ESPE2016 Free Communications Adrenals (6 abstracts)
Identification of Novel Central Nervous System Imaging Biomarkers Associated with Cognitive Abnormalities in Patients with Congenital Adrenal Hyperplasia
Emma Webb a, , Lucy Elliott a , Dominic Carlin c , Martin Wilson c , Kirsty Hall d , Timothy Barrett b, , Vijay Salwani e , Wiebke Arlt a, , Nils Krone f , Andrew Peet b, & Amanda Wood d
aInstitute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; bBirmingham Children’s Hospital, Birmingham, UK; cInstitute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK; dInstitute of Psychology, University of Birmingham, Birmingham, UK; eUniversity Hospital Birmingham, Birmingham, UK; fUniversity of Sheffield, Sheffield, UK
Background: Management of patients with CAH remains challenging. There is increasing evidence to suggest that failure to optimize treatment during childhood not only affects final height but also leads to psychological and psychiatric problems. Previous qualitative structural T2-weighted MRI studies have identified white matter hyper-intensities in up to 46% of CAH patients. The nature and functional relevance of these abnormalities remains unknown.
Objective and hypotheses: We aimed to identify novel MRI brain biomarkers of CAH and to examine their association with cognitive abnormalities.
Method: All participants completed subtests of the Cambridge Neuropsychological Test Automated Battery and underwent brain volumetric, magnetic resonance spectroscopy and diffusion tensor imaging. Freesurfer (neural volumes and cortical thickness), TARQUIN (metabolites) and Tract Based Spatial Statistics (fractional anisotropy) were used to process the neuroimaging data. T-tests were performed to compare significance between groups, adjusted for multiple comparisons. Partial correlations were performed to assess the relationship between MRI markers and neuropsychological measures.
Results: Seventeen females with 21-hydroxylase deficiency and 18 age-matched healthy females were recruited (32.7 and 28.6 years, P=0.25). Patients with CAH had significantly lower episodic memory, learning and spatial working memory (P<0.001) scores. Patients with CAH had significant reductions in total brain volume (P=0.02), corpus callosum volume (P−0.03), hippocampal N-Acetyl Aspartate (P=0.03) and choline (P=0.002), brain fractional anisotropy (Figure A, P<0.01) and parahippocampal cortical thickness (B, left, C, right, P<0.05). There were significant relationships between; corpus callosum volume and spatial working memory (P=0.001), parahippocampal thickness, episodic and working memory (P<0.05), hippocampal choline and rapid visual information processing (P<0.02).
Conclusion: For the first time we have identified central nervous system imaging biomarkers of clinically significant cognitive abnormalities in patients with CAH. Further studies are required to determine the age of onset of these abnormalities and to develop preventative strategies.
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