Investigating the combination of plasma amyloid-beta and geroscience biomarkers on the incidence of clinically meaningful cognitive decline in older adults.
Investigating the combination of plasma amyloid-beta and geroscience biomarkers on the incidence of clinically meaningful cognitive decline in older adults.
复制标题
研究血浆β-淀粉样蛋白和老年科学生物标志物的组合对老年人临床意义认知能力下降的发生率的影响。
DOI：
10.1007/s11357-022-00554-y
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发表时间：
2022
期刊：
影响因子：
5.6
通讯作者：
MAPT/DSAGroup
中科院分区：
文献类型：
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作者：
Lu,Wan-Hsuan;Giudici,KellyVirecoulon;Morley,JohnE;Guyonnet,Sophie;Parini,Angelo;Aggarwal,Geetika;Nguyen,AndrewD;Li,Yan;Bateman,RandallJ;Vellas,Bruno;deSoutoBarreto,Philipe;MAPT/DSAGroup
我们研究了将核心AD神经病理学指标（血浆淀粉样蛋白β [Aβ]42/40）与炎症、细胞应激和神经退行性变的5种血浆标志物相结合来预测认知能力下降。在多领域阿尔茨海默病预防试验（MAPT）的401名无痴呆症的参与者（中位数[IQR]年龄，76 [73-80]岁）中，28名（7.0%）参与者发展为痴呆症，137名（34.2%）在4年内临床痴呆症评级（CDR）量表恶化。在仅使用血浆Aβ的模型中，随着血浆Aβ水平的每个自然对数单位增加，观察到痴呆事件风险增加10倍（不显著）和CDR恶化风险增加5倍。在预测痴呆和CDR进展方面，合并Aβ +多种血浆生物标志物的模型与单独包括Aβ的模型表现相似。然而，在纳入血浆单核细胞趋化蛋白1（MCP 1）和生长分化因子15（GDF 15）作为协变量后，观察到Aβ模型的复合认知评分（CCS）下降（痴呆的一个代表）性能改善。Aβ、GDF 15和MCP 1异常的受试者与生物标志物正常的受试者相比，CCS下降（认知功能恶化）更高（校正β [95% CI]，-0.21 [-0.35至-0.06]，p= 0.005）。总之，我们的研究发现，除了基本的Aβ模型之外，多生物标志物在预测非痴呆老年人中有临床意义的认知下降方面的附加值有限。然而，通过测量血浆生物标志物对炎症和细胞应激状态与Aβ病理学进行联合评估可能会改善认知能力的评价。
We investigated combining a core AD neuropathology measure (plasma amyloid-beta [Aβ]42/40) with five plasma markers of inflammation, cellular stress, and neurodegeneration to predict cognitive decline. Among 401 participants free of dementia (median [IQR] age, 76 [73–80] years) from the Multidomain Alzheimer Preventive Trial (MAPT), 28 (7.0%) participants developed dementia, and 137 (34.2%) had worsening of clinical dementia rating (CDR) scale over 4 years. In the models utilizing plasma Aβ alone, a tenfold increased risk of incident dementia (nonsignificant) and a fivefold increased risk of worsening CDR were observed as each nature log unit increased in plasma Aβ levels. Models incorporating Aβ plus multiple plasma biomarkers performed similarly to models included Aβ alone in predicting dementia and CDR progression. However, improving Aβ model performance for composite cognitive score (CCS) decline, a proxy of dementia, was observed after including plasma monocyte chemoattractant protein 1 (MCP1) and growth differentiation factor 15 (GDF15) as covariates. Participants with abnormal Aβ, GDF15, and MCP1 presented higher CCS decline (worsening cognitive function) compared to their normal-biomarker counterparts (adjusted β [95% CI], − 0.21 [− 0.35 to − 0.06],p= 0.005). In conclusion, our study found limited added values of multi-biomarkers beyond the basic Aβ models for predicting clinically meaningful cognitive decline among non-demented older adults. However, a combined assessment of inflammatory and cellular stress status with Aβ pathology through measuring plasma biomarkers may improve the evaluation of cognitive performance.