Elevated cortisol levels in Cushing's disease are associated with cognitive decrements

Objective: The objective of this study was to use Cushing's disease as a un ique human model to elucidate the cognitive deficits resulting from exposur e to chronic stress-level elevations of endogenous cortisol. Methods: Forty -eight patients with a first episode of acute, untreated Cushing's disease and 38 healthy control subjects were studied. Results: Scores for four of f ive verbal IQ subtests were significantly lower in patients with Cushing's disease; their scores were significantly lower for only one nonverbal perfo rmance IQ subtest (block design). Verbal, but not visual, learning and dela yed recall at 30 minutes were significantly decreased among patients with C ushing's disease. Although verbal delayed recall was significantly lower in these patients, the retention index (percentage), which compares the amoun t of initially learned material to that recalled after the delay, was not s ignificantly decreased. There was no significant association between depres sion scores and cognitive performance. A higher degree of cortisol elevatio n was associated with poorer performance on several subtests of learning, d elayed recall, and visual-spatial ability. Conclusions: Chronically elevate d levels of glucocorticoids have deleterious effects on particular domains of cognition. Verbal learning and other verbal functions seem more vulnerab le than nonverbal functions. The results suggest that both the neocortex an d hippocampus are affected.