Large neutral amino acid changes and delirium in febrile elderly medical patients

A hypothesized but unexplored mechanism for delirium in older persons is that changes in plasma large neutral amino acid (LNAA) concentrations alter brain serotonin levels, result in neurotoxicity, or both. Therefore we performed a prospective study of 21 acutely febrile long-term-care residents to study the relationship between LNAA changes and delirium. Plasma LNAA concentrations were evaluated during illness and 1 month later. Delirium was diagnosed by using the Confusion Assessment Method. Other data included age, body mass index, cognitive impairment, comorbidity, gender, maximum temperature, and medication use. Seven subjects (33%) were delirious during febrile illness. Although the phenylalanine (PHE)/LNAA ratio was higher during illness in both delirious and nondelirious groups, a two-sample t test demonstrated that delirium was associated with a higher illness PHE/LNAA ratio (p = .03). The amount of change in PHE/LNAA from illness to recovery was not different between the delirious and nondelirious groups. Tryptophan/LNAA was not associated with delirium during illness or at recovery. These findings identify another potentially fruitful area of investigation for the prevention and treatment of delirium in older persons.