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Symposium on disorders of memory
010  encephalopathy and delirium
  1. A Maclullich

    Author information: Professor Alasdair Maclullich Following undergraduate medical training (including an intercalated BSc in Psychology) at the University of Edinburgh, Alasdair MacLullich completed general medical training and went on to do a PhD on glucocorticoids and cognitive ageing. He was Clinical Lecturer in Geriatric Medicine from 2000 to 2005 and was awarded an MRC Clinician Scientist Fellowship in 2005. He was appointed Professor of Geriatric Medicine at the University of Edinburgh in 2008. His research interests are: 1. Pathophysiology of delirium. These projects are examining the role of aberrant stress responses (eg, sustained high cortisol levels after hip fracture) in patients with delirium. This work involves detailed delirium assessment techniques, biomarker measurement (blood, cerebrospinal fluid, saliva), neuroimaging, and animal models development. 2. Neuropsychology of delirium. Systematic studies of neuropsychological deficits in delirium, including development of novel computerised objective measures of attentional deficits, and measurement of perceptual deficits in delirium. 3. Role of variations in glucocorticoid levels in neuroimaging indices of ageing-related atrophy and white matter disease, and chronic cognitive decline.


Abstract: Delirium is a common and serious acute neuropsychiatric syndrome with core features of inattention and cognitive impairment, and associated features including changes in arousal, altered sleep-wake cycle, and other changes in mental status. Delirium affects 15% of general hospital inpatients and at least 25% of inpatients in geriatrics units. It is independently associated with multiple adverse outcomes including increased length of stay, loss of independence, and increased mortality. Though delirium has consistent core clinical features, it has a very wide range of precipitating factors, including acute illness, surgery, trauma, and drugs. The mechanisms by which these precipitating factors lead to delirium are largely obscure. A basic classification for these diverse aetiological factors can be proposed: (a) direct brain insults and (b) aberrant stress responses. Direct brain insults are largely indiscriminate and include general and regional energy deprivation (eg, hypoxia, hypoglycaemia, stroke), metabolic abnormalities (eg, hyponatraemia, hypercalcaemia), and the effects of drugs. Aberrant stress responses are conceptually and mechanistically distinct from direct brain insults in that they constitute adverse effects of stress-response pathways, which, in health, are adaptive. Two stress response systems likely to be involved in the pathophysiology of delirium are discussed: inflammation and the sickness behaviour response, and activity of the limbic-hypothalamic-pituitary-adrenal axis. The detection of delirium depends on (a) assessment of the patient's mental state, and (b) informant history. Mental status is assessed by a combination of interview and formal cognitive testing. Informant history may also reveal pre-existing cognitive impairment. Delirium may indicate life-threatening illness such as pneumonia, and rapid screening for such conditions is essential. Further assessment involves thorough consideration of potential predisposing and precipitating factors. All variables, which might adversely affect brain function, should be addressed. Thus, as well as treating the presumed proximal cause, oxygenation, hydration and nutrition should be optimised, deliriogenic drugs discontinued, and where possible, predisposing factors ameliorated. Drug treatment for agitation and/or distressing psychotic symptoms, even in the absence of motor hyperactivity, may be required. Delirium, which does not resolve in a few days, may require second-line investigations. Persistent delirium (> 1 month) occurs in around 20% of patients; here other diagnoses such as depression or dementia should also be considered. Delirium commonly co-exists with dementia, and patients with delirium should be screened for this. Delirium is also associated with a higher risk of future dementia, and older patients not meeting criteria for current dementia should be followed up with cognitive assessment.

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