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Dementia: a neuroendocrine perspective.

A Polleri¹, M V Gianelli, G Murialdo

¹Department of Endocrinological and Metabolic Sciences, University of Genoa, Italy.

Journal of Endocrinological Investigation

|March 9, 2002

Summary

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Alzheimer's disease (AD) involves complex factors, including stress hormones. Reduced DHEAS and increased glucocorticoids may worsen brain dysfunction in AD.

Area of Science:

Neuroendocrinology
Neurophysiology
Gerontology

Background:

The exact causes of Alzheimer's disease (AD) remain unclear, necessitating consideration of genetic, environmental, and neurophysiological factors.
Neuroendocrine system dysregulation, particularly involving the hypothalamic-pituitary-adrenal (HPA) axis, is implicated in AD pathogenesis.
Stress and elevated glucocorticoid levels can negatively impact neuronal survival, while dehydroepiandrosterone sulfate (DHEAS) may offer neuroprotection.

Purpose of the Study:

To review the neuroendocrine implications in Alzheimer's disease (AD).
To discuss the roles of stress hormones, glucocorticoids, and DHEAS in neuronal function and dysfunction within the context of aging and AD.
To explore the interplay between neuroendocrine factors and other mechanisms of neuronal damage in AD.

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Main Methods:

Review of experimental and clinical evidence.
Analysis of changes in hypothalamic-pituitary-adrenal axis function in AD.
Examination of the impact of glucocorticoids and DHEAS on hippocampal function and neuronal survival.

Main Results:

Glucocorticoid hypersecretion and decreased DHEAS levels are associated with hippocampal dysfunction in aging and AD.
Glucocorticoids and beta-amyloid contribute to neuronal damage, alongside excitatory amino acids, Ca++, and reactive oxygen species (ROS).
Neuroprotective effects of insulin-like growth factors (IGFs) are diminished in aging and AD, influenced by cortisol and DHEAS levels.

Conclusions:

Altered HPA axis function, characterized by high cortisol and low DHEAS, is a significant factor in AD.
The balance between glucocorticoids and DHEAS is critical for maintaining neuronal health and cognitive function.
Therapeutic strategies targeting the neuroendocrine system may offer potential benefits for managing AD.