Clinical Research Branch, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA.
Lancet Neurol. 2011 Feb;10(2):187-98. doi: 10.1016/S1474-4422(10)70277-5. Epub 2010 Dec 10.
Epidemiological, neuropathological, and functional neuroimaging evidence implicates global and regional disruptions in brain metabolism and energetics in the pathogenesis of cognitive impairment. Nerve cell microcircuits are modified by excitatory and inhibitory synaptic activity and neurotrophic factors. Ageing and Alzheimer's disease cause perturbations in cellular energy metabolism, level of excitation or inhibition, and neurotrophic factor release, which overwhelm compensatory mechanisms and result in dysfunction of neuronal microcircuits and brain networks. A prolonged positive energy balance impairs the ability of neurons to adapt to oxidative and metabolic stress. Results from experimental studies in animals show how disruptions caused by chronic positive energy balance, such as diabetes, lead to accelerated cognitive ageing and Alzheimer's disease. Therapeutic interventions to allay cognitive dysfunction that target energy metabolism and adaptive stress responses (such as neurotrophin signalling) have been effective in animal models and in preliminary studies in humans.
流行病学、神经病理学和功能神经影像学证据表明，大脑代谢和能量的整体和区域紊乱与认知障碍的发病机制有关。神经细胞微电路通过兴奋性和抑制性突触活动以及神经营养因子进行修饰。衰老和阿尔茨海默病导致细胞能量代谢、兴奋或抑制水平以及神经营养因子释放的波动，这些波动超过了代偿机制，导致神经元微电路和大脑网络功能障碍。长期的正能平衡会损害神经元适应氧化和代谢应激的能力。动物实验研究的结果表明，慢性正能平衡（如糖尿病）引起的紊乱如何导致认知衰老和阿尔茨海默病的加速发生。针对能量代谢和适应性应激反应（如神经营养因子信号）的治疗干预措施在动物模型和人类初步研究中均有效，可以缓解认知功能障碍。
