Alzheimer's disease and type 2 diabetes mellitus are distinct diseases with potential overlapping metabolic dysfunction upstream of observed cognitive decline.
Alzheimer's disease and type 2 diabetes mellitus are distinct diseases with potential overlapping metabolic dysfunction upstream of observed cognitive decline.
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DOI：
10.1111/bpa.12655
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发表时间：
2019-01
期刊：
影响因子：
--
通讯作者：
Nelson PT
中科院分区：
文献类型：
--
作者：
Chornenkyy Y;Wang WX;Wei A;Nelson PT
阿尔茨海默病(AD)和2型糖尿病(T2 DM)是与衰老相关的疾病，发病率和死亡率都很高。在人类和动物模型中的一些发现已经将T2 DM与AD类型的痴呆联系起来。尽管2型糖尿病与认知功能障碍之间存在流行病学联系，但两者之间的相互关系机制尚不清楚。在尸检证实的纵向研究中，证据的优势表明血管机制，而不是经典的AD类型的病理，是自我报告的T2 DM患者经常出现的认知功能下降的基础。T2 DM是心脑血管疾病(CVD)的已知风险因素，包括脑和其他器官中脑梗塞和小血管疾病的风险增加。此外，死后大脑的神经病理学检查显示有脑血管疾病的证据，T2 DM与β-淀粉样沉积或神经原纤维缠结几乎没有相关性。然而，早期AD特异性病理的上游机制仍然不清楚。在这一点上，T2 DM/“代谢综合征”和AD的病理机制可能确实存在重叠。更具体地说，早期AD患者的大脑胰岛素处理、葡萄糖代谢、线粒体功能和/或脂代谢可能发生改变，并直接影响症状和/或神经病理学。
Alzheimer’s disease (AD) and type-2 diabetes mellitus (T2DM) are highly prevalent aging-related diseases associated with significant morbidity and mortality. Some findings in human and animal models have linked T2DM to AD-type dementia. Despite epidemiological associations between the T2DM and cognitive impairment, the inter-relational mechanisms are unclear. The preponderance of evidence in longitudinal studies with autopsy confirmation have indicated that vascular mechanisms, rather than classic AD-type pathologies, underlie the cognitive decline often seen in self-reported T2DM. T2DM is a known risk factor for cardiovascular and cerebrovascular disease (CVD), including increased risk of infarcts and small vessel disease in the brain and other organs. Furthermore, neuropathological examinations of post-mortem brains demonstrated evidence of cerebrovascular disease and little to no correlation between T2DM and β-amyloid deposits or neurofibrillary tangles. Nevertheless, the mechanisms upstream of early AD-specific pathology remain obscure. In this regard, there may indeed be overlap between the pathologic mechanisms of T2DM/”metabolic syndrome”, and AD. More specifically, cerebral insulin processing, glucose metabolism, mitochondrial function, and/or lipid metabolism could be altered in patients in early AD and directly influence symptomatology and/or neuropathology.
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DOI：
10.1038/nrneurol.2017.185
发表时间：
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期刊：
Nature reviews. Neurology
影响因子：
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