Glucocorticoids decrease brain volume and negatively impact cognition: BMJ

The use of both systemic and inhaled glucocorticoids is related with diminished white matter integrity and modest alterations in grey matter volume (GMV), says an article published in British Medical Journal.

Glucocorticoids are among the most often prescribed medications on the market due to their immunosuppressive effects, with an estimated yearly incidence of systemic glucocorticoid usage ranging between 0.5% and 3%. Glucocorticoids, both systemic and local (particularly inhaled), are linked with a variety of potentially significant metabolic, cardiovascular, and musculoskeletal adverse effects. Merel van der Meulen and colleagues carried out this study to check if glucocorticoid use would be associated with reduced grey matter volumes in the limbic system and hippocampus, a widespread decrease in fractional anisotropy (FA) and increase in mean diffusivity (MD) throughout the brain, and worse cognitive and emotional outcomes.

This was a cross-sectional, prospective population-based cohort study of persons recruited between 2006 and 2010 in the United Kingdom. Following removal for neurological, psychiatric, or endocrinological history, as well as the use of psychotropic medication, 222 systemic glucocorticoid users, 557 inhaled glucocorticoid users, and 24,106 controls with available T1 and diffusion MRI data were included. Differences in 22 volumetric and 14 diffusion MRI parameters between glucocorticoid users and controls were identified using linear regression models adjusted for possible variables. Cognitive performance (six tests) and emotional symptoms were secondary outcomes (four questions).

The key findings of this study were:

1. Systemic and inhaled glucocorticoid usage were both linked with decreased white matter integrity (lower FA and greater mean diffusivity) compared to controls, with systemic users having larger effect sizes than inhaled users.

2. Inhaled users showed lower amygdala GMV than controls, but systemic users had higher caudate GMV.

3. In terms of secondary outcomes, when compared to controls, systemic users performed worse on the symbol digit replacement test and reported greater depressed symptoms, indifference, tenseness/restlessness, and tiredness/lethargy.

4. Users who inhaled just reported increased tiredness/lethargy.

In conclusion, this study found that both systemic and inhaled glucocorticoids are linked with an apparently broad decrease in white matter integrity, which might explain some of the neuropsychiatric adverse effects seen in glucocorticoid users. Because these drugs are frequently used, medical specialists must be aware of these correlations, and study into alternate treatment alternatives is essential.

Reference: 

van der Meulen, M., Amaya, J. M., Dekkers, O. M., & Meijer, O. C. (2022). Association between use of systemic and inhaled glucocorticoids and changes in brain volume and white matter microstructure: a cross-sectional study using data from the UK Biobank. In BMJ Open (Vol. 12, Issue 8, p. e062446). BMJ. https://doi.org/10.1136/bmjopen-2022-062446