Pathophysiology of cognitive dysfunction in older people with type 2 diabetes: vascular changes or neurodegeneration?
Pathophysiology of cognitive dysfunction in older people with type 2 diabetes: vascular changes or neurodegeneration?
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DOI：
10.1093/ageing/afp211
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发表时间：
2010
期刊：
影响因子：
6.7
通讯作者：
H. Umegaki
中科院分区：
文献类型：
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作者：
H. Umegaki
最近的研究表明，2 型糖尿病 (T2DM) 是认知功能障碍或痴呆症的危险因素，尤其是与阿尔茨海默病 (AD) 相关的认知功能障碍或痴呆症。基础研究表明，胰岛素通过影响β淀粉样蛋白（Abeta）来加速阿尔茨海默病相关的病理过程。然而，几项尸检样本病理学研究表明，患有糖尿病的痴呆受试者比没有糖尿病的受试者具有更少的 AD 相关神经病理学特征。我们和其他人已经报道，小血管疾病影响老年糖尿病患者的认知功能。 T2DM受试者的无症状缺血性病变可能会降低发生痴呆的阈值，这可能解释了基础研究和临床病理学研究之间的不一致。使用淀粉样蛋白成像和磁共振成像对没有明显痴呆的 T2DM 受试者进行纵向随访可能会阐明这些问题。追踪直至出现明显的痴呆症，使得可以比较痴呆症发生前后的淀粉样蛋白负荷和缺血性病变。此外，对患有或不患有胰岛素抵抗的非痴呆老年人进行淀粉样蛋白成像，将验证胰岛素在 Abeta 加工和沉积中的作用。血管危险因素可能代表治疗目标，而神经退行性疾病尚未适合治疗。针对血管危险因素的医疗干预是否对痴呆症的发生和进展具有保护作用仍有待研究。
Recent studies have revealed that type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction or dementia, especially those related to Alzheimer's disease (AD). Basic research suggests that insulin accelerates Alzheimer-related pathology through its effects on the amyloid beta (Abeta). Several pathological studies with autopsy samples have demonstrated, however, that dementia subjects with diabetes have less AD-related neuropathology than subjects without diabetes. We and others have reported that small vessel diseases affect cognitive function in older diabetics. Asymptomatic ischemic lesions in T2DM subjects may lower the threshold for the development of dementia and this may explain the inconsistency between the basic research and clinicopathological studies. Longitudinal follow-up of T2DM subjects without overt dementia using both amyloid imaging and magnetic resonance imaging may elucidate these issues. Following up until the development of overt dementia would make it possible to compare both amyloid load and ischemic lesions before and after the development of dementia. Moreover, amyloid imaging in non-demented older people with or without insulin resistance would verify the role of insulin in the processing and deposition of Abeta. Vascular risk factors may represent a therapeutic target, while neurodegenerative pathologies have not yet been amenable to treatment. It remains to be investigated whether medical interventions on vascular risk factors have protective effects against the development and progress of dementia.