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The limbic-hypothalamic-pituitary-adrenal axis in Alzheimer's disease
Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
1994 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Dysfunction of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis is a common finding in advanced dementia. In this study, the function of the LHPA axis at different levels was investigated in patients with dementia and in healthy elderly.

A subtle disturbance in the feedback regulation of the LHPA axis was found in patients with early (i.e., mild to moderate) Alzheimer’s disease (AD). After 0.5 mg dexamethasone, serum cortisol levels were less suppressed in AD patients and plasma adrenocorticotropin (ACTH) levels were lower as compared with healthy elderly. After stimulation with human corticotropin-releasing hormone a blunted ACTH response was found in AD patients while relative serum cortisol, dehydroepiandrosterone, and androstenedione responses were increased. Significant correlations were found between low plasma ACTH levels and temporal lobe atrophy and between low peak plasma ACTH levels and hippocampal atrophy measured with computer tomography. Patients with advanced AD and multi-infarct dementia had lower basal levels of dehydroepiandrosterone sulphate in combination with no difference in cortisol levels, resulting in a high cortisol/DHAS ratio. The difference persisted after adjustments for age and sex in a multivariate analysis. In patients with early AD, basal serum levels of dehydroepiandrosterone and androstenedione were increased, and this increase was accentuated after stimulation with ACTH. Peripheral glucocorticoid sensitivity was examined by skin vasoconstrictor blanching tests. Patients with AD and patients treated with glucocorticoids showed skin blanching at higher clobetasol concentrations than healthy elderly.

These findings justify further investigations on the role of LHPA axis dysfunction in Alzheimer’s disease and its possible importance for the pathophysiology of the disease.

Place, publisher, year, edition, pages
Umeå: Umeå universitet , 1994. , p. 69
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 408
Keyword [en]
Alzheimer’s disease, multi-infarct dementia, hippocampus, temporal lobe, adrenal androgens, adrenocorticotropin, corticotropinreleasing hormone, cortisol, skin blanching
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:umu:diva-140822OAI: oai:DiVA.org:umu-140822DiVA, id: diva2:1150634
Projects
digitalisering@umu
Available from: 2017-10-19 Created: 2017-10-19 Last updated: 2017-11-07Bibliographically approved

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CiteExportLink to record
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Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
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More styles
Language
  • de-DE
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  • Other locale
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Output format
  • html
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