Hostname: page-component-78c5997874-ndw9j Total loading time: 0 Render date: 2024-11-17T19:12:07.571Z Has data issue: false hasContentIssue false

The Function of the Hypothalamic–Pituitary–Adrenal Axis in Alzheimer's Disease

Response to Insulin Hypoglycaemia

Published online by Cambridge University Press:  02 January 2018

John T. O'Brien*
Affiliation:
University of Melbourne Department of Psychiatry
Isaac Schweitzer
Affiliation:
University of Melbourne Department of Psychiatry
David Ames
Affiliation:
University of Melbourne Department of Psychiatry
Maree Mastwyk
Affiliation:
University of Melbourne Department of Psychiatry
Peter Colman
Affiliation:
University of Melbourne Department of Endocrinology, University of Melbourne, Royal Melbourne Hospital, Australia
*
Dr John O'Brien, Hellesdon Hospital, Norwich NR6 5BE

Abstract

Background

To investigate an association between HPA axis dysfunction, depression and cognitive impairment, we assessed subjects with mild Alzheimer's disease (AD).

Method

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.

Type
Papers
Copyright
Copyright © Royal College of Psychiatrists, 1994 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders (3rd edn, revised) (DSM–III–R). Washington, DC: APA.Google Scholar
American Psychiatric Association Task Force (1987) The dexamethasone suppression test: an overview of its current status in psychiatry. American Journal of Psychiatry, 144, 12531262.CrossRefGoogle Scholar
Amsterdam, J. D., Maislin, G., Gold, P., et al (1989) The assessment of abnormalities in hormonal responsiveness at multiple levels of the hypothalamic-pituitary-adrenal axis in depressive illness. Psychoneuroendocrinology, 14, 4363.Google Scholar
Buckingham, J. C., Smith, T. & Loxley, H. D. (1992) The control of ACTH secretion. In The Adrenal Gland (ed. James, H. T.), pp. 131159. New York: Raven Press.Google Scholar
Carroll, B. J., Feinberg, M., Greden, J. F., et al (1981) A specific laboratory test for the diagnosis of melancholia. Archives of General Psychiatry, 38, 1522.Google Scholar
Checkley, S. (1992) Neuroendocrine mechanisms and the precipitation of depression by life events. British Journal of Psychiatry, 160 (suppl. 15), 717.Google Scholar
Dodt, C., Dittmann, J. H., Hruby, J., et al (1991) Different regulation of adrenocorticotrophin and cortisol secretion in young, mentally healthy elderly and patients with senile dementia of Alzheimer's type. Journal of Clinical Endocrinology and Metabolism, 72, 272276.Google Scholar
Ellis, M. J., Schmidli, R. S., Donald, R. A., et al (1990) Plasma corticotrophin-releasing factor and vasopressin responses to hypoglycaemia in normal man. Clinical Endocrinology, 32, 93100.CrossRefGoogle ScholarPubMed
Emery, V. O. & Oxman, T. E. (1992) Update on the dementia spectrum of depression. American Journal of Psychiatry, 149, 305317.Google Scholar
Estivariz, F. E., Lowry, P. J. & Jackson, S. (1992) Control of adrenal growth. In The Adrenal Gland (ed. James, V. H. T.), pp. 4371. New York: Raven Press.Google Scholar
Gold, P. W., Chrousos, G., Kellner, C., et al (1984) Psychiatric implications of basic and clinical studies with corticotropinreleasing factor. American Journal of Psychiatry, 141, 619627.Google ScholarPubMed
Greenwald, B. S., Mathe, A. A., Mohs, R. C., et al (1986) Cortisol and Alzheimer's disease, II: Dexamethasone suppression, dementia severity, and affective symptoms. American Journal of Psychiatry, 143, 442446.Google ScholarPubMed
Hamilton, M. (1960) A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry, 23, 5662.Google Scholar
Lesch, K. P., Ihl, R., Frolich, L. (1990) Endocrine responses to growth hormone releasing hormone and corticotropin releasing hormone in early-onset Alzheimer's disease. Psychiatry Research, 33, 107112.Google Scholar
Lopez, J. F., Kathol, R. G., Jaeckle, R. S., et al (1987) The HPA axis response to insulin hypoglycaemia in depression. Biological Psychiatry, 22, 153166.CrossRefGoogle ScholarPubMed
Maes, M., Claes, M., Vandewoude, M., et al (1992) Adrenocorticotropin hormone, β-endorphin and cortisol release to oCRH in melancholic patients. Psychological Medicine, 22, 317329.Google Scholar
Maguire, K. P., Tuckwell, V. M., Schweitzer, I., et al (1990) Dexamethasone kinetics in depressed patients before and after clinical response. Psychoneuroendocrinology, 15, 113123.Google Scholar
McKhann, G., Drachman, D., Folstein, M., et al (1984) Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of the Dept. of Health and Human Task Force in Alzheimer's Disease. Neurology, 34, 939944.CrossRefGoogle Scholar
Mitrakou, A., Ryan, C., Veneman, T., et al (1991) Hierarchy of glycaemic thresholds for counterregulatory hormone secretion, symptoms, and cerebral dysfunction. American Journal of Physiology, 260, E67E74.Google Scholar
O'Brien, J. T., Ames, D. & Schweitzer, I. (1993) HPA axis function in depression and dementia: a review. International Journal of Geriatric Psychiatry, 8, 887898.CrossRefGoogle Scholar
Poland, R. E., Rubin, R. T., Lesser, I. M., et al (1987) Neuroendocrine aspects of primary endogenous depression II. Serum dexamethasone concentrations and HPA cortical activity as determinants of the dexamethasone suppression test response. Archives of General Psychiatry, 44, 790795.Google Scholar
Roth, M., Tym, E., Mountjoy, C., et al (1986) CAMDEX: a standardised instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia. British Journal of Psychiatry, 149, 698709.Google Scholar
Sapolsky, R. M., Krey, L. C. & McEwen, B. (1986) The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocrine Reviews, 7, 284301.Google Scholar
Sapolsky, R. M., & Plotsky, P. M. (1990) Hypercortisolism and its possible neural bases. Biological Psychiatry, 27, 937952.Google Scholar
Tiller, J. W. G., Maguire, K. P., Schweitzer, I., et al (1988) The dexamethasone suppression test: a study in a normal population. Psychoneuroendocrinology, 13, 377384.Google Scholar
Weiner, M. F., Vobach, S., Svetlik, D., et al (1993) Cortisol secretion and Alzheimer's disease progression – a preliminary report. Biological Psychiatry, 34, 158163.CrossRefGoogle ScholarPubMed
Submit a response

eLetters

No eLetters have been published for this article.