Department of Neurology, Academic Medical Center, Amsterdam, Netherlands.
Lancet. 2010 Feb 27;375(9716):773-5. doi: 10.1016/S0140-6736(09)61158-2.
Systemic infection and drugs with anticholinergic effects are well-recognised and prevalent risk factors for delirium in elderly people. Experimental findings and neuropathological observations suggest that activation of microglia is pivotal for mediation of the behavioural effects of systemic infections. The microglial response is usually regulated tightly, but defensive features could turn neurotoxic once microglial cells escape from cholinergic inhibition. A self-propelling neuroinflammatory reaction might follow, and this cascade could account for the strong association between delirium and long-term cognitive impairment and even dementia. Here, we propose a hypothetical model, suggesting that poor outcome after delirium can be averted in vulnerable elderly people by use of readily available drugs. Agents that either restore cholinergic control of microglia or directly inhibit neuroinflammation warrant testing in clinical trials.
全身性感染和具有抗胆碱能作用的药物是老年人发生谵妄的公认且常见的危险因素。实验结果和神经病理学观察表明，小胶质细胞的激活对于介导全身性感染的行为影响至关重要。小胶质细胞的反应通常受到严格调节，但一旦小胶质细胞逃脱胆碱能抑制，防御特征就可能变得神经毒性。随后可能会出现自我推进的神经炎症反应，这种级联反应可以解释谵妄与长期认知障碍甚至痴呆之间的强烈关联。在这里，我们提出了一个假设模型，表明在易受伤害的老年人中，可以通过使用现成的药物来避免谵妄后的不良后果。恢复小胶质细胞胆碱能控制或直接抑制神经炎症的药物值得在临床试验中进行测试。
