Growth differentiation factor-15 and white matter hyperintensities in cognitive impairment and dementia.
Growth differentiation factor-15 and white matter hyperintensities in cognitive impairment and dementia.
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DOI：
10.1097/md.0000000000004566
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发表时间：
2016-08
期刊：
影响因子：
1.6
通讯作者：
Chen CP
中科院分区：
文献类型：
--
作者：
Chai YL;Hilal S;Chong JPC;Ng YX;Liew OW;Xu X;Ikram MK;Venketasubramanian N;Richards AM;Lai MKP;Chen CP
文本中提供补充数字内容血管病理学在认知能力下降和痴呆症的发展中发挥着重要作用。在这种情况下，生长分化因子-15（GDF-15）由于其在组织损伤期间的炎症和营养反应中的调节作用而被认为是生物标志物。然而，关于GDF-15与脑血管疾病（CeVD）负担或认知障碍谱的相关性的数据有限。因此，我们的目的是研究外周水平的GDF-15的认知功能障碍无痴呆（CIND）或阿尔茨海默病（AD）的受试者评估CeVD使用病例对照队列设计，从记忆诊所和记忆诊所和社区招募病例和对照。所有受试者均接受详细的神经心理学评估、3特斯拉磁共振成像和静脉抽血。根据临床标准将受试者分类为CIND或AD，而显著CeVD定义为存在皮质梗死和/或2个或2个以上腔隙，和/或2个或2个以上脑区融合性白色高信号（WMH）。共有324例受试者入选本研究，其中80例无认知功能障碍，144例CIND，100例AD。较高的GDF-15水平与疾病组显著相关，尤其是在存在CeVD的情况下，即CIND伴CeVD（比值比[OR]：7.21; 95%置信区间[CI]：2.14-24.27）和AD伴CeVD（OR：21.87; 95% CI：2.01-237.43）。在不同的CeVD标志物中，仅WMH与较高的GDF-15水平相关（OR：3.97; 95% CI：1.79-8.83）。排除心血管疾病受试者后，GDF-15与认知障碍以及WMH之间的相关性仍然显着。总之，我们表明GDF-15增加可能是WMH受试者中CIND和AD的生物标志物。
Supplemental Digital Content is available in the text Vascular pathology plays an important role in the development of cognitive decline and dementia. In this context, growth differentiation factor-15 (GDF-15) has been suggested to be a biomarker due to its regulatory roles in inflammatory and trophic responses during tissue injury. However, limited data exist on the associations of GDF-15 with either cerebrovascular disease (CeVD) burden or the spectrum of cognitive impairment. Therefore, we aimed to study peripheral levels of GDF-15 incognitive impairment no dementia (CIND) or Alzheimer disease (AD) subjects assessed for CeVD using a case–control cohort design, with cases recruited from memory clinics and controls from memory clinics and the community. All subjects underwent detailed neuropsychological assessment, 3-Tesla magnetic resonance imaging, and venous blood draw. Subjects were classified as CIND or AD based on clinical criteria, while significant CeVD was defined as the presence of cortical infarcts and/or 2 lacunes or more, and/or confluent white matter hyperintensities (WMHs) in 2 or more brain regions. A total of 324 subjects were included in the study, of whom 80 had no cognitive impairment, 144 CIND and 100with AD. Higher GDF-15 levels were significantly associated with disease groups, especially in the presence of CeVD, namely, CIND with CeVD (odds ratios [OR]: 7.21; 95% confidence interval [CI]: 2.14–24.27) and AD with CeVD (OR: 21.87; 95% CI: 2.01–237.43). Among the different CeVD markers, only WMH was associated with higher GDF-15 levels (OR: 3.97; 95% CI: 1.79–8.83). The associations between GDF-15 and cognitive impairment as well as with WMH remained significant after excluding subjects with cardiovascular diseases. In conclusion, we showed that increased GDF-15 may be a biomarker for CIND and AD in subjects with WMH.