Growth Differentiation Factor 15 and NT-proBNP as Blood-Based Markers of Vascular Brain Injury and Dementia.
Growth Differentiation Factor 15 and NT-proBNP as Blood-Based Markers of Vascular Brain Injury and Dementia.
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DOI：
10.1161/jaha.119.014659
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发表时间：
2020-10-20
影响因子：
5.4
通讯作者：
Seshadri S
中科院分区：
文献类型：
--
作者：
McGrath ER;Himali JJ;Levy D;Conner SC;DeCarli C;Pase MP;Ninomiya T;Ohara T;Courchesne P;Satizabal CL;Vasan RS;Beiser AS;Seshadri S
GDF15（生长分化因子15）和NT - proBNP （N -末端前B型利钠肽）可能有望作为认知结果的生物标志物，包括痴呆。我们在一个基于社区的队列中确定了这些生物标志物与认知结果的关联。在检查7（1998-2001）时，对无痴呆的Framingham Offspring队列参与者的血浆GDF15 （n=1603）和NT‐proBNP水平（n=1590）（53%的女性，平均年龄68.7岁）进行了测量。研究人员对参与者的偶发性痴呆进行了随访。次要结果包括阿尔茨海默病痴呆、磁共振成像脑结构测量和神经认知表现。在中位11.8年的随访期间，131名参与者患上了痴呆症。在多变量Cox比例风险分析中，较高的循环GDF15与发生全因痴呆和阿尔茨海默病痴呆的风险增加相关（自然对数转化生物标志物值每SD增量的风险比[HR]分别为1.54 [95% CI, 1.22-1.95]和1.37 [95% CI, 1.03-1.81]），而较高的血浆NT - proBNP也与全因痴呆的风险增加相关（HR, 1.32; 95% CI, 1.05-1.65）。GDF15升高与大脑和海马总体积降低、白质高强度体积增大和认知能力下降有关。NT‐proBNP升高与较高的白质高强度体积和较差的认知表现相关。将这两种生物标志物添加到传统的风险因素模型中，可改善痴呆风险分类（净重新分类改善指数，0.25;95% CI, 0.05-0.45）。血浆GDF15和NT‐proBNP升高与磁共振成像显示的血管性脑损伤、较差的神经认知表现和bb0 ~ 60岁人群发生痴呆的风险增加有关。与传统的临床危险因素相比，这两种生物标志物都改善了痴呆症的风险分类，表明它们在预测痴呆症发生方面的潜在价值。
GDF15 (growth differentiation factor 15) and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) may offer promise as biomarkers for cognitive outcomes, including dementia. We determined the association of these biomarkers with cognitive outcomes in a community‐based cohort. Plasma GDF15 (n=1603) and NT‐proBNP levels (n=1590) (53% women; mean age, 68.7 years) were measured in dementia‐free Framingham Offspring cohort participants at examination 7 (1998–2001). Participants were followed up for incident dementia. Secondary outcomes included Alzheimer disease dementia, magnetic resonance imaging structural brain measures, and neurocognitive performance. During a median 11.8‐year follow‐up, 131 participants developed dementia. On multivariable Cox proportional‐hazards analysis, higher circulating GDF15 was associated with an increased risk of incident all‐cause and Alzheimer disease dementia (hazard ratio [HR] per SD increment in natural log‐transformed biomarker value, 1.54 [95% CI, 1.22–1.95] and 1.37 [95% CI, 1.03–1.81], respectively), whereas higher plasma NT‐proBNP was also associated with an increased risk of all‐cause dementia (HR, 1.32; 95% CI, 1.05–1.65). Elevated GDF15 was associated with lower total brain and hippocampal volumes, greater white matter hyperintensity volume, and poorer cognitive performance. Elevated NT‐proBNP was associated with greater white matter hyperintensity volume and poorer cognitive performance. Addition of both biomarkers to a conventional risk factor model improved dementia risk classification (net reclassification improvement index, 0.25; 95% CI, 0.05–0.45). Elevated plasma GDF15 and NT‐proBNP were associated with vascular brain injury on magnetic resonance imaging, poorer neurocognitive performance, and increased risk of incident dementia in individuals aged >60 years. Both biomarkers improved dementia risk classification beyond that of traditional clinical risk factors, indicating their potential value in predicting incident dementia.