The effects of synthetic glucocorticoid treatment for inflammatory disease on brain structure, function, and dementia outcomes: A systematic review

• Published in: Brain research 2023-01, Vol.1798, p.148157, Article 148157
• Main Authors: Shorey, Carrie L., Mulla, Reem T., Mielke, John G.
• Format: Article
• Language: English
• Subjects: Alzheimer Disease; Alzheimer's disease; Amygdala; Atrophy - drug therapy; Atrophy - pathology; Brain; Cognitive Dysfunction - chemically induced; Cognitive Dysfunction - complications; Cognitive Dysfunction - drug therapy; Cognitive function; Dementia; Glucocorticoid; Glucocorticoids; Hippocampus; Humans
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2022.148157

[Display omitted] •Long-term glucocorticoid usage was associated with significant atrophy in the hippocampus and amygdala.•Executive function, particularly working memory, was also significantly poorer with long-term glucocorticoid use.•Changes in episodic memory were not associated with long-term usage.•The null to negative association of long-term usage with most dementia types and Alzheimer’s disease suggests a protective effect. Many regions of the brain have a high density of glucocorticoid receptors, and the prolonged elevation of endogenous glucocorticoids may cause neurotoxicity and increase risk for cognitive decline and dementia. However, despite synthetic glucocorticoids being the first line of treatment for many inflammatory diseases, few studies have addressed whether therapeutic glucocorticoids may have similar undesirable effects on the brain. Thus, our systematic review investigated the impact of long-term glucocorticoid usage on adult brain structure, cognitive function, and dementia risk. We identified 13 studies that met our eligibility criteria and found conflicting results dependent on the outcome studied. In particular, all but one study on hippocampal and amygdalar volumes found significant atrophy of both structures occurred in those who took glucocorticoids. Additionally, executive function, particularly working memory, and global cognitive function were significantly poorer in those taking long-term glucocorticoids. Notably, declines in episodic memory were not associated with long-term usage. Furthermore, most studies of dementia (all-cause) and Alzheimer’s disease, excluding vascular dementia, showed null to negative associations with glucocorticoids, suggesting a potential protective effect. Therefore, glucocorticoid therapy in those with inflammatory disease may impair certain brain structures and specific cognitive functions, but could lead to a significantly reduced risk of dementia.