Brain structure in autoimmune Addison's disease

Abstract

Long-term disturbances in cortisol levels might affect brain structure in individuals with autoimmune Addison's disease (AAD). This study investigated gray and white matter brain structure in a cohort of young adults with AAD. T1- and diffusion-weighted images were acquired for 52 individuals with AAD and 70 healthy controls, aged 19-43 years, using magnetic resonance imaging. Groups were compared on cortical thickness, surface area, cortical gray matter volume, subcortical volume (FreeSurfer), and white matter microstructure (FSL tract-based spatial statistics). Individuals with AAD had 4.3% smaller total brain volume. Correcting for head size, we did not find any regional structural differences, apart from reduced volume of the right superior parietal cortex in males with AAD. Within the patient group, a higher glucocorticoid (GC) replacement dose was associated with smaller total brain volume and smaller volume of the left lingual gyrus, left rostral anterior cingulate cortex, and right supramarginal gyrus. With the exception of smaller total brain volume and potential sensitivity of the parietal cortex to GC disturbances in men, brain structure seems relatively unaffected in young adults with AAD. However, the association between GC replacement dose and reduced brain volume may be reason for concern and requires follow-up study.

Keywords: Addison; brain structure; cortisol; executive function; working memory.

Fig. 1

Reduced volume of the right superior parietal cortex in males with AAD. Male participants with AAD (n = 19) had reduced volume of the right superior parietal cortex compared to control males (n = 31), t(max) = 2.72, size = 1166.51 mm², peak Talairach (X = 30.6, Y = −47.5, Z = 44.4), as assessed with vertex-wise analysis in FreeSurfer. The color bar indicates t-values, with red indicating positive t-values, i.e. increased volume in controls.

Fig. 2

Associations between brain structure and visuospatial working memory. There was a significant interaction between group (patient or control) and volume of the left posterior cingulate cortex (PCC), and performance on a visuospatial working memory test (Span Board forward) (B = −0.003, 1 = 0.014). Post hoc tests revealed that in individuals with AAD, those with larger volume of the left PCC performed worse on the task (B = −0.003, P = 0.016), while in healthy controls, those with larger volumes performed better (B = 0.001, P = 0.048).

Fig. 3

Associations between GC medication dose in mg/m²/day and brain volumes. A higher GC replacement dose in mg/m2/day was associated with reduced volume of the (A) left lingual (B = −106.28, q = 0.045), (B) rostral anterior cingulate (ACC) (B = −59.45, q = 0.033), and (C) right supramarginal gyrus (B = −177.30, q = 0.045), but not when correcting for intracranial volume (ICV). D) GC replacement dose in mg/m²/day was associated with reduced total brain volume (B = −8383, P = 0.027), even when correcting for height (B = −7124, P = 0.45).