Correlations between agitation and other neuropsychiatric symptoms in each stage of Alzheimer's disease: A re-analysis of CATIE-AD

BackgroundAmong neuropsychiatric symptoms (NPSs) of Alzheimer's disease (AD), agitation has been shown to occur commonly in the course of AD, overlapping or comorbid with other NPSs.ObjectiveThe proportion of patients with agitation and the severity of agitation appear to differ depending on the neurocognitive stage of AD, and knowledge about the characteristic comorbid symptom pattern may help in elucidation of the underlying mechanism.MethodsAmong 421 clinic-based patients with AD, we re-analyzed the dataset of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) to examine the correlations between the scores for agitation and those for other Neuropsychiatric Inventory subscales in each neurocognitive stage of AD (mild, moderate, and severe) classified according to scores in Mini-Mental State Examination.ResultsThe scores for agitation were positively and robustly correlated with the scores for irritability in all stages of AD, and with the scores for anxiety in the moderate and severe stages. The scores for agitation were also correlated with those for sleep disorders in severe AD stage or disinhibition in the moderate AD stage. Multiple regression analysis identified irritability influencing the agitation in moderate and severe stages, and sleep disorders influencing the agitation in the severe stage.ConclusionsAs comorbid NPSs with agitation, characteristic affective, impulsive, and circadian abnormalities may be relevant to generate diverse subsyndromes in AD. Irritability consistently causes agitated behaviors, including refusal to take one's own care, and diurnal rhythm disorder in the severe AD stage may also cause poor acceptance for self-care.