신경인지기능 장애로서 제2형 당뇨병 : 병태생리와 치료적 접근 (Type 2 Diabetes Mellitus as a Neurocognitive Disorder : Pathophysiology and Therapeutic Approach)

서지정보

· 발행기관 : 대한생물치료정신의학회
· 수록지 정보 : 생물치료정신의학 / 20권 / 1호 / 24 ~ 34페이지
· 저자명 : 김지현

초록

Type 2 diabetes mellitus(T2DM) has been known to be a major risk factor for neurocognitive disorders including Alzheimer’s disease and vascular dementia. In this regard, insulin resistance is believed to be the central pathophysiology of T2DM-induced Alzheimer-like neurodegeneration and vascular impairment. Production of advanced glycation endproduct(AGE), excessive oxidative stress and consequent mitochondrial dysfunction, glutamate-related cytotoxicity, amyloid-β(Aβ) deposition, tau hyperphosphorylation, vascular endothelial injury, cytokine-induced inflammatory reactions and other disturbances in neural plasticity can be induced by insulin resistance and its related metabolic aberrations. These combined pathophysiologic mechanisms can result in structural deficits in brain regions including the prefrontal cortex and the hippocampus, which have been found to be related with neurocognitive functional declines in T2DM patients compared with non-T2DM controls. T2DM is also bidirectionally associated with higher prevalence of depression, and comorbid depression is related with a greater risk for development of dementia in T2DM patients. It has been shown that antidiabetic drugs are not just hypoglycemic agents, but also can be neuroprotective and even neurotherapeutic drugs in several preclinical trials. However, clinical results are controversial as yet. Further researches are required to precisely understand the aspect of metabolic brain dysfunction in T2DM and develop therapeutic guidelines for prevention and/or treatment of it.

영어초록

Type 2 diabetes mellitus(T2DM) has been known to be a major risk factor for neurocognitive disorders including Alzheimer’s disease and vascular dementia. In this regard, insulin resistance is believed to be the central pathophysiology of T2DM-induced Alzheimer-like neurodegeneration and vascular impairment. Production of advanced glycation endproduct(AGE), excessive oxidative stress and consequent mitochondrial dysfunction, glutamate-related cytotoxicity, amyloid-β(Aβ) deposition, tau hyperphosphorylation, vascular endothelial injury, cytokine-induced inflammatory reactions and other disturbances in neural plasticity can be induced by insulin resistance and its related metabolic aberrations. These combined pathophysiologic mechanisms can result in structural deficits in brain regions including the prefrontal cortex and the hippocampus, which have been found to be related with neurocognitive functional declines in T2DM patients compared with non-T2DM controls. T2DM is also bidirectionally associated with higher prevalence of depression, and comorbid depression is related with a greater risk for development of dementia in T2DM patients. It has been shown that antidiabetic drugs are not just hypoglycemic agents, but also can be neuroprotective and even neurotherapeutic drugs in several preclinical trials. However, clinical results are controversial as yet. Further researches are required to precisely understand the aspect of metabolic brain dysfunction in T2DM and develop therapeutic guidelines for prevention and/or treatment of it.

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