Effects of dehydroepiandrosterone replacement in elderly men on event-related potentials, memory, and well-being

Background, In humans, concentrations of the adrenal steroid hormone dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) decline with age. Results from studies in rodents have suggested that DHEA administration can improve memory performance as well as neuronal plasticity. However, a first study from our laboratory could not demonstrate beneficial effects of DHEA substitution on cognitive performance and well-being in elderly subjects. To further evaluate whether DHEA replacement has effects on the central nervous system, an experiment using event-related potentials (ERPs) was conducted. Methods, In this placebo-controlled crossover study, 17 elderly men (mean age, 71.1 +/- 1.7 yr; range 59-81 yr) took placebo or DHEA (50 mg/day) for 2 weeks (double blind). After each treatment period subjects participated in an auditory oddball paradigm with three oddball blocks. In the first two blocks subjects had to count the rare tone silently, whereas, in the third block they had to press a button. In addition, memory tests assessing visual, spatial, and semantic memory as well as questionnaires on psychological and physical well-being were presented. Results. Baseline DHEAS levels were lower compared with young adults. After 2-week DHEA replacement, DHEAS levels rose 5-fold to levels observed in young men. DHEA substitution modulated the P3 component of the ERPs, which reflects information updating iii short-term memory. P3 amplitude was increased after DHEA administration, and only selectively in the second oddball block. DHEA did not influence P3 latency. Moreover, DHEA did not enhance memory or mood. Conclusions. A 2-week DHEA replacement in elderly men results in changes in electrophysiological indices of central nervous system stimulus processing if the task is performed repeatedly. However, these effects do not appear to be strong enough to improve memory or mood.