Sierra-Rio Alba, Balasa Mircea, Olives Jaume, Antonell Anna, Iranzo Alex, Castellví Magda, Bosch Beatriz, Grau-Rivera Oriol, Fernandez-Villullas Guadalupe, Rami Lorena, Lladó Albert, Sánchez-Valle Raquel, Molinuevo José Luis
School of Medicine, University of Barcelona, Barcelona, Spain.
Neurodegener Dis. 2016;16(1-2):69-76. doi: 10.1159/000439258. Epub 2015 Nov 12.
Determination of Alzheimer's disease (AD) by cerebrospinal fluid (CSF) biomarkers - 42-amino-acid amyloid-β (Aβ42), total tau and phosphorylated tau (p-tau) - has demonstrated high validity for detecting AD neuropathological changes. However, their prognostic utility to predict the onset of dementia in predementia subjects is still questioned. We aimed to study the prospective clinical evolution of a group of subjects with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) and to determine the prognostic capacity of AD CSF biomarkers.
149 subjects with MCI or SCD, not meeting dementia criteria, underwent a prospective clinical, neuropsychological and CSF biomarker study. Patients were initially classified as SCD or MCI following internationally accepted criteria. CSF sampling was obtained and analysed following consensus protocols. Neuropsychological and clinical evaluations were conducted at the follow-up. Statistical analysis considering the final clinical diagnosis, regression analysis to define risk factors and survival curves for progression were made.
72.4% of subjects (83% MCI and 27% SCD) with a pathological CSF ratio (Aβ42/p-tau) met criteria for dementia during the 5-year follow-up versus 18.7% of subjects from the group with a normal ratio. The pathological CSF ratio was a powerful marker of risk for AD dementia (OR 27.1; 95% CI 10.3-71.2). Kaplan-Meier survival curves showed that only 15% of subjects with a pathological CSF ratio remained free of AD dementia at 5 years of follow-up. All subjects who reverted to normal cognition presented a normal CSF profile at baseline.
An abnormal AD CSF biomarker profile in predementia subjects is a powerful predictor of cognitive and/or functional decline in the medium term.
通过脑脊液（CSF）生物标志物——42个氨基酸的淀粉样β蛋白（Aβ42）、总tau蛋白和磷酸化tau蛋白（p-tau）来诊断阿尔茨海默病（AD），已证明在检测AD神经病理变化方面具有很高的有效性。然而，它们在预测轻度认知障碍（MCI）患者痴呆症发作方面的预后效用仍受到质疑。我们旨在研究一组主观认知下降（SCD）或MCI患者的前瞻性临床演变情况，并确定AD脑脊液生物标志物的预后能力。
149名不符合痴呆症标准的MCI或SCD患者接受了前瞻性临床、神经心理学和脑脊液生物标志物研究。根据国际公认标准，患者最初被分类为SCD或MCI。按照共识方案采集并分析脑脊液样本。在随访时进行神经心理学和临床评估。进行了考虑最终临床诊断的统计分析、定义风险因素的回归分析以及进展的生存曲线分析。
在5年随访期间，脑脊液比率（Aβ42/p-tau）异常的受试者中有72.4%（MCI患者占83%，SCD患者占27%）符合痴呆症标准，而比率正常组的这一比例为18.7%。脑脊液比率异常是AD痴呆风险的有力标志物（比值比27.1；95%置信区间10.3 - 71.2）。Kaplan-Meier生存曲线显示，在5年随访时，脑脊液比率异常的受试者中只有15%未患AD痴呆症。所有恢复正常认知的受试者在基线时脑脊液指标均正常。
轻度认知障碍患者脑脊液AD生物标志物异常是中期认知和/或功能下降的有力预测指标。
