OBJECTIVE Elevated inflammation is associated with worse late-life cognitive functioning and brain health. Our goal was to examine the relationship between inflammation trajectories and white matter integrity in midlife. METHODS Participants were 508 adults from the Coronary Artery Risk Development in Young Adults Study (CARDIA; 51% female). Latent class analysis was used to identify inflammation trajectories based on repeated measures of the inflammatory marker C-reactive protein (CRP) over the 18 years before brain magnetic resonance imaging (MRI). Outcomes were brain MRI measures of total and region-specific white matter volume and integrity at a mean age of 50.6±3.4 years. Linear regression was used to examine if inflammation trajectories were associated with brain MRI outcomes, adjusting for potential confounds in all models and for disease and health behaviors in follow-up models. RESULTS Lower-stable (38%), moderate-increasing (7%), and consistently-higher (54%), trajectories emerged. Compared to the lower-stable group, the moderate-increasing group showed lower white matter volume (β = -0.18, 95% CI -0.29, -0.06) and worse white matter integrity as indexed by lower fractional anisotropy (FA; β = -0.37, 95% CI -0.70, -0.04) and higher mean diffusivity (β = 0.44, 95% CI 0.11, 0.78) in the whole brain. The consistently-higher group showed lower whole-brain FA (β = -0.20, -0.38, -0.03). In exploratory analyses, the moderate-increasing group showed lower white matter volume, lower FA and higher MD in the frontal, temporal, and parietal lobes compared to the lower-stable group. The consistently-higher group showed lower white matter volume in the parietal lobe and lower FA in the frontal, temporal, and parietal lobes, but similar MD, compared to the lower-stable group. Findings for the moderate-increasing, but not the consistently-higher, group were robust to adjustment for disease and lifestyle factors. CONCLUSION Increasing or high inflammation trajectories from early to mid adulthood are associated with worse brain health, as indexed by lower white matter volume and/or worse white matter integrity.

中文翻译：

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中年炎症轨迹与白质体积和完整性的关系

目的 炎症升高与晚年认知功能和大脑健康状况恶化有关。我们的目标是检查中年炎症轨迹与白质完整性之间的关系。方法 参与者是来自年轻成人冠状动脉风险发展研究（CARDIA；51% 女性）的 508 名成年人。在脑磁共振成像 (MRI) 之前的 18 年中，基于炎症标志物 C 反应蛋白 (CRP) 的重复测量，使用潜在类别分析来识别炎症轨迹。结果是平均年龄为 50.6±3.4 岁的大脑 MRI 测量总和特定区域的白质体积和完整性。线性回归用于检查炎症轨迹是否与脑 MRI 结果相关，调整所有模型中的潜在混淆以及后续模型中的疾病和健康行为。结果 出现了较低稳定 (38%)、中等增加 (7%) 和持续较高 (54%) 的轨迹。与稳定性较低的组相比，中等增加的组显示出较低的白质体积 (β = -0.18, 95% CI -0.29, -0.06) 和较低的各向异性分数 (FA; β = - 0.37, 95% CI -0.70, -0.04) 和更高的平均扩散率 (β = 0.44, 95% CI 0.11, 0.78) 在整个大脑中。始终较高的组显示较低的全脑 FA (β = -0.20, -0.38, -0.03)。在探索性分析中，与稳定性较低的组相比，适度增加组的额叶、颞叶和顶叶的白质体积较低，FA 较低，MD 较高。与稳定性较低的组相比，持续较高的组显示出较低的顶叶白质体积和较低的额叶、颞叶和顶叶的 FA，但 MD 相似。适度增加但不是持续增加的组的结果对疾病和生活方式因素的调整是稳健的。结论 从成年早期到中期，炎症轨迹增加或升高与大脑健康状况恶化有关，这表现为白质体积降低和/或白质完整性变差。