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The hypothalamic-pituitary-adrenal (HPA) system function in patients with Alzheimer's disease and the therapeutic implications


The role of hypothalamic-pituitary-adrenal (HPA) axis have been the subject of substantial studies in conditions such as major depression, posttraumatic stress disorder, and Cushing's syndrome. HPA disturbances have been associated with memory impairments and hypercortisolemia with atrophy of hippocampus, a limbic structure strong associated with memory and which function is pivotal for the regulation of the HPA system. The neropathologic hallmarks of Alzheimer disease are very prominent in the hippocampus. Recent discoveries support the existence of a more complicated relationship between stimulation of brain glucorticoid receptors and memory performance.

Materials and methods

A meta-analysis was conducted out of the 25 studies identified for this study's needs. The oldest was a study by Raskind et al (1982) and the newest a study by Csernansky et al (2006).


A number of valid tests (DST, CSF cortisol levels, UFC levels and Basal Cortisol Levels) have demonstrated an increased HPA activity in AD patients. Hippocampal atrophy was found to be closely associated with increased HPA activity. Hypercortisolemia, in the elderly have shown substantial memory deficits interconnected to a pattern of increasing cortisol levels.


Hyperactivity oh the HPA axis in AD leads to memory deficits. More studies of HPA function in normal aging persons, those with mild cognitive impairment and patients with Alzheimer disease, examining pertinent variables such as APOE e4 status, are needed to clarify these new findings. The antiglucorticoid agents seem to be a promising and effective tool in the treatment of particular conditions such as Alzheimer disease and Mild Cognitive Impairment.


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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Fitsioris, X., Theofanidis, D., Koutlas, E. et al. The hypothalamic-pituitary-adrenal (HPA) system function in patients with Alzheimer's disease and the therapeutic implications. Ann Gen Psychiatry 7 (Suppl 1), S242 (2008).

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