Charles F. and Joanne Knight Alzheimer's Disease Research Center, Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
J Alzheimers Dis. 2020;74(4):1119-1129. doi: 10.3233/JAD-200018.
Cerebrospinal fluid tau and neurofilament light (NfL) are two biomarkers of neurodegeneration in Alzheimer's disease. Previous reports have shown that the influence of tau on cognitive decline depends on levels of amyloid burden whereas NfL predicts decline independently of amyloid. Most studies use a global cognitive composite as the primary outcome, and it is unknown if critical cognitive domain scores are similarly sensitive to rates of decline due to neurodegeneration.
To examine the unique contribution of amyloid, tau, and NfL to rates of cognitive decline in multiple cognitive composites in a cognitively healthy, middle-aged to older adult cohort.
A total of 255 participants (55% female; mean age = 66.2 years, range = 42.5-86.7 years) completed CSF studies and serial cognitive assessments to measure global cognition, episodic memory, and attentional control. Linear mixed effects models were used to examine rates of change on each composite score as a function of baseline biomarker levels.
Total tau predicted decline in attention regardless of amyloid status, but the relationship to global cognition and episodic memory was dependent on amyloid, replicating prior literature. NfL predicted decline in attention and global cognition, but not memory, and this effect was independent of amyloid status.
These findings suggest that NfL can be used to monitor cognitive decline in aging and Alzheimer's disease and that an attentional control composite may be a better outcome for tracking general neurodegenerative effects on cognition.
脑脊液中的 tau 和神经丝轻链（NfL）是阿尔茨海默病神经退行性变的两种生物标志物。先前的报告表明，tau 对认知下降的影响取决于淀粉样蛋白负担的水平，而 NfL 则独立于淀粉样蛋白预测下降。大多数研究使用整体认知综合得分作为主要结果，而不清楚关键认知域评分是否同样对神经退行性变导致的下降速度敏感。
在认知健康的中年至老年人群队列中，检查淀粉样蛋白、tau 和 NfL 对多种认知综合得分下降速度的独特贡献。
共有 255 名参与者（55%为女性；平均年龄为 66.2 岁，范围为 42.5-86.7 岁）完成了 CSF 研究和连续认知评估，以测量整体认知、情景记忆和注意力控制。线性混合效应模型用于检查每个综合得分的变化率作为基线生物标志物水平的函数。
tau 总量无论淀粉样蛋白状态如何，都可以预测注意力下降，但与整体认知和情景记忆的关系取决于淀粉样蛋白，这与先前的文献一致。NfL 预测注意力和整体认知下降，但不预测记忆下降，且这种影响独立于淀粉样蛋白状态。
这些发现表明，NfL 可用于监测衰老和阿尔茨海默病中的认知下降，且注意力控制综合得分可能是跟踪认知中一般神经退行性变化的更好结果。
