Grossman Hillel
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, USA.
CNS Spectr. 2003 Nov;8(11):815-23. doi: 10.1017/s1092852900019258.
Diabetes mellitus has long been considered a risk factor for the development of vascular dementia. Epidemiologic evidence has suggested that diabetes mellitus significantly increases risk for the development of Alzheimer's disease, independent of vascular risk factors. As insulin's role as a neuromodulator in the brain has been described, its significance for AD has also emerged. Insulin dysregulation may contribute to AD pathology through several mechanisms including decreased cortical glucose utilization particularly in the hippocampus and entorhinal cortex; increased oxidative stress through the formation of advanced glycation end-products; increased Tau phosphorylation and neurofibrillary tangle formation; increased b-amyloid aggregation through inhibition of insulin-degrading enzyme. Future treatment of AD might involve pharmacologic and dietary manipulations of insulin and glucose regulation.
长期以来，糖尿病一直被视为血管性痴呆发生的一个危险因素。流行病学证据表明，糖尿病会显著增加患阿尔茨海默病的风险，且独立于血管危险因素。随着胰岛素作为大脑中神经调节剂的作用被描述，其对阿尔茨海默病的重要性也显现出来。胰岛素调节异常可能通过多种机制导致阿尔茨海默病病理改变，包括皮质葡萄糖利用减少，尤其是在海马体和内嗅皮质；通过晚期糖基化终产物的形成增加氧化应激；增加tau蛋白磷酸化和神经纤维缠结的形成；通过抑制胰岛素降解酶增加β-淀粉样蛋白聚集。未来阿尔茨海默病的治疗可能涉及对胰岛素和葡萄糖调节的药物及饮食干预。
