Brain insulin resistance deteriorates cognition by altering the topological features of brain networks.
Brain insulin resistance deteriorates cognition by altering the topological features of brain networks.
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大脑胰岛素抵抗通过改变大脑网络的拓扑特征来恶化认知能力
DOI：
10.1016/j.nicl.2016.12.009
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发表时间：
2017
影响因子：
4.2
通讯作者：
Bai, Feng
中科院分区：
文献类型：
--
作者：
Su, Fan;Shu, Hao;Ye, Qing;Wang, Zan;Xie, Chunming;Yuan, Baoyu;Zhang, Zhijun;Bai, Feng
胰岛素抵抗是2型糖尿病（T2 D）和阿尔茨海默病（AD）之间联系的潜在机制之一，我们基于基于路径的遗传关联分析探讨了其与认知相关的体内神经生物学。87名轻度认知功能障碍（MCI）受试者和135名匹配的对照者（HC）在基线时接受功能MRI扫描、临床评价和20个脑胰岛素抵抗相关基因的外显子测序。进行了平均35个月的纵向研究，以评估他们随着时间的推移认知能力的下降。通过使用认知作为表型，我们检测了修饰认知障碍的基因，包括AKT 2，PIK 3CB，IGF 1 R，PIK 3CD，MTOR，IDE，AKT 1 S1和AKT 1。基于这些位点，利用质量单变量建模来构建功能网络。MCI显示主要在小脑-额-颞区的断开，而补偿可能发生在额-顶区，以维持整体网络效率。此外，该网络的行为意义也得到了强调，因为内侧颞叶和前额叶皮层的拓扑特征部分地决定了纵向认知能力的下降。我们的研究结果表明，胰岛素活性的恢复是一个有前途的治疗目标，以减轻与T2 D和AD相关的认知功能下降。脑胰岛素抵抗的遗传变异影响认知。胰岛素通路改变脑网络的拓扑特征。大脑整体效率预测了认知随时间的变化。减轻大脑胰岛素抵抗可能会缓解认知能力下降。
Insulin resistance represents one of the mechanisms underlying the link between type 2 diabetes (T2D) and Alzheimer's disease (AD), and we explored its in vivo neurobiology related to cognition based on a pathway-based genetic association analyses. Eighty-seven mild cognitive impairment (MCIs) subjects and 135 matched controls (HCs) were employed at baseline, and they underwent functional MRI scans, clinical evaluations and exon sequencings of 20 genes related to brain insulin resistance. A longitudinal study for an average of 35 months was performed to assess their cognitive decline over time. By using cognition as the phenotype, we detected genes that modified cognitive impairments, including AKT2, PIK3CB, IGF1R, PIK3CD, MTOR, IDE, AKT1S1 and AKT1. Based on these loci, the mass univariate modeling was utilized to construct the functional network. The MCIs showed disconnections mainly in the cerebellum-frontal-temporal regions, while compensations may occur in frontal-parietal regions to maintain the overall network efficiency. Moreover, the behavioral significance of the network was highlighted, as topological characteristics of the medial temporal lobe and the prefrontal cortex partially determine longitudinal cognitive decline. Our results suggested that the restoration of insulin activity represents a promising therapeutic target for alleviating cognitive decline associated with T2D and AD. Genetic variations of brain insulin resistance influence cognition. Insulin pathway modifies the topological characteristics of brain networks. Brain overall efficiency predicts the cognitive changes over time. Relieving brain insulin resistance may alleviate cognitive declines.
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影响因子：
7.8
作者：
Pawlikowska L;Hu D;Huntsman S;Sung A;Chu C;Chen J;Joyner AH;Schork NJ;Hsueh WC;Reiner AP;Psaty BM;Atzmon G;Barzilai N;Cummings SR;Browner WS;Kwok PY;Ziv E;Study of Osteoporotic Fractures
通讯作者：
Study of Osteoporotic Fractures
DOI：
10.1016/j.jalz.2011.03.005
发表时间：
2011-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
McKhann GM;Knopman DS;Chertkow H;Hyman BT;Jack CR Jr;Kawas CH;Klunk WE;Koroshetz WJ;Manly JJ;Mayeux R;Mohs RC;Morris JC;Rossor MN;Scheltens P;Carrillo MC;Thies B;Weintraub S;Phelps CH
通讯作者：
Phelps CH
影响因子：
5.7
作者：
Rao SM;Bonner-Jackson A;Nielson KA;Seidenberg M;Smith JC;Woodard JL;Durgerian S
通讯作者：
Durgerian S
影响因子：
2.4
作者：
Garcia, J.;Ahmadi, A.;Marcusson, J.
通讯作者：
Marcusson, J.
影响因子：
--
作者：
Biffi, Alessandro;Anderson, Christopher D.;Desikan, Rahul S.;Sabuncu, Mert;Cortellini, Lynelle;Schmansky, Nick;Salat, David;Rosand, Jonathan
通讯作者：
Rosand, Jonathan