The function of the hypothalamic-pituitary-adrenal axis in Alzheimer's disease. Response to insulin hypoglycaemia.
BACKGROUND
To investigate an association between HPA axis dysfunction, depression and cognitive impairment, we assessed subjects with mild Alzheimer's disease (AD).


METHODS
Sixteen non-depressed subjects with AD according to NINCDS/ADRDA criteria and 18 normal controls underwent the insulin hypoglycaemia (IH) test and the dexamethasone suppression test (DST).


RESULTS
The AD subjects showed a blunted response of adrenocorticotrophic hormone (ACTH) to IH compared with controls (P = 0.019). ACTH response (area under curve) correlated with a score for cognitive ability (CAMCOG) (r = 0.64, P < 0.01). AD subjects had a shorter time to peak cortisol level than controls (P = 0.004), although total cortisol response was normal.


CONCLUSIONS
The AD subjects show evidence of adrenal hyper-responsiveness and normal immediate (rate-sensitive) glucocorticoid feedback. An association between HPA axis dysfunction and organic brain pathology in AD subjects may be mediated by cell loss in the hippocampus.
O'Brien
J T
JT
University of Melbourne Department of Psychiatry, Australia.
Schweitzer
I
I
Ames
D
D
Mastwyk
M
M
Colman
P
P
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000503:physiopathology* / Q000523:psychology; D003907:Dexamethasone; D003937:Diagnosis, Differential; D005246:Feedback / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007328:Insulin; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010913:Pituitary-Adrenal System / Q000503:physiopathology*
D007328:Insulin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone