OPPOSING EFFECTS OF DHEA REPLACEMENT IN ELDERLY SUBJECTS ON DECLARATIVE MEMORY AND ATTENTION AFTER EXPOSURE TO A LABORATORY STRESSOR

Aging is accompanied by a continuous decline of the adrenal steroid ho rmone DHEA and its ester DHEAS. Results from studies in rodents have d emonstrated that DHEA(S) administration can enhance memory in several test paradigms. However studies from this laboratory did not find posi tive effects of DHEA treatment on cognitive performance in young and e lderly humans. With respect to a possible mechanism of DHEA activity, effects on several neurotransmitter receptors as well as a possible an tiglucocorticoid action are discussed. For high levels of glucocortico ids, a disruptive effect on hippocampal mediated memory is documented in rodents and humans. Therefore it was speculated that, if an antiglu cocorticoid action of DHEA would underlie the observed beneficial effe cts of DHEA on memory, these effects might only be detectable if subje cts are stressed land therefore have high cortisol levels). To lest th is hypothesis 75 elderly women and men participated in a placebo contr olled experiment. Subjects took DHEA (50 mg/day) or placebo for 2 week s (double blind). Thereafter they participated in a standardized psych osocial laboratory stressor (Trier Social Stress Test; TSST). Before a nd after stress exposure subjects completed two declarative memory tes ts (visual-verbal and spatial) as well as one attention test. In addit ion recall of visual material learned before stress was assessed after stress. Baseline DHEAS levels were significantly lower compared with young adults. DHEA replacement increased DHEAS levels into ranges foun d in young subjects. DHEA-substituted subjects showed a trend towards a larger cortisol stress response. In the visual memory test subjects under DHEA recalled less items after stress which they had learned bef ore stress. In the attention test however subjects under DHEA performe d better than subjects from the placebo group after stress. No interac tion between stress and DHEA was found for the spatial memory task. Th e effects of DHEA substitution on memory and attention after stress ex posure seem to be heterogenous. While recall of previously learned mat erial seems to be impaired, attention is enhanced. These results do no t support the idea of a direct antiglucocorticoid or anti-stress effec t of DHEA on hippocampal mediated memory functions. (C) 1998 Elsevier Science Ltd. All rights reserved.