Long-term cognitive effects of glucocorticoid excess in Cushing's syndrome

We previously found that patients with Cushing's syndrome (CS) scored lower than controls in several domains of cognitive function and that correction of hypercortisolism is not necessarily correlated with short-term improvement in intellectual performance. Here, we examined the long-term outcome in patients treated for CS by assessing the extent to which the detrimental effects of glucocorticoid (GC) excess on cognition can be reversed three years after corrective surgery.

A battery of neuropsychological tests, including tests of attention, visuospatial processing, learning and memory, and executive functioning were administered pre-treatment and 12, 24 and 36 months post-treatment.

We included 18 patients with endogenous CS recruited before surgical treatment and 18 controls matched for age, sex and education.

CS patients performed worse than controls on tests of attention, executive functioning and nonverbal aspects of memory. Moreover, at 36 months following eucortisolism, executive function performance and, to a lesser extent, attention tasks showed limited change compared to pre-treatment testing.

Chronic hypercortisolism is accompanied by a deleterious impact on aspects of cognitive function. This negative effect on attention, executive performance and nonverbal memory seen in patients with CS suggests a differential effect of excess GCs upon different brain areas and networks. This influence persists years after the return to normal cortisol secretion levels.