Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, Los Angeles, CA.
Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry & Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA.
J Clin Oncol. 2023 Jan 10;41(2):295-306. doi: 10.1200/JCO.22.00406. Epub 2022 Sep 30.
To examine longitudinal relationships between levels of C-reactive protein (CRP) and cognition in older breast cancer survivors and noncancer controls.
English-speaking women age ≥ 60 years, newly diagnosed with primary breast cancer (stage 0-III), and frequency-matched controls were enrolled from September 2010 to March 2020; women with dementia, neurologic disorders, and other cancers were excluded. Assessments occurred presystemic therapy/enrollment and at annual visits up to 60 months. Cognition was measured using the Functional Assessment of Cancer Therapy-Cognitive Function and neuropsychological testing. Mixed linear effect models tested for survivor-control differences in natural log (ln)-transformed CRP at each visit. Random effect-lagged fluctuation models tested directional effects of ln-CRP on subsequent cognition. All models controlled for age, race, study site, cognitive reserve, obesity, and comorbidities; secondary analyses evaluated if depression or anxiety affected results.
There were 400 survivors and 329 controls with CRP specimens and follow-up data (average age of 67.7 years; range, 60-90 years). The majority of survivors had stage I (60.9%), estrogen receptor-positive (87.6%) tumors. Survivors had significantly higher adjusted mean ln-CRP than controls at baseline and 12-, 24-, and 60-month visits (all < .05). Higher adjusted ln-CRP predicted lower participant-reported cognition on subsequent visits among survivors, but not controls ( interaction = .008); effects were unchanged by depression or anxiety. Overall, survivors had adjusted Functional Assessment of Cancer Therapy-Cognitive Function scores that were 9.5 and 14.2 points lower than controls at CRP levels of 3.0 and 10.0 mg/L. Survivors had poorer neuropsychological test performance ( controls), with significant interactions with CRP only for the Trails B test.
Longitudinal relationships between CRP and cognition in older breast cancer survivors suggest that chronic inflammation may play a role in development of cognitive problems. CRP testing could be clinically useful in survivorship care.
研究老年乳腺癌幸存者和非癌症对照者体内 C 反应蛋白（CRP）水平与认知功能之间的纵向关系。
本研究纳入了 2010 年 9 月至 2020 年 3 月期间新诊断为原发性乳腺癌（0-III 期）且英语交流无障碍的年龄≥60 岁的女性患者和频率匹配的对照组患者；排除痴呆、神经疾病和其他癌症患者。在系统治疗/入组前和每年随访（最多 60 个月）时进行评估。采用癌症治疗功能评估-认知功能和神经心理学测试来测量认知功能。混合线性效应模型检验了每个就诊时幸存者和对照组患者体内 CRP 的自然对数（ln）变换值之间的差异。随机效应滞后波动模型检验了 CRP 对随后认知功能的定向影响。所有模型均控制了年龄、种族、研究地点、认知储备、肥胖和合并症；次要分析评估了抑郁或焦虑是否影响结果。
有 400 名幸存者和 329 名对照者具有 CRP 标本和随访数据（平均年龄 67.7 岁；范围，60-90 岁）。大多数幸存者的肿瘤分期为 I 期（60.9%），雌激素受体阳性（87.6%）。与对照组相比，幸存者在基线及就诊后 12、24 和 60 个月时的 CRP 水平均显著升高（均<0.05）。在幸存者中，CRP 水平升高与随后就诊时的认知功能下降显著相关，但在对照组中无此相关性（交互作用=0.008）；抑郁或焦虑并未改变这一结果。总的来说，CRP 水平为 3.0 和 10.0 mg/L 时，幸存者的癌症治疗功能评估-认知功能评分比对照组分别低 9.5 和 14.2 分。幸存者的神经心理学测试表现较差（对照组），只有在追踪 B 测试中 CRP 才与认知功能存在显著交互作用。
老年乳腺癌幸存者体内 CRP 与认知功能之间的纵向关系表明，慢性炎症可能在认知问题的发生发展中起作用。CRP 检测在癌症幸存者护理中可能具有临床应用价值。
