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阿尔茨海默病与2型糖尿病相关的认知障碍:关联及一种假说。

Alzheimer disease and cognitive impairment associated with diabetes mellitus type 2: associations and a hypothesis.

作者信息

Domínguez R O, Pagano M A, Marschoff E R, González S E, Repetto M G, Serra J A

机构信息

Departamento de Neurología, Hospital Sirio Libanés, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.

Departamento de Neurología, Hospital Juan A. Fernández, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.

出版信息

Neurologia. 2014 Nov-Dec;29(9):567-72. doi: 10.1016/j.nrl.2013.05.006. Epub 2013 Oct 18.

Abstract

INTRODUCTION

Epidemiological studies have demonstrated that patients with diabetes mellitus have an increased risk of developing Alzheimer disease, but the relationship between the 2 entities is not clear.

DEVELOPMENT

Both diseases exhibit similar metabolic abnormalities: disordered glucose metabolism, abnormal insulin receptor signalling and insulin resistance, oxidative stress, and structural abnormalities in proteins and β-amyloid deposits. Different hypotheses have emerged from experimental work in the last two decades. One of the most comprehensive relates the microvascular damage in diabetic polyneuritis with the central nervous system changes occurring in Alzheimer disease. Another hypothesis considers that cognitive impairment in both diabetes and Alzheimer disease is linked to a state of systemic oxidative stress. Recently, attenuation of cognitive impairment and normalisation of values in biochemical markers for oxidative stress were found in patients with Alzheimer disease and concomitant diabetes. Antidiabetic drugs may have a beneficial effect on glycolysis and its end products, and on other metabolic alterations.

CONCLUSIONS

Diabetic patients are at increased risk for developing Alzheimer disease, but paradoxically, their biochemical alterations and cognitive impairment are less pronounced than in groups of dementia patients without diabetes. A deeper understanding of interactions between the pathogenic processes of both entities may lead to new therapeutic strategies that would slow or halt the progression of impairment.

摘要

引言

流行病学研究表明,糖尿病患者患阿尔茨海默病的风险增加,但这两种疾病之间的关系尚不清楚。

进展

两种疾病都表现出相似的代谢异常:葡萄糖代谢紊乱、胰岛素受体信号传导异常和胰岛素抵抗、氧化应激以及蛋白质和β-淀粉样蛋白沉积的结构异常。在过去二十年的实验研究中出现了不同的假说。其中最全面的一种假说是将糖尿病性多发性神经炎中的微血管损伤与阿尔茨海默病中发生的中枢神经系统变化联系起来。另一种假说认为,糖尿病和阿尔茨海默病中的认知障碍都与全身氧化应激状态有关。最近,在患有阿尔茨海默病和合并糖尿病的患者中发现认知障碍有所减轻,氧化应激生化标志物的值也恢复正常。抗糖尿病药物可能对糖酵解及其终产物以及其他代谢改变有有益作用。

结论

糖尿病患者患阿尔茨海默病的风险增加,但矛盾的是,他们的生化改变和认知障碍比无糖尿病的痴呆患者组要轻。对这两种疾病致病过程之间相互作用的更深入理解可能会带来新的治疗策略,从而减缓或阻止损伤的进展。

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