Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA; Institut Guttman, Universitat Autonoma de Barcelona, Badalona, Barcelona, Spain.
Clin Neurophysiol. 2019 Sep;130(9):1502-1510. doi: 10.1016/j.clinph.2019.04.721. Epub 2019 Jun 21.
In older adults, type-2 diabetes mellitus (T2DM) impacts cognition and increases dementia risk. Prior studies suggest that impaired neuroplasticity may contribute to the cognitive decline in T2DM, but the underlying mechanisms of altered neuroplasticity are unclear. We investigated the relationship of the concentration of glutamatergic metabolites with measures of cortical plasticity in older adults across the spectrum of glucose intolerance/insulin resistance.
Forty adults (50-87 years: 17-T2DM, 14-pre-diabetes, 9-controls) underwent magnetic resonance spectroscopy to quantify glutamate and other key metabolites within a 2 cm region around the hand knob of the left primary motor cortex. Thirty-six also underwent a separate transcranial magnetic stimulation (TMS) assessment of cortical excitability and plasticity using single-pulse TMS and intermittent theta-burst stimulation targeting the same brain region.
Group differences were observed in relative concentrations of glutamine (p = .028), glucose (p = .008), total cholines (p = .048), and the glutamine/glutamate ratio (p = .024). Cortical plasticity was reduced in both T2DM and pre-diabetes groups relative to controls (p-values < .05). Only the T2DM group showed a significant positive association between glutamate concentration and plasticity (r = .56, p = .030).
Neuroplastic mechanisms are already impaired in pre-diabetes. In T2DM, reduced cortico-motor plasticity is associated with lower cortical glutamate concentration.
Impaired plasticity in T2DM is associated with low glutamatergic metabolite levels. The glutamatergic neurotransmission system constitutes a potential therapeutic target for cognitive problems linked to plasticity-related deficiencies in T2DM.
在老年人中，2 型糖尿病（T2DM）会影响认知能力并增加痴呆风险。先前的研究表明，神经可塑性受损可能导致 T2DM 认知能力下降，但神经可塑性改变的潜在机制尚不清楚。我们研究了谷氨酸能代谢物浓度与葡萄糖耐量/胰岛素抵抗谱中老年人大脑皮质可塑性测量值之间的关系。
40 名成年人（50-87 岁：17 名 T2DM、14 名糖尿病前期、9 名对照组）接受磁共振波谱分析，以定量左初级运动皮层手旋钮周围 2cm 区域内的谷氨酸和其他关键代谢物。36 名成年人还接受了单独的经颅磁刺激（TMS）评估，使用单脉冲 TMS 和针对同一脑区的间歇性 theta 爆发刺激来评估皮质兴奋性和可塑性。
组间观察到谷氨酰胺（p=0.028）、葡萄糖（p=0.008）、总胆碱（p=0.048）和谷氨酰胺/谷氨酸比值（p=0.024）的相对浓度存在差异。与对照组相比，T2DM 和糖尿病前期组的皮质可塑性均降低（p 值均<.05）。只有 T2DM 组显示谷氨酸浓度与可塑性之间存在显著正相关（r=0.56，p=0.030）。
糖尿病前期已经存在神经可塑性机制受损。在 T2DM 中，皮质运动可塑性降低与皮质谷氨酸浓度降低相关。
T2DM 中的可塑性受损与谷氨酸能代谢物水平降低有关。谷氨酸能神经传递系统可能成为与 T2DM 中与可塑性相关的缺陷相关的认知问题的治疗靶点。
