DHEA treatment of Alzheimer's disease: A randomized, double-blind, placebo-controlled study

Department of Psychiatry, Center for Neurobiology and Psychiatry, University of California San Francisco (UCSF) School of Medicine, USA.
Neurology (Impact Factor: 8.3). 05/2003; 60(7):1071-6. DOI: 10.1212/01.WNL.0000052994.54660.58
Source: PubMed

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.

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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). "
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    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). "
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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. "
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    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.
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