Webster Rachel T, Mirzaei Sedigheh, Bhatia Shalini, Srivastava Deo Kumar, Mostoufi-Moab Sogol, Dixon Stephanie B, Chow Eric J, Armstrong Gregory T, Krull Kevin R, van der Plas Ellen
St Jude Children's Research Hospital, Memphis, Tennessee, USA.
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Cancer. 2025 Aug 15;131(16):e70011. doi: 10.1002/cncr.70011.
The objective of this research was to examine associations between diabetes mellitus (DM) and neurocognitive impairment in survivors of childhood cancer while exploring mechanistic associations with treatment exposures and moderating associations with cardiovascular disease (CVD) and risky lifestyle factors.
Survivors of the Childhood Cancer Survivor Study (N = 16,196; mean ± standard deviation age, 32.9 ± 7.9 years; 50.2% female; N = 615 with DM) self-reported neurocognitive functioning, risky drinking, physical inactivity, and tobacco use. Medical data were collected from chart review. Multivariable regression determined the association of DM with neurocognitive impairment while adjusting for relevant treatment exposures. Interactions between DM and treatment, risky lifestyle, and cardiovascular predictors on impairment were explored. Path analysis was used to examine the effects of treatment exposures through DM and CVD on impairment. Among survivors with DM, multivariable regressions examined predictors of neurocognitive change over time (mean, 11.21 years).
Survivors with DM had an increased risk of impairment relative to survivors without DM (task completion: odds ratio [OR], 1.5; 95% confidence limits [CI], 1.2-1.9; emotion regulation: OR, 1.4; 95% CI, 1.1-2.0; and organization: OR, 1.5; 95% CI, 1.1-2.0). The effects of cranial radiation on neurocognition were mediated by DM, including task completion (β = 0.02), emotion regulation (β = 0.02), memory (β = 0.01), and organization (β = 0.02; all p < .01). Among survivors with DM, CVD was associated with declines in task completion (estimate = 0.44; p < .01) and organization (estimate = 0.27; p = .03).
Survivors with DM are at increased risk of neurocognitive impairment. Although CVD did not exacerbate concurrent risk for impairment, it was associated with a decline in neurocognitive functioning over time in survivors with DM. Preventing/managing CVD in survivors with DM could mitigate additional neurocognitive decline.
本研究的目的是探讨儿童癌症幸存者中糖尿病（DM）与神经认知障碍之间的关联，同时探索与治疗暴露的机制关联以及与心血管疾病（CVD）和危险生活方式因素的调节关联。
儿童癌症幸存者研究的幸存者（N = 16,196；平均±标准差年龄，32.9±7.9岁；50.2%为女性；N = 615患有DM）自我报告神经认知功能、危险饮酒、身体活动不足和吸烟情况。通过病历审查收集医疗数据。多变量回归确定了DM与神经认知障碍之间的关联，同时对相关治疗暴露进行了调整。探讨了DM与治疗、危险生活方式和心血管预测因素对障碍的相互作用。路径分析用于研究治疗暴露通过DM和CVD对障碍的影响。在患有DM的幸存者中，多变量回归研究了神经认知随时间变化（平均11.21年）的预测因素。
与无DM的幸存者相比，患有DM的幸存者出现障碍的风险增加（任务完成：优势比[OR]，1.5；95%置信区间[CI]，1.2 - 1.9；情绪调节：OR，1.4；95% CI，1.1 - 2.0；组织能力：OR，1.5；95% CI，1.1 - 2.0）。颅脑放疗对神经认知的影响由DM介导，包括任务完成（β = 0.02）、情绪调节（β = 0.02）、记忆（β = 0.01）和组织能力（β = 0.02；均p <.01）。在患有DM的幸存者中，CVD与任务完成能力下降（估计值 = 0.44；p <.01）和组织能力下降（估计值 = 0.27；p =.03）相关。
患有DM的幸存者神经认知障碍风险增加。虽然CVD并未加剧同时存在的障碍风险，但它与患有DM的幸存者随时间神经认知功能下降相关。预防/管理患有DM的幸存者中的CVD可减轻额外的神经认知衰退。
