Stimulation of the mineralocorticoid receptor improves memory in young and elderly healthy individuals

Glucocorticoids play an important role in cognitive function and act on glucocorticoid receptors and mineralocorticoid receptors (MRs) in the brain. Previously, the blockade of the MR has been shown to impair visuospatial and working memory in healthy young men. Here, we investigated the effects of the MR agonist fludrocortisone on memory in young and elderly healthy individuals. Thirty-one young (mean age 25.4 ± 4.6 years) and 22 elderly (mean age 63.2 ± 8.2 years) healthy participants received the MR agonist fludrocortisone (0.4 mg) or placebo at least 3 days apart in a randomized, double-blind within-subject cross-over design. We measured verbal memory (auditory verbal learning test), nonverbal memory (Rey/Taylor complex figure test), and working memory (digit-span task). As expected, young participants performed significantly better than elderly individuals in visuospatial memory (effect of group: F = 42.7, p < 0.01), verbal memory (F = 33.1, p < 0.01), and working memory (digit-span backward: F = 4.5, p = 0.04). For visuospatial memory (F = 5.0, p = 0.03) and short-term and working memory (digit-span forward: F = 4.2, p = 0.05), we found a significant treatment effect indicating better memory performance after fludrocortisone compared with placebo across groups. In concert with the previous studies, our data suggest a role of the MR in memory function. A cognitive enhancing effect by MR stimulation warrants future studies.