Plasma Neurofilament Light and Future Declines in Cognition and Function in Alzheimer's Disease in the FIT-AD Trial.
Plasma Neurofilament Light and Future Declines in Cognition and Function in Alzheimer's Disease in the FIT-AD Trial.
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DOI：
10.3233/adr-210302
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Yu F
中科院分区：
文献类型：
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作者：
Li D;Zhang L;Nelson NW;Mielke MM;Yu F
基于血液的生物标志物在阿尔茨海默病（AD）临床试验中的效用仍然未知。评价血浆神经丝轻链（NfL）预测来自FIT-AD试验的26例轻度至中度AD痴呆老年人未来认知和日常生活活动（ADL）结局下降的能力。在基线、3个月和6个月时测量血浆NfL。在基线、3、6、9和12个月时，分别使用AD评估量表-认知（ADAS-Cog）和AD统一数据集工具和痴呆残疾评估（DAD）评估认知和ADL。线性混合效应模型用于检查基线或血浆NfL变化与结局变化之间的相关性。基线血浆NfL较高与ADAS-Cog自基线至6个月（标准化估计值为0.00462，p = 0.02853）和ADL自基线至12个月（标准化估计值为-0.00284，p = 0.03338）的下降率较大相关。 从基线至3个月的短期内血浆NfL增加较大，与3至6个月的记忆力和ADL下降率较大（标准化估计值为-0.04638 [0.003]，p = 0.01635;标准化估计值为-0.03818，p = 0.0435）以及3至12个月的ADL下降率较大（标准化估计值为-0.01492，p = 0.01082）相关。 这项研究表明，血浆NfL可能具有预测长达12个月的认知和功能下降的潜力。然而，未来更大样本量的研究需要证实这些发现。
Utilities of blood-based biomarkers in Alzheimer’s disease (AD) clinical trials remain unknown. To evaluate the ability of plasma neurofilament light chain (NfL) to predict future declines in cognition and activities of daily living (ADL) outcomes in 26 older adults with mild-to-moderate AD dementia from the FIT-AD Trial. Plasma NfL was measured at baseline and 3 and 6 months. Cognition and ADL were assessed using the AD Assessment Scale-Cognition (ADAS-Cog) and AD Uniform Dataset Instruments and Disability Assessment for Dementia (DAD), respectively, at baseline, 3, 6, 9, and 12 months. Linear mixed effects models were used to examine the associations between baseline or change in plasma NfL and changes in outcomes. Higher baseline plasma NfL was associated with greater rate of decline in ADAS-Cog from baseline to 6 months (standardized estimate of 0.00462, p = 0.02853) and in ADL from baseline to 12 months (standardized estimate of –0.00284, p = 0.03338). Greater increase in plasma NfL in short term from baseline to 3 months was associated with greater rate of decline in memory and ADL from 3 to 6 months (standardized estimate of –0.04638 [0.003], p = 0.01635; standardized estimate of –0.03818, p = 0.0435) and greater rate of decline in ADL from 3 to 12 month (standardized estimate of –0.01492, p = 0.01082). This study demonstrated that plasma NfL might have the potential to predict cognitive and function decline up to 12 months. However, future studies with bigger sample sizes need to confirm the findings.