Abstract: SUN 433

Decreased prefrontal functional brain response in women with Cushing’s syndrome in remission

Presenter:


Abstract


Objective: Neuropsychiatric symptoms including impairment of memory, attention, and executive function are important features of Cushing´s syndrome (CS). Notably, patients with CS in remission commonly demonstrate residual cognitive dysfunction, which has been suggested to be linked to incomplete recovery of neuronal function. Our hypothesis was that functional brain responses are altered during cognitive testing in patients with CS in remission. view more

Objective: Neuropsychiatric symptoms including impairment of memory, attention, and executive function are important features of Cushing´s syndrome (CS). Notably, patients with CS in remission commonly demonstrate residual cognitive dysfunction, which has been suggested to be linked to incomplete recovery of neuronal function. Our hypothesis was that functional brain responses are altered during cognitive testing in patients with CS in remission.
Design, patients and methods: We included 19 women previously treated for CS (14 Cushing’s disease and 5 cortisol producing adrenal adenomas) and 19 controls, matched for age, gender and education. The median (interquartile range) remission time was 7 (6-10) years. Brain activity was studied with functional magnetic resonance imaging during an episodic-memory face-name task. The primary regions of interest were the prefrontal cortex and the hippocampus. A voxel wise comparison of functional brain responses in patients and controls was performed, and an uncorrected P<0.001 was considered significant.

Results: During memory encoding, patients displayed lower functional brain responses in the left and right prefrontal gyrus (Brodmann areas (BA) 44, 45 and 46) as well as the right inferior occipital gyrus (BA 18) compared to controls (P<0.001 for all). During memory retrieval the patients displayed lower functional brain responses in several brain areas including the prefrontal, parietal, occipital and cerebellar cortices bilaterally. The most predominant difference was found in the right prefrontal cortex (BA 46 and 48; P<0.001). A conjunction analysis revealed that reduced functional response in left dorsolateral prefrontal cortex was seen for patients during both encoding and retrieval. As a region of interest analysis we compared the functional brain responses in four hippocampal clusters that were significantly activated during memory encoding among all participants (P<0.05, FDR). Compared with controls the patients had a trend towards lower functional brain responses in the left anterior hippocampus (P=0.05).

Conclusion: Women with CS in long-term remission have reduced functional brain responses in the prefrontal cortex, and also in the hippocampus, during episodic memory. This observation supports and extends previous findings showing long-term cognitive dysfunction and structural brain changes caused by transient severe hypercortisolemia.

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