Free radicals in the pathogenesis of delirium
The aim of this thesis was to look for evidence of increased serum free radical activity in elderly hospital patients with delirium. The following parameters were measured: serum iron, copper, zinc, ascorbic acid, antioxidant activity and markers of lipid peroxidation. The results did not show evidence of increased free radical activity in patients with delirium compared to non-delirious control patients. However, the results did show that, compared to healthy community controls, inpatients with infection and delirium (Group A), or with infection only (Group C) or (unexpectedly) with delirium but without clinical or microbiological evidence of infection (Group D) showed biochemical evidence of a systemic inflammatory response. The pattern of change observed in the inpatient groups was: a reduced serum iron and transferrin saturation, reduced serum zinc, elevated serum copper and reduced plasma ascorbic acid. This pattern of change is associated with inflammation. As a result of these findings, the hypothesis is proposed that delirium represents an epiphenomenon of the systematic inflammatory response syndrome (SIRS). Reduced iron levels, reduced zinc levels and low ascorbic acid levels have all, separately, been associated with altered brain function or cognitive impairment in studies of non-inflammatory states. It is therefore argued that these biochemical changes, individually or in combination with other biochemical and immunological changes that occur during the SIRS, such as HPA axis dysfunction, may result in cognitive impairment during inflammation, and, in severe or predisposing cases, contribution to the clinical manifestation of delirium. It is suggested that the area of the brain most vulnerable to the effects of these changes and, in consequence, most likely to produce cognitive dysfunction during delirium is the limbic system and, in particular, the thalamus, hypothalamus and hippocampus.