School of Biochemistry and Immunology and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin 2, Republic of Ireland.
Biochem Soc Trans. 2011 Aug;39(4):945-53. doi: 10.1042/BST0390945.
It is widely accepted that inflammation plays some role in the progression of chronic neurodegenerative diseases such as AD (Alzheimer's disease), but its precise role remains elusive. It has been known for many years that systemic inflammatory insults can signal to the brain to induce changes in CNS (central nervous system) function, typically grouped under the syndrome of sickness behaviour. These changes are mediated via systemic and CNS cytokine and prostaglandin synthesis. When patients with dementia suffer similar systemic inflammatory insults, delirium is a frequent consequence. This profound and acute exacerbation of cognitive dysfunction is associated with poor prognosis: accelerating cognitive decline and shortening time to permanent institutionalization and death. Therefore a better understanding of how delirium occurs during dementia and how these episodes impact on existing neurodegeneration are now important priorities. The current review summarizes the relationship between dementia, systemic inflammation and episodes of delirium and addresses the basic scientific approaches currently being pursued with respect to understanding acute cognitive dysfunction during aging and dementia. In addition, despite there being limited studies on this subject, it is becoming increasingly clear that infections and other systemic inflammatory conditions do increase the risk of AD and accelerate the progression of established dementia. These data suggest that systemic inflammation is a major contributor to the progression of dementia and constitutes an important clinical target.
人们普遍认为,炎症在慢性神经退行性疾病(如 AD(阿尔茨海默病))的进展中起着一定的作用,但它的确切作用仍不清楚。多年来,人们已经知道全身性炎症刺激可以向大脑发出信号,诱导中枢神经系统(CNS)功能发生变化,通常被归类为疾病行为综合征。这些变化是通过全身和 CNS 细胞因子和前列腺素合成介导的。当痴呆患者遭受类似的全身性炎症刺激时,谵妄是常见的后果。这种认知功能严重而急性恶化与预后不良有关:加速认知衰退并缩短永久住院和死亡的时间。因此,更好地了解痴呆期间谵妄的发生方式以及这些发作如何影响现有的神经退行性变,现在是重要的优先事项。目前的综述总结了痴呆、全身性炎症和谵妄发作之间的关系,并探讨了目前正在研究的理解衰老和痴呆期间急性认知功能障碍的基本科学方法。此外,尽管针对这一主题的研究有限,但越来越明显的是,感染和其他全身性炎症状况确实会增加 AD 的风险并加速已确立的痴呆的进展。这些数据表明,全身性炎症是痴呆进展的主要原因,并构成了一个重要的临床目标。