Pathophysiology of cognitive dysfunction in older people with type 2 diabetes: vascular changes or neurodegeneration?

摘要

Recent studies have revealed that type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction or dementia,nespecially those related to Alzheimer’s disease (AD). Basic research suggests that insulin accelerates Alzheimer-related pathologynthrough its effects on the amyloid beta (Aβ). Several pathological studies with autopsy samples have demonstrated,nhowever, that dementia subjects with diabetes have less AD-related neuropathology than subjects without diabetes. We andnothers have reported that small vessel diseases affect cognitive function in older diabetics. Asymptomatic ischemic lesions innT2DM subjects may lower the threshold for the development of dementia and this may explain the inconsistency betweennthe basic research and clinicopathological studies. Longitudinal follow-up of T2DM subjects without overt dementia usingnboth amyloid imaging and magnetic resonance imaging may elucidate these issues. Following up until the development ofnovert dementia would make it possible to compare both amyloid load and ischemic lesions before and after the developmentnof dementia. Moreover, amyloid imaging in non-demented older people with or without insulin resistance would verify thenrole of insulin in the processing and deposition of Aβ. Vascular risk factors may represent a therapeutic target, while neurodegenerativenpathologies have not yet been amenable to treatment. It remains to be investigated whether medicalninterventions on vascular risk factors have protective effects against the development and progress of dementia.