Strong Association between Plasma Dipeptidyl Peptidase-4 Activity and Impaired Cognitive Function in Elderly Population with Normal Glucose Tolerance.
Strong Association between Plasma Dipeptidyl Peptidase-4 Activity and Impaired Cognitive Function in Elderly Population with Normal Glucose Tolerance.
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血糖耐量正常的老年人血浆二肽基肽酶 4 活性与认知功能受损之间存在密切关联
DOI：
10.3389/fnagi.2017.00247
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发表时间：
2017
影响因子：
4.8
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Chen B;Zheng T;Qin L;Hu X;Zhang X;Liu Y;Liu H;Qin S;Li G;Li Q
目的：炎症、氧化应激和胰高血糖素样肽-1 (GLP-1) 减少是认知障碍的危险因素。二肽基肽酶-4 (DPP4) 被确定为一种能够增强这些危险因素的新型脂肪因子。因此，我们研究了糖耐量正常（NGT）的中国老年人群血浆DPP4活性与认知功能受损之间的关系。方法：我们利用桂林市 1229 名老年参与者（60 岁或以上）的数据进行了一项横断面研究。测量了所有参与者的血浆 DPP4 活性、氧化应激参数、空腹活性 GLP-1 和炎症标志物。认知功能受损是根据国家老龄化研究所-阿尔茨海默病协会工作组标准诊断的。结果：与最低四分位数的参与者相比，血浆 DPP4 活性较高四分位数的参与者具有较高的 C 反应蛋白 (CRP)、白介素 6 (IL-6)、8-iso-PGF2a、硝基酪氨酸，以及较低的 GLP-1 和蒙特利尔认知评估 (MoCA) 评分 (P < 0.001)。调整混杂因素后，随着 DPP4 四分位数的增加，CRP、IL-6、8-iso-PGF2a、硝基酪氨酸和活性 GLP-1 降低的比值比 (OR) 较高（所有 P < 0.001）。在调整潜在混杂因素后，在最高 DPP4 四分位数中，认知功能受损的风险高于最低四分位数（OR，2.26；95% 置信区间，1.36-3.76）。 DPP4 活性、硝基酪氨酸和 8-iso-PGF2a 水平越高，认知功能受损的风险越高（P < 0.05），但 IL-6、CRP 较高或 GLP-1 较低则不会增加认知功能受损的风险。结论：在患有 NGT 的中国老年人群中，血浆 DPP4 活性与认知功能（主要是执行功能）受损显着且独立相关。这种关联的潜在机制可能部分归因于 DPP4 对氧化应激的影响。血浆 DPP4 活性可能作为预防和治疗认知功能受损的风险生物标志物或治疗靶点。
Objective: Inflammation, oxidative stress, and decreased glucagon-like peptide-1 (GLP-1) are risk factors for cognitive impairment. Dipeptidyl peptidase-4 (DPP4) was identified as a novel adipokine capable of enhancing these risk factors. Hence, we investigated the relationship between plasma DPP4 activity and impaired cognitive function in elderly Chinese population with normal glucose tolerance (NGT). Methods: We performed a cross-sectional study using data from 1229 elderly participants (60 years or older) in Guilin. Plasma DPP4 activity, oxidative stress parameters, fasting active GLP-1, and inflammatory markers were measured in all participants. Impaired cognitive function was diagnosed according to the National Institute on Aging-Alzheimer’s Association workgroups criteria. Results: Participants in the upper quartile of plasma DPP4 activity had higher C-reactive protein (CRP), interleukin-6 (IL-6), 8-iso-PGF2a, nitrotyrosine, and lower GLP-1 and Montreal Cognitive Assessment (MoCA) scores compared with those in the lowest quartile (P < 0.001). The odds ratios (ORs) for increased CRP, IL-6, 8-iso-PGF2a, nitrotyrosine, and decreased active GLP-1 were higher with increasing DPP4 quartiles after adjustment for confounders (all P < 0.001). In the highest DPP4 quartile, impaired cognitive function risk was higher (OR, 2.26; 95% confidence interval, 1.36–3.76) than in the lowest quartile after adjustment for potential confounders. The risk for impaired cognitive function increased more with higher levels of DPP4 activity, nitrotyrosine and 8-iso-PGF2a (P < 0.05), but not with higher IL-6, CRP or lower GLP-1. Conclusion: Plasma DPP4 activity is significantly and independently associated with impaired cognitive function, mainly executive, in elderly Chinese population with NGT. The underlying mechanisms for this association may be partly attributed to the effect of DPP4 on oxidative stress. Plasma DPP4 activity might serve as a risk biomarker or therapeutic target for the prevention and treatment of impaired cognitive function.
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影响因子：
2.6
作者：
Kim SM;Song J;Kim S;Han C;Park MH;Koh Y;Jo SA;Kim YY
通讯作者：
Kim YY
影响因子：
105.7
作者：
Kaduszkiewicz, H;Zimmermann, T;van den Bussche, H
通讯作者：
van den Bussche, H
影响因子：
5.8
作者：
Gault, V. A.;Lennox, R.;Flatt, P. R.
通讯作者：
Flatt, P. R.
影响因子：
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作者：
Petersen, Ronald C.;Roberts, Rosebud O.;Knopman, David S.;Boeve, Bradley F.;Geda, Yonas E.;Ivnik, Robcrt J.;Smith, Glenn E.;Jack, Clifford R., Jr.
通讯作者：
Jack, Clifford R., Jr.
影响因子：
9.3
作者：
Ishibashi Y;Matsui T;Maeda S;Higashimoto Y;Yamagishi S
通讯作者：
Yamagishi S