Dehydroepiandrosterone and age-related cognitive decline
- 190 Downloads
In humans the circulating concentrations of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) decrease markedly during aging, and have been implicated in age-associated cognitive decline. This has led to the hypothesis that DHEA supplementation during aging may improve memory. In rodents, a cognitive anti-aging effect of DHEA and DHEAS has been observed but it is unclear whether this effect is mediated indirectly through conversion of these steroids to estradiol. Moreover, despite the demonstration of correlations between endogenous DHEA concentrations and cognitive ability in certain human patient populations, such correlations have yet to be convincingly demonstrated during normal human aging. This review highlights important differences between rodents and primates in terms of their circulating DHEA and DHEAS concentrations, and suggests that age-related changes within the human DHEA metabolic pathway may contribute to the relative inefficacy of DHEA replacement therapies in humans. The review also highlights the value of using nonhuman primates as a pragmatic animal model for testing the therapeutic potential of DHEA for age-associate cognitive decline in humans.
KeywordsDehydroepiandrosterone Cognitive decline Intracrinology Neurosteroidogenesis
This work was supported by National Institute of Health grants: AG-019914, AG-026472, AG-029612 HD-29186, and RR-00163.
- Abbott DH, Bird IM (2008) Nonhuman primates as models for human adrenal androgen production: function and dysfunction Rev Endocr Metab Disord doi: 10.1007/s11154-008-9099-8
- Bohacek J, Bearl AM, Daniel JM (2008) Long-term ovarian hormone deprivation alters the ability of sebsewuent oestradiol replacement to regulate choline acetyltransferase protein levels in the hippocampus and prefrontal cortex of middle-aged rats. J Neuroendocrinol 20:1023–1027CrossRefPubMedGoogle Scholar
- Grimley Evans J, Malouf R, Huppert F et al. (2006) Dehydroepiandrosterone (DHEA) supplementation for cognitive function in healthy elderly people. Cochrane Database of Syst Rev CD006221Google Scholar
- Lethaby A, Hovervorst E, Richards M et al. (2008) Hormone replacement therapy for cognitive function in postmenopausal women. Chochrane Database of Syst Rev CD003122Google Scholar
- Nguyen AD, Conley AJ (2008) Adrenal androgens in humans and nonhuman primates: production, zonation and regulation. In: Flück CE, Miller WL (eds) Disorders of the human adrenal cortex. Endocr Dev Karger Basel 13:33–54Google Scholar