Neurofilament light (NFL) is an emerging marker of axonal degeneration. This study investigated the relationship between white matter hyperintensities (WMHs) and plasma NFL in a large elderly cohort with, and without, cognitive impairment. We used the Alzheimer's Disease Neuroimaging Initiative and included 163 controls, 103 participants with a significant memory concern, 279 with early mild cognitive impairment (EMCI), 152 with late mild cognitive impairment (LMCI), and 130 with Alzheimer's disease, with 3T MRI and plasma NFL data. Multiple linear regression models examined the relationship between WMHs and NFL, with and without age adjustment. We used smoking status, history of hypertension, history of diabetes, and BMI as additional covariates to examine the effect of vascular risk. We found increases of between 20% and 41% in WMH volume per 1SD increase in NFL in significant memory concern, early mild cognitive impairment, late mild cognitive impairment, and Alzheimer's disease groups (p < 0.02). Marked attenuation of the positive associations between WMHs and NFL were seen after age adjustment, suggesting that a significant proportion of the association between NFL and WMHs is age-related. No effect of vascular risk was observed. These results are supportive of a link between WMH and axonal degeneration in early to late disease stages, in an age-dependent, but vascular risk-independent manner.

中文翻译：

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早期和晚期阿尔茨海默病中白质高信号和神经丝光的年龄依赖性关联

神经丝光 (NFL) 是轴索变性的新兴标志物。本研究调查了一个大型老年人群中白质高信号 (WMH) 和血浆 NFL 之间的关系，有或没有认知障碍。我们使用了阿尔茨海默病神经影像学计划，包括 163 名对照者、103 名有显着记忆问题的参与者、279 名早期轻度认知障碍 (EMCI)、152 名晚期轻度认知障碍 (LMCI) 和 130 名阿尔茨海默病患者，通过 3T MRI 和血浆 NFL 数据。多元线性回归模型检查了 WMH 和 NFL 之间的关系，无论有无年龄调整。我们使用吸烟状况、高血压病史、糖尿病病史和 BMI 作为额外协变量来检查血管风险的影响。我们发现，在显着记忆问题、早期轻度认知障碍、晚期轻度认知障碍和阿尔茨海默病组中，NFL 每增加 1SD，WMH 体积增加 20% 至 41%（p < 0.02）。在调整年龄后，WMH 和 NFL 之间的正相关性显着减弱，这表明 NFL 和 WMH 之间的相关性有很大一部分与年龄相关。没有观察到血管风险的影响。这些结果支持 WMH 与疾病早期到晚期的轴突变性之间的联系，这种联系与年龄相关，但与血管风险无关。在调整年龄后，WMH 和 NFL 之间的正相关性明显减弱，这表明 NFL 和 WMH 之间的相关性有很大一部分与年龄相关。没有观察到血管风险的影响。这些结果支持 WMH 与疾病早期到晚期的轴突变性之间的联系，这种联系与年龄相关，但与血管风险无关。在调整年龄后，WMH 和 NFL 之间的正相关性显着减弱，这表明 NFL 和 WMH 之间的相关性有很大一部分与年龄相关。没有观察到血管风险的影响。这些结果支持 WMH 与疾病早期到晚期的轴突变性之间的联系，这种联系与年龄相关，但与血管风险无关。