Acute Modulation of Aged Human Memory by Pharmacological Manipulation of Glucocorticoids

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Abstract
In a previous longitudinal study of basal cortisol levels and cognitive function in humans, we showed that elderly humans with 4- to 7-yr cumulative exposure to high levels of cortisol present memory impairments, compared with elderly humans with moderate cortisol levels over years. Here, we measured whether memory performance in two groups of elderly hu- mans separated on the basis of their cortisol history over a 5-yr period could be modulated by a hormone-replacement protocol in which we inhibited cortisol secretion by the ad- ministration of metyrapone and then restored baseline cor- tisol levels by infusion of hydrocortisone. We showed that in elderly subjects with a 5-yr history of moderate cortisol levels (n 8), metyrapone treatment significantly impaired memory performance, a deficit that was reversed following hydrocor- tisone replacement. In the elderly subjects with a 5-yr history of high cortisol levels and current memory deficits (n 9), metyrapone treatment did not have any significant effect on memory performance, but hydrocortisone treatment signifi- cantly decreased delayed memory. These results suggest that memory function in elderly humans can be intensely modu- lated by pharmacological manipulation of glucocorticoids, al- though the direction of these effects depends on the cortisol history of each individual. (J Clin Endocrinol Metab 87: 3798 -3807, 2002)

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