调整教育程度、年龄、体重指数、癌症治疗类型、治疗后时间、研究访视及疲劳程度后，研究发现：伴有炎症水平升高或肠道通透性增加的临床显著抑郁症状女性，其自我报告专注力显著下降，记忆力亦呈现边际性减退。然而，客观认知测试表现较差并非炎症相关抑郁所特有。相反，有证据表明抑郁幸存者存在言语流畅性下降，注意力、词语学习记忆和工作记忆功能减退，以及视觉空间搜索困难，且这些表现与炎症水平无关。单独分析时，炎症与肠道通透性指标对主客观认知功能的预测作用较不稳定。研究提示，伴有炎症水平升高或肠道通透性增加的临床显著抑郁症状的乳腺癌幸存者可能感知到更严重的认知困难，尽管抑郁相关的客观认知缺陷未必特发于炎症或肠漏相关的抑郁亚型。
肿瘤(癌症)患者之家