As yet, detailed neuropathological studies on delirium are lacking [53-55], and consequently the current neurobiological understanding of the pathogenesis of delirium is based largely on correlative clinico-biochemical studies. The pathophysiological link between delirium and a broad array of precipitating factors remains difficult to establish as most of these conditions occur without identifiable involvement of the brain (Table 7.5). Despite the uncertainty on how different etiological causes may evoke similar symptoms, it is thought that a common feature in delirium is the acute and transient impairment in homeostatic balance of the central nervous system (CNS) comparable to the concepts of renal or hepatic insufficiency. There is clinical and neuropathological evidence suggesting that preexisting dementia significantly increases susceptibility of the CNS to deleterious effects of acute insults . Synaptic disconnection may be a major contributor to delirium risk, together with other aspects of dementia, such as microglial activation and chronic hypocholiner- gic function.