ANU Medical School, Australian National University, Canberra, Australia.
Centre for Research on Ageing, Health and Wellbeing, Australian National University, Canberra, Australia.
J Alzheimers Dis. 2021;82(3):951-964. doi: 10.3233/JAD-210092.
Individuals with mild cognitive impairment (MCI) are at high risk of progression to Alzheimer's disease (AD) dementia, but some remain stable. There is a need to identify those at higher risk of progression to improve patient management and outcomes.
To evaluate the trajectory of plasma neurofilament light chain (pNFL) prior to progression from MCI to AD dementia, the performance of pNFL, in combination with the Mini-Mental State Examination (MMSE), as a predictor of progression from MCI to AD dementia and to inform clinicians on the use of pNFL as a predictive biomarker.
Participants (n = 440) with MCI and longitudinal follow-up (mean = 4.2 years) from the AD Neuroimaging Initiative dataset were included. pNFL as a marker for neurodegeneration and the MMSE as a cognitive measure were investigated as simple/practical predictors of progression. The risk of progressing from MCI to AD dementia associated with pNFL and MMSE scores was assessed using Cox and logistic regression models.
The current risk of progression to AD dementia was 37%higher in individuals with high pNFL (> 56 ng/L) compared to those with average pNFL (≤40 ng/L). A combination of baseline pNFL and MMSE could differentiate those who progressed within 5 years (AUC = 0.75) from stable individuals. Including change in MMSE over 6-12 months further improved the model (AUC = 0.84).
Our findings reveal that combining pNFL with a simple dementia screener (MMSE) can reliably predict whether a person with MCI is likely to progress to AD dementia within 5 years.
轻度认知障碍（MCI）个体发生阿尔茨海默病（AD）痴呆的风险较高，但也有一些个体保持稳定。因此，需要确定那些进展风险较高的患者，以改善患者的管理和结局。
评估 MCI 进展为 AD 痴呆前血浆神经丝轻链（pNFL）的轨迹，以及 pNFL 与简易精神状态检查（MMSE）相结合作为预测 MCI 进展为 AD 痴呆的指标的性能，并为临床医生提供使用 pNFL 作为预测生物标志物的信息。
纳入来自 AD 神经影像学倡议数据集的 440 名 MCI 患者和纵向随访（平均 4.2 年）。将 pNFL 作为神经退行性变的标志物和 MMSE 作为认知测量，作为进展的简单/实用预测指标进行研究。使用 Cox 和逻辑回归模型评估 pNFL 和 MMSE 评分与从 MCI 进展为 AD 痴呆相关的风险。
与 pNFL 和 MMSE 评分平均值（≤40ng/L）相比，pNFL 较高（>56ng/L）的个体进展为 AD 痴呆的当前风险高 37%。基线 pNFL 和 MMSE 的组合可以区分出在 5 年内进展的个体（AUC=0.75）和稳定的个体。将 6-12 个月内 MMSE 的变化包括在内，进一步改善了模型（AUC=0.84）。
我们的研究结果表明，将 pNFL 与简单的痴呆筛查（MMSE）相结合，可以可靠地预测 MCI 患者是否有可能在 5 年内进展为 AD 痴呆。
