Cognitive dysfunction in patients with primary adrenal insufficiency: A systematic review.

Addison's disease (AD) entails a chronic insufficient production of gluco- and mineralocorticoids. Fatigue and decreased quality of life are frequently reported symptoms, but little is known about its effects on cognition. This study aims to explore the existence of cognitive impairment in patients with AD and the influence of treatment regimens. We conducted a systematic review. Inclusion criteria were met by 10 articles, most of them ranked as intermediate quality. Three studies analyzed the relationship between AD and cognitive impairment; one explored the effect of delaying treatment showing no effect on cognitive performance, and another one studied the effect of fludrocortisone treatment. Episodic memory was the most frequent cognitive domain impaired across studies, in comparison to healthy controls. Two papers investigated the relationship between impaired sleep quality and poor cognitive performance. Two studies related cognitive impairments with hypocortisolism-derived brain neuroglycopenia. Two studies investigated the effect of DHEA substitution. In conclusion, patients exhibit a moderately reduced performance in verbal learning. The pathophysiology of this impairment is likely multifactorial. Future studies should include larger sample sizes, the use of comprehensive and multi-domain neuropsychological and behavioral protocols, and neuroimaging.