INTRODUCTION: The most well-studied biomarkers in AD are CSF amyloid beta-42 (Aβ42), tau, p-tau, and the ratio p-tau/Aβ42. The ratiometric measure of p-tau/Aβ42 shows the best diagnostic accuracy, and correlates reliably with metrics of cognition in unimpaired participants. However, no study has examined the impact of the CSF p-tau/Aβ42 ratio in predicting cognitive decline in both healthy and AD individuals in one sample. The goal of this study was to examine whether CSF-based p-tau/Aβ42 predicts changes in global cognitive functioning, episodic memory, and executive functioning over a two-year period in cognitively impaired older adults (CU), and in individuals with Mild Cognitive Impairment (MCI) and Alzheimer′s disease (AD). METHODS: This study involves secondary analysis of data from 1215 older adults available in the Alzheimer′s Disease Neuroimaging Initiative (ADNI). Neuropsychological variables, collected at baseline, 6-month, 12-month, and 24-month follow-ups, included the Preclinical Alzheimer′s Cognitive Composite (PACC) to assess global cognitive functioning, ADNI-MEM to assess episodic memory functioning, and ADNI-EF to assess executive functioning. Linear mixed models were constructed to examine the effect of CSF p-tau/Aβ42, diagnostic group, and change over time (baseline, 6-month, 12-month, and 24-month) on cognitive scores. RESULTS: CSF p-tau/Aβ42 ratios predicted worsening cognitive impairment, both on global cognition and episodic memory in individuals with MCI and AD, but not in CU older adults and predicted decline in executive functioning for all three diagnostic groups. DISCUSSION: Our study, including CU, MCI, and AD individuals, provides evidence for differential cognitive consequences of accumulated AD pathology based on diagnostic groups.

中文翻译：

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p-tau /Aβ42比值与阿尔茨海默氏病，轻度认知障碍和认知障碍的老年人认知下降相关

简介：AD中研究最深入的生物标志物是CSF淀粉样蛋白β-42（Aβ42），tau，p-tau和p-tau /Aβ42之比。p-tau /Aβ42的比例测量显示出最佳的诊断准确性，并且与无障碍参与者的认知指标可靠相关。但是，没有一项研究检查过CSF p-tau /Aβ42比在预测一个样本中健康人和AD个体认知下降方面的影响。这项研究的目的是检查基于CSF的p-tau /Aβ42能否预测认知障碍的老年人（CU）和轻度个体在两年期间的整体认知功能，情节记忆和执行功能的变化认知障碍（MCI）和阿尔茨海默氏病（AD）。方法：这项研究涉及阿尔茨海默氏病神经影像学倡议（ADNI）中1215名老年人的数据的二次分析。在基线，6个月，12个月和24个月的随访中收集的神经心理学变量包括临床前阿尔茨海默氏症认知复合材料（PACC）评估整体认知功能，ADNI-MEM评估情节记忆功能以及ADNI-EF评估执行功能。构建线性混合模型以检查CSF p-tau /Aβ42，诊断组以及随时间（基线，6个月，12个月和24个月）对认知得分的影响。结果：CSF p-tau /Aβ42比值预测了MCI和AD患者的整体认知和情景记忆方面的认知障碍恶化，但不是在CU老年人中，并且预计所有三个诊断组的执行功能都会下降。讨论：我们的研究包括CU，MCI和AD个体，为基于诊断组的累积性AD病理学差异性认知后果提供了证据。