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Enhanced adrenal sensitivity to adrenocorticotrophic hormone (ACTH) is evidence of HPA axis hyperactivity in Alzheimer's disease

Published online by Cambridge University Press:  09 July 2009

J. T. O'Brien*
Affiliation:
Department of Psychiatry and Department of Diabetes and Endocrinology, University of Melbourne, Royal Melbourne Hospital, Melbourne, VIC, Australia
D. Ames
Affiliation:
Department of Psychiatry and Department of Diabetes and Endocrinology, University of Melbourne, Royal Melbourne Hospital, Melbourne, VIC, Australia
I. Schweitzer
Affiliation:
Department of Psychiatry and Department of Diabetes and Endocrinology, University of Melbourne, Royal Melbourne Hospital, Melbourne, VIC, Australia
M. Mastwyk
Affiliation:
Department of Psychiatry and Department of Diabetes and Endocrinology, University of Melbourne, Royal Melbourne Hospital, Melbourne, VIC, Australia
P. Colman
Affiliation:
Department of Psychiatry and Department of Diabetes and Endocrinology, University of Melbourne, Royal Melbourne Hospital, Melbourne, VIC, Australia
*
1Address for correspondence: Dr John T. O'Brien, Brighton Clinic, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE.

Synopsis

Adrenal sensitivity was assessed in 16 non-depressed patients with NINCDS/ADRDA Alzheimer's disease (AD) and 18 control subjects by measuring cortisol response to low dose (0·05 μg/kg i.v.) exogenous adrenocorticotrophic hormone (ACTH). Controlling for sex and medication, both peak cortisol level (peak–baseline) and area under cortisol response curve (AUC above baseline) were significantly greater in AD subjects. This shows that HPA axis hyperactivity, as demonstrated by enhanced adrenal sensitivity to ACTH, occurs in AD. Similar findings have been reported to occur in depression. Among AD subjects, AUC cortisol response correlated with current age (r = 0·70, P = 0·001) and age at onset of dementia (r = 0·73, P = 0·001) and an inverse correlation was seen between cortisol AUC and cognitive test (CAMCOG) score (r = −0·51, P = 0·044). Our findings suggest that HPA axis hyperactivity in AD is associated with advancing age and cognitive dysfunction. Such changes may be cause, or consequence, of neuronal loss.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 1996

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References

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