Alzheimer's Disease Biomarkers and Future Decline in Cognitive Normal Older Adults
Alzheimer's Disease Biomarkers and Future Decline in Cognitive Normal Older Adults
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DOI：
10.3233/jad-170511
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发表时间：
2017-01-01
影响因子：
4
通讯作者：
Gomez-Isla, Teresa
中科院分区：
文献类型：
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作者：
Dumurgier, Julien;Hanseeuw, Bernard J.;Gomez-Isla, Teresa
工作背景：随着阿尔茨海默病（AD）改良疗法向临床前阶段发展，识别有认知能力下降风险的老年人是一项挑战。目的：在一组认知功能完好的老年人中研究AD生物标志物与随后认知变化之间的关系。84名认知正常的受试者（平均年龄72.0岁，通过马萨诸塞州阿尔茨海默病研究中心和哈佛衰老脑研究招募了59%的女性），并随访3年以上。在所有病例中，在进入研究时，可测量脑脊液（CSF）中淀粉样蛋白β 1-42（A β（42））、总Tau（t-Tau）和苏氨酸181磷酸化Tau（p-Tau 181）。大多数参与者的基线脑MRI、FDG-PET和PiB-PET数据可用。基线AD生物标志物和认知纵向变化之间的关系进行了评估，使用考克斯比例风险回归和线性混合models.Results：14%的参与者增加了他们的全球临床痴呆评级（CDR）评分从0到0.5在随访期间。CDR评分增加与较高的基线CSF t-Tau和p-Tau 181、较高的整体皮质PiB保留和较低的海马体积相关。高CSF t-Tau和低A β（42）或低海马体积的组合与认知结果的相关性比每个单一生物标志物更强。更高的CSF t-Tau是唯一的生物标志物与随后的MMSE score.Conclusions下降：基线CSF t-Tau和p-Tau 181，在体内淀粉样蛋白负荷，海马体积都独立与未来的认知下降。然而，这些生物标志物预测认知能力下降风险的区分能力是有限的。
Background: Identifying older adults at risk of cognitive decline represents a challenge as Alzheimer's disease (AD) modifying therapies move toward preclinical stages.Objective: To investigate the relationship between AD biomarkers and subsequent change in cognition in a cohort of cognitively intact older adults.Methods: 84 cognitively normal subjects (mean age 72.0 years, 59% women) were recruited through the Massachusetts Alzheimer's Disease Research Center and the Harvard Aging Brain Study and followed over 3 years. Measurements of amyloid-beta 1-42 (A beta(42)), total Tau (t-Tau), and Tau phosphorylated at threonine 181 (p-Tau181) in the cerebrospinal fluid (CSF) at study entry were available in all cases. Baseline brain MRI, FDG-PET, and PiB-PET data were available in the majority of participants. Relationship between baseline AD biomarkers and longitudinal change in cognition was assessed using Cox proportional hazard regression and linear mixed models.Results: 14% participants increased their global Clinical Dementia Rating (CDR) score from 0 to 0.5 during follow-up. A CDR score increase was associated with higher baseline CSF t-Tau and p-Tau181, higher global cortical PiB retention, and lower hippocampal volume. The combination of high CSF t-Tau and low A beta(42) or low hippocampal volume was more strongly related to cognitive outcome than each single biomarker. Higher CSF t-Tau was the only biomarker associated with subsequent decline in MMSE score.Conclusions: Baseline CSF t-Tau and p-Tau181, in vivo amyloid load, and hippocampal volume were all independently associated with future decline in cognition. The discriminatory ability of these biomarkers to predict risk of cognitive decline, however, was only modest.