我们评估了老年乳腺癌幸存者中血浆阿尔茨海默病 (AD) 相关生物标志物是否与癌症相关认知能力下降 (CRCD) 相关。我们纳入了患有原发性 0-III 期乳腺癌的 60-90 岁幸存者 (n = 236) 和频率匹配的非癌症对照（n = 154）通过了认知筛查并储存了血浆样本。参与者在基线（系统治疗前）和每年一次进行评估，持续长达 60 个月。通过注意力、处理速度和执行功能（APE）以及学习和记忆（LM）测试来测量认知能力；感知认知通过 FACT-Cog PCI 进行测量。使用单分子阵列测定基线血浆神经丝光 (NfL)、神经胶质原纤维酸性蛋白 (GFAP)、β-淀粉样蛋白 42/40 (Aβ42/40) 和磷酸化 tau (p-tau181)。混合模型测试了认知和基线 AD 生物标志物、时间、群体（幸存者与对照组）之间的关联及其双向和三向交互作用，控制了年龄、种族、WRAT4 单词阅读分数、合并症和 BMI；两侧 0.05 p 值被认为具有统计显着性。除了幸存者的基线 NfL 水平高于对照组之外，基线 AD 相关生物标志物没有组间差异 (p = .013)。从基线开始并随着时间的推移，幸存者的调整后纵向 APE 低于对照组（p = <0.002）。然而，基线 AD 相关生物标志物水平与随着时间的推移调整的认知并不独立相关，除了对照组的 APE 评分较低而 GFAP 水平较高 (p = .008)。结果不支持基线 AD 相关生物标志物与 CRCD 之间的关系。需要进一步的调查来证实这些发现，测试 AD 相关生物标志物纵向变化的影响，并检查影响认知前系统治疗的其他机制和因素。© 作者 2024。由牛津大学出版社出版。版权所有。如需权限，请发送电子邮件至：journals.permissions@oup.com。

We evaluated whether plasma Alzheimer's Disease (AD)-related biomarkers were associated with cancer-related cognitive decline (CRCD) among older breast cancer survivors.We included survivors 60-90 years with primary stage 0-III breast cancers (n = 236) and frequency-matched non-cancer controls (n = 154) who passed a cognitive screen and had banked plasma specimens. Participants were assessed at baseline (pre-systemic therapy) and annually for up to 60-months. Cognition was measured using tests of attention, processing speed and executive function (APE) and learning and memory (LM); perceived cognition was measured by the FACT-Cog PCI. Baseline plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), beta-amyloid 42/40 (Aβ42/40) and phosphorylated tau (p-tau181) were assayed using single molecule arrays. Mixed models tested associations between cognition and baseline AD-biomarkers, time, group (survivor vs control) and their two- and three-way interactions, controlling for age, race, WRAT4 Word Reading score, comorbidity and BMI; two-sided 0.05 p-values were considered statistically significant.There were no group differences in baseline AD-related biomarkers except survivors had higher baseline NfL levels than controls (p = .013). Survivors had lower adjusted longitudinal APE than controls starting from baseline and continuing over time (p = <0.002). However, baseline AD-related biomarker levels were not independently associated with adjusted cognition over time, except controls had lower APE scores with higher GFAP levels (p = .008).The results do not support a relationship between baseline AD-related biomarkers and CRCD. Further investigation is warranted to confirm the findings, test effects of longitudinal changes in AD-related biomarkers and examine other mechanisms and factors affecting cognition pre-systemic therapy.© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.