Long-Term Cognitive Impairments and Attentional Deficits in Patients with Cushing's Disease and Cortisol-Producing Adrenal Adenoma in Remission

Department of Endocrinology, Gröna Stråket 8, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. .
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 07/2012; 97(9):E1640-8. DOI: 10.1210/jc.2012-1945
Source: PubMed


Context: Cognitive function is impaired in patients with active Cushing's syndrome (CS). Objective: The aim was to study cognitive function in patients with CS in long-term remission. Design: We conducted a cross-sectional, case-controlled, single center study. Patients: Fifty-five patients previously treated for Cushing's disease (n = 43) and cortisol-producing adrenal adenoma (n = 12) and 55 controls matched for age, gender, and educational level participated in the study. Methods: Working memory, attention, information-processing speed, verbal fluency, and reading speed were studied using standardized neuropsychological testing and alerting, orienting, and executive control using the Attentional Network Test. Fatigue impact scale and the comprehensive psychopathological rating scale were used to evaluate fatigue and affective disorder. Results: Median (interquartile range) duration of remission was 13 (5-19) yr and the mean ± sd age at follow-up was 54 ± 14 yr. Compared to controls, patients had a higher score on the fatigue impact scale, indicating greater burdens of fatigue, and a higher score on the comprehensive psychopathological rating scale subscales for depression and anxiety. In a multivariate analysis, attention, spatial orienting, alerting, working memory, verbal fluency, and reading speed were all diminished in comparison to controls, independent of scores for affective disorder and fatigue. No overall difference in outcome was seen between patients in long-term remission for Cushing's disease and cortisol-producing adrenal adenoma. Conclusion: Patients with CS in remission have impaired cognitive function that cannot be explained by the coexistence of affective disorder or chronic fatigue. The pattern of cognitive and attentional deficits suggests a more global involvement of the brain function than has previously been suggested.

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    • "cortisol in humans) can either damage the brain directly (Uno et al., 1994; Sapolsky et al., 1990) or potentiate the action of other damaging agents, including b-amyloid (Magarinos et al., 1996, 1998; Sapolsky, 1996; Goodman et al., 1996; Tombaugh et al., 1992), whereas blockade of GCs is protective. For example, the hypercortisolism of Cushing's disease decreases hippocampal and frontal lobe volume (Starkman, 2013; Starkman et al., 1992) and results in long-term reductions in white matter and impaired cognitive function long after remission (van der Werff et al., 2014; Ragnarsson et al., 2012). A reduction in hippocampal volume is has been repeatedly reported in MDD, but considerable variation exists in the literature. "
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