Growth hormone response to clonidine predicts aggression in Alzheimer’s disease

Abstract

Objective: The neurobiology of aggression in Alzheimer’s Disease (AD) remains unknown. The objective of this study was to determine if altered central noradrenergic (NE) responsiveness is related to aggression in AD. Methods: Fifteen institutionalized, non-depressed elderly (11 males, four females, mean age 81.5±5.5) with probable AD, severe cognitive impairment (MMSE mean 3.3±4.6) and significant behavioral disturbances (Neuropsychiatric Inventory (NPI) score≥8) were studied. Growth Hormone (GH) response to clonidine challenge (5 μg/kg) was used as an index of central α 2-adrenergic function. Results: When patients were divided into those with preserved GH response (GH maximum change from baseline>0, n=6) and those with blunted GH response (GH maximum change from baseline≤0, n=9) there were significant differences in levels of aggression as measured by the Cohen-Mansfield Agitation Inventory (CAMI) physical aggression subscale ( p=.026). Patients with blunted GH response also had significantly higher levels of aggression against others on the retrospective Overt Aggression Scale ( p=0.027). Conclusions: Certain types of physically aggressive behaviors are associated with a blunted GH response to clonidine challenge. This finding is consistent with compensatory down-regulation of post-synaptic α 2-adrenergic receptors in response to enhanced NE outflow in aggressive AD patients.