Working memory performance and cognitive flexibility after dexamethasone or hydrocortisone administration in healthy volunteers

Several studies have shown that glucocorticoids can impair declarative memory retrieval and working memory (WM) performance. The aim of the present study was to investigate the impact of a high dose of hydrocortisone on WM, as well as to examine the effects of cortisol suppression via treatment with a high dose of dexamethasone (DEX). We hypothesized that hydrocortisone treatment results in an impaired cognitive function compared with placebo. We further expected that dexamethasone treatment is also followed by cognitive impairment, due to the hypothesis that very low levels of cortisol are also associated with alterations in memory performance. In a placebo-controlled study with a within-subject design, 16 healthy volunteers received placebo or 120 mg of hydrocortisone (two boluses of 60 mg) directly before neuropsychological testing or 4 mg of DEX the day before testing. We did not find any effect of hydrocortisone on WM and cognitive flexibility, even though cortisol levels were high at the time of testing. Furthermore, we did not find any effect of DEX treatment on WM and reaction time in a cognitive flexibility test. However, cognitive flexibility was negatively correlated with adrenocorticotropin (ACTH) in the DEX condition. Our results found no clear effect of hydrocortisone and dexamethasone treatment on WM. These results emphasize the need for further research on the association between hypothalamic-pituitary-adrenal axis activity and cognition. These studies should investigate the hypotheses of dose-dependent associations in more detail and should also include analyses on ACTH and cognition.