Humans with Type-2 Diabetes Show Abnormal Long-Term Potentiation-Like Cortical Plasticity Associated with Verbal Learning Deficits.
Humans with Type-2 Diabetes Show Abnormal Long-Term Potentiation-Like Cortical Plasticity Associated with Verbal Learning Deficits.
复制标题
DOI：
10.3233/jad-160505
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Pascual-Leone A
中科院分区：
文献类型：
--
作者：
Fried PJ;Schilberg L;Brem AK;Saxena S;Wong B;Cypess AM;Horton ES;Pascual-Leone A
2型糖尿病（T2DM）加速认知老化，增加阿尔茨海默病的风险。啮齿动物T2DM模型显示与学习和记忆减少相关的突触可塑性改变。患有T2DM的人类也表现出认知缺陷，包括学习和记忆力下降，但这些损伤与神经可塑性机制的疗效之间的关系从未被评估过。我们的主要目的是比较有和没有T2DM的人类皮质可塑性的机制。我们的第二个目标是将可塑性指标与认知的标准指标联系起来。对21例T2DM成人患者和15例人口统计学相似的非糖尿病对照患者进行了一项前瞻性横断面队列研究。通过比较间歇性θ波刺激（iTBS）前后单脉冲经颅磁刺激的运动诱发电位（MEP）幅度，评估初级运动皮层的长时程增强样可塑性。可塑性措施进行了比较组间和相关的神经心理评分。在T2DM中，iTBS诱导的MEP调节显著低于对照组，即使在控制了潜在的混淆后。此外，在T2DM中，iTBS后10分钟MEP的调制与Rey听觉言语学习任务（RAVLT）表现显著相关。T2DM患者表现出异常的皮质运动可塑性，与语言学习能力降低相关。由于iTBS后效和RAVLT都是NMDA受体依赖性指标，因此它们在T2DM中的关系可能反映了NMDA受体疗效的全脑变化。这些发现为T2DM的大脑后果提供了新的机制见解，并为监测大脑健康和评估临床干预措施的有效性提供了可靠的手段。
Type-2 diabetes mellitus (T2DM) accelerates cognitive aging and increases risk of Alzheimer’s disease. Rodent models of T2DM show altered synaptic plasticity associated with reduced learning and memory. Humans with T2DM also show cognitive deficits, including reduced learning and memory, but the relationship of these impairments to the efficacy of neuroplastic mechanisms has never been assessed. Our primary objective was to compare mechanisms of cortical plasticity in humans with and without T2DM. Our secondary objective was to relate plasticity measures to standard measures of cognition. A prospective cross-sectional cohort study was conducted on 21 adults with T2DM and 15 demographically-similar non-diabetic controls. Long-term potentiation-like plasticity was assessed in primary motor cortex by comparing the amplitude of motor evoked potentials (MEPs) from single-pulse transcranial magnetic stimulation before and after intermittent theta-burst stimulation (iTBS). Plasticity measures were compared between groups and related to neuropsychological scores. In T2DM, iTBS-induced modulation of MEPs was significantly less than controls, even after controlling for potential confounds. Furthermore, in T2DM, modulation of MEPs 10-min post-iTBS was significantly correlated with Rey Auditory Verbal Learning Task (RAVLT) performance. Humans with T2DM show abnormal cortico-motor plasticity that is correlated with reduced verbal learning. Since iTBS after-effects and the RAVLT are both NMDA receptor-dependent measures, their relationship in T2DM may reflect brain-wide alterations in the efficacy of NMDA receptors. These findings offer novel mechanistic insights into the brain consequences of T2DM and provide a reliable means to monitor brain health and evaluate the efficacy of clinical interventions.