DHEA treatment of Alzheimer's disease: A randomized, double-blind, placebo-controlled study
ABSTRACT To compare the efficacy and tolerability of dehydroepiandrosterone (DHEA) vs placebo in AD.
Fifty-eight subjects with AD were randomized to 6 month's treatment with DHEA (50 mg per os twice a day; n = 28) or placebo (n = 30) in a multi-site, double-blind pilot trial. Primary efficacy measures assessed cognitive functioning (the AD Assessment Scale-Cognitive [ADAS-Cog]) and observer-based ratings of overall changes in severity (the Clinician's Interview-Based Impression of Change with Caregiver Input [CIBIC-Plus]). At baseline, 3 months, and 6 months, the ADAS-Cog was administered, and at 3 and 6 months, the CIBIC-Plus was administered. The 6-month time point was the primary endpoint.
Nineteen DHEA-treated subjects and 14 placebo-treated subjects completed the trial. DHEA was relatively well-tolerated. DHEA treatment, relative to placebo, was not associated with improvement in ADAS-Cog scores at month 6 (last observation carried forward; p = 0.10); transient improvement was noted at month 3 (p = 0.014; cutoff for Bonferroni significance = 0.0125). No difference between treatments was seen on the CIBIC-Plus at either the 6-month or the 3-month time points.
DHEA did not significantly improve cognitive performance or overall ratings of change in severity in this small-scale pilot study. A transient effect on cognitive performance may have been seen at month 3, but narrowly missed significance.
Full-textDOI: · Available from: Eugene -- Roberts, May 14, 2015
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- "No studies of DHEA replacement on healthy elderly populations, either acute administration or chronic (up to 12 months) supplementation, have shown a benefit in memory with treatment (Wolf et al. 1997, 1998; Wolf and Kirschbaum 1999; Arlt et al. 2001; Grimley Evans et al. 2006; Kritz- Silverstein et al. 2008), and some have even observed a negative effect on memory (Wolf et al. 1998; Parsons et al. 2006). DHEA supplementation has also shown no benefit in the treatment of Alzheimer's disease (Wolkowitz et al. 2003). "
ABSTRACT: 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.Age 09/2009; 32(1):61-7. DOI:10.1007/s11357-009-9113-4 · 3.45 Impact Factor
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- "Secondly, the use of such high doses of DHEA as used here over the long term, could theoretically lead, via metabolism into active sex steroids, to adverse Alhaj et al. DHEA, episodic memory, cortisol and mood 23/42 effects, such as enhanced hormone-sensitive tumour growth (Wolkowitz et al. 2003). "
ABSTRACT: Dehydroepiandrosterone (DHEA) has been reported to enhance cognition in rodents, although there are inconsistent findings in humans. The aim of this study was to investigate the effects of DHEA administration in healthy young men on episodic memory and its neural correlates utilising an event-related potential (ERP) technique. Twenty-four healthy young men were treated with a 7-day course of oral DHEA (150 mg b.d.) or placebo in a double blind, random, crossover and balanced order design. Subjective mood and memory were measured using visual analogue scales (VASs). Cortisol concentrations were measured in saliva samples. ERPs were recorded during retrieval in an episodic memory test. Low-resolution brain electromagnetic tomography (LORETA) was used to identify brain regions involved in the cognitive task. DHEA administration led to a reduction in evening cortisol concentrations and improved VAS mood and memory. Recollection accuracy in the episodic memory test was significantly improved following DHEA administration. LORETA revealed significant hippocampal activation associated with successful episodic memory retrieval following placebo. DHEA modified ERPs associated with retrieval and led to a trend towards an early differential activation of the anterior cingulate cortex (ACC). DHEA treatment improved memory recollection and mood and decreased trough cortisol levels. The effect of DHEA appears to be via neuronal recruitment of the steroid sensitive ACC that may be involved in pre-hippocampal memory processing. These findings are distinctive, being the first to show such beneficial effects of DHEA on memory in healthy young men.Psychopharmacology 12/2006; 188(4):541-51. DOI:10.1007/s00213-005-0136-y · 3.99 Impact Factor
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- "suggestion that supplementation with DHEAS may serve a preventive role in ameliorating the adverse symptoms of aging, disease, and stress. DHEAS administration , therefore, has been evaluated as a potential therapeutic agent in the treatment of a broad range of maladies, including AIDS (Clerici et al., 1997; Araghi-Niknam et al., 1998), Alzheimer's disease (Wolkowitz et al., 2003), and depression (Reus et al., 1997; van Broekhoven and Verkes, 2003). For these reasons, there is a large market for DHEAS, which is sold without a prescription as a dietary supplement. "
ABSTRACT: Dehydroepiandrosterone sulfate (DHEAS) is a steroid hornone that is synthesized, de novo, in the brain. Endogenous DHEAS levels correlate with the quality of mental and physical health, where the highest levels of DHEAS occur in healthy young adults and reduced levels of DHEAS are found with advanced age, disease, or extreme stress. DHEAS supplementation, therefore, may serve as a therapeutic agent against a broad range of maladies. This paper summarizes laboratory findings on dose-response relationships between DHEAS and cognitive and electrophysiological measures of hippocampal functioning. It was found that a low, but not a high, dose of DHEAS enhanced hippocampal primed burst potentiation (a physiological model of memory) as well as spatial (hippocampal-dependent) memory in rats. This complex dose-response function of DHEAS effects on the brain and memory may contribute toward the inconsistent findings that have been obtained by other investigators in studies on DHEAS administration in people.Nonlinearity in Biology Toxicology and Medicine 11/2004; 2(4):371-7. DOI:10.1080/15401420490900290