Systemic infection and delirium: when cytokines and acetylcholine collide.
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.
van Gool
Willem A
WA
Department of Neurology, Academic Medical Center, Amsterdam, Netherlands. w.a.vangool@amc.uva.nl
van de Beek
Diederik
D
Eikelenboom
Piet
P
D000109:Acetylcholine / Q000502:physiology*; D000368:Aged; D018678:Cholinergic Agents / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000009:adverse effects* / Q000494:pharmacology; D016207:Cytokines / Q000502:physiology*; D003693:Delirium / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000209:etiology*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D011930:Reaction Time / Q000187:drug effects; D012307:Risk Factors; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D013028:Space Perception / Q000187:drug effects; D013850:Thinking / Q000187:drug effects
D018678:Cholinergic Agents; D018680:Cholinergic Antagonists; D016207:Cytokines; D000109:Acetylcholine