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The limbic-hypothalamic-pituitary-adrenal axis in Alzheimer's disease
Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
1994 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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.

sted, utgiver, år, opplag, sider
Umeå: Umeå universitet , 1994. , s. 69
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 408
Emneord [en]
Alzheimer’s disease, multi-infarct dementia, hippocampus, temporal lobe, adrenal androgens, adrenocorticotropin, corticotropinreleasing hormone, cortisol, skin blanching
HSV kategori
Identifikatorer
URN: urn:nbn:se:umu:diva-140822OAI: oai:DiVA.org:umu-140822DiVA, id: diva2:1150634
Prosjekter
digitalisering@umuTilgjengelig fra: 2017-10-19 Laget: 2017-10-19 Sist oppdatert: 2017-11-07bibliografisk kontrollert

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