Growth hormone response to clonidine predicts aggression in Alzheimer's disease.
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 > or = 8) were studied. Growth Hormone (GH) response to clonidine challenge (5 microg/kg) was used as an index of central alpha(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 < or = 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 alpha(2)-adrenergic receptors in response to enhanced NE outflow in aggressive AD patients.
Herrmann
Nathan
N
Department of Psychiatry, Sunnybrook and Women's College Health Sciences Centre, Room FG05, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5. nathan.herrmann@sw.ca
Lanctôt
Krista L
KL
Eryavec
Goran
G
Van Reekum
Robert
R
Khan
Lyla R
LR
D000316:Adrenergic alpha-Agonists; D000368:Aged; D000369:Aged, 80 and over; D000374:Aggression; D000544:Alzheimer Disease / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D001526:Behavioral Symptoms / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine; D005260:Female; D019382:Human Growth Hormone / Q000097:blood* / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism; D011237:Predictive Value of Tests; D013268:Stimulation, Chemical
D000316:Adrenergic alpha-Agonists; D019382:Human Growth Hormone; D003000:Clonidine; D009638:Norepinephrine