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Only a few studies have objectively compared cognitive function as the primary outcome between patients with ACI and controls, and these efforts have yielded inconsistent results. In this review, we examine the challenges facing researchers studying cognitive function in adult patients with ACI. We consider the effect of dysregulated cortisol on cognition in patients with ACI, and the inability of current guideline-recommended glucocorticoid (GC) treatment regimens to accurately reproduce circadian and ultradian cortisol secretion rhythms. Factors that contribute to inter- and intra-individual response to GC are presented; the indirect effects of ACI comorbidities, complications, and symptoms on cognitive dysfunction are reviewed; and obstacles to employing neurocognitive testing are identified. Finally, we outline potential approaches to studying cognition in ACI using well-designed studies that account for the complexities and gaps in ACI research.<\/jats:p>","DOI":"10.1210\/endrev\/bnaf029","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T11:48:12Z","timestamp":1756813692000},"page":"24-51","source":"Crossref","is-referenced-by-count":1,"title":["Cognitive Assessment in Adults With Adrenal Cortisol Insufficiency: Challenges and Opportunities"],"prefix":"10.1210","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2912-5355","authenticated-orcid":false,"given":"Anat","family":"Ben-Shlomo","sequence":"first","affiliation":[{"name":"Department of Medicine, Multidisciplinary Adrenal Program, Pituitary Center, Cedars-Sinai Medical Center , Los Angeles, CA 90048 ,","place":["USA"]},{"name":"Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center , Los Angeles, CA 90048 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