Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathology
Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathology
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DOI：
10.1212/01.wnl.0000324925.95210.6d
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发表时间：
2008-09-02
期刊：
影响因子：
9.9
通讯作者：
Haroutunian, V.
中科院分区：
文献类型：
--
作者：
Beeri, M. S.;Schmeidler, J.;Haroutunian, V.
目的：探讨糖尿病治疗与阿尔茨海默病(AD)神经病理的关系。方法：对西奈山医学院脑库的124名糖尿病患者和124名非糖尿病患者进行尸检，研究对象的年龄(平均值=81.2±9.3)、性别(57.3%F)和痴呆严重程度(临床痴呆评分[CDR]2.4+1.7)。在几个新皮质区域以及在海马体、内嗅觉皮质和杏仁体中评估了神经炎性斑块(NPs)和神经原纤维缠结(NFTs)的密度。糖尿病受试者根据其一生服用抗糖尿病药物的记录进行分类：不服用任何抗糖尿病药物(n=29)，仅服用胰岛素(n=49)，服用非胰岛素以外的糖尿病药物(n=28)，或同时使用胰岛素和任何口服降糖药物(n=18)。结果：在5组患者中，内嗅皮层(p=0.003)、杏仁核(p=0.009)和总体NP(p=0.014)以及所有被检查区域的NP计数(p值在0.009到0.04之间)在5组之间存在差异。海马区的NP分级(p=0.057)和联合的新皮质测量(p=0.052)接近有意义。在每一项分析中，伴随用药组的NPs显著少于任何其他相对相似的组(类似于20%)。没有发现显著的NFT差异。结论：本研究的结果表明，胰岛素与其他糖尿病药物的联合使用显著降低了神经炎斑块密度，这与两者对胰岛素神经生物学的影响一致。
Objective: To examine the association between treatment for diabetes and Alzheimer disease (AD) neuropathology.Methods: This postmortem study matched 124 subjects with diabetes to 124 without diabetes from the Mount Sinai School of Medicine Brain Bank, on age (mean = 81.2 + 9.3), sex (57.3% F), and severity of dementia (Clinical Dementia Rating [CDR] 2.4 + 1.7). Densities of neuritic plaques (NPs) and of neurofibrillary tangles (NFTs) were assessed in several neocortical regions and in the hippocampus, entorhinal cortex, and amygdala. Diabetic subjects were classified according to their recorded lifetime antidiabetic medications: none (n = 29), insulin only (n = 49), diabetes medications other than insulin only (n = 28), or concomitant use of both insulin and any oral antidiabetic medications (n = 18). For each dependent variable, analysis of covariance controlling for age at death, sex, and CDR distinguished among the nondiabetic patients and four diabetic subgroups.Results: There were differences among the five groups for NP ratings in the entorhinal cortex (p = 0.003), amygdala (p = 0.009), and overall NP (p = 0.014) as well as counts of NPs in all regions examined (p values ranging from 0.009 to 0.04). NP ratings in the hippocampus (p = 0.057) and the combined neocortical measure (p = 0.052) approached significance. In each analysis, the concomitant medication group had significantly fewer NPs (similar to 20%) than any of the other groups, which were relatively similar. No significant NFT differences were found.Conclusion: The results of this study suggest that the combination of insulin with other diabetes medication is associated with substantially lower neuritic plaque density consistent with the effects of both on the neurobiology of insulin.