Li Danni, Zhang Lin, Nelson Nathaniel W, Mielke Michelle M, Yu Fang
Department of Lab Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
School of Public Health, Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA.
J Alzheimers Dis Rep. 2021 Jul 21;5(1):601-611. doi: 10.3233/ADR-210302. eCollection 2021.
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, = 0.02853) and in ADL from baseline to 12 months (standardized estimate of -0.00284, = 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], = 0.01635; standardized estimate of -0.03818, = 0.0435) and greater rate of decline in ADL from 3 to 12 month (standardized estimate of -0.01492, = 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.
血液生物标志物在阿尔茨海默病（AD）临床试验中的作用尚不清楚。
评估血浆神经丝轻链（NfL）预测FIT-AD试验中26名轻度至中度AD痴呆老年人未来认知和日常生活活动（ADL）结果下降的能力。
在基线、3个月和6个月时测量血浆NfL。分别在基线、3、6、9和12个月时，使用AD认知评估量表（ADAS-Cog）、AD统一数据集工具和痴呆残疾评估量表（DAD）评估认知和ADL。采用线性混合效应模型检查基线或血浆NfL变化与结果变化之间的关联。
较高的基线血浆NfL与从基线到6个月ADAS-Cog的更大下降率（标准化估计值为0.00462，P = 0.02853）以及从基线到12个月ADL的更大下降率（标准化估计值为-0.00284，P = 0.03338）相关。从基线到3个月短期血浆NfL的更大增加与从3到6个月记忆和ADL的更大下降率（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）以及从3到12个月ADL的更大下降率（标准化估计值为-0.01492，P = 0.01082）相关。
本研究表明，血浆NfL可能有预测长达12个月认知和功能下降的潜力。然而，未来需要更大样本量的研究来证实这些发现。
