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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    ABSTRACT: OBJECTIVE: Patients with Cushing's syndrome (CS) in long-term remission have impaired cognitive function. Cerebrospinal fluid (CSF) biomarkers are important diagnostic tools in the work-up of patients with cognitive impairment. The aim of this study was to analyze neurodegenerative and inflammatory biomarkers in CSF from patients with CS in remission. DESIGN: A cross-sectional, single centre study. PATIENTS: Twelve women previously treated for CS and six healthy subjects. MEASUREMENTS: Neurodegenerative CSF markers; total tau, hyperphosphorylated tau, amyloid beta peptides, soluble amyloid precursor protein alpha and beta, neurofilament light proteins, glial fibrillary acidic protein and monocyte chemoattractant protein 1, and inflammatory CSF markers; interferon-gamma, Interleukin (IL)-1B, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, IL-13 and tumour necrosis factor alpha. RESULTS: The mean age (mean ± SD) was similar in patients with CS in remission (44.9 ± 14 years) and healthy subjects (42.3 ± 15.7 years; P = 0.726). No differences were seen in concentrations of any neurodegenerative biomarkers between patients and healthy subjects. Nor was the concentration of inflammatory biomarkers different between the groups. CONCLUSIONS: The pattern of neurodegenerative and inflammatory biomarkers in CSF from patients with CS in remission does not differ from healthy subjects. The underlying mechanisms of the cognitive deficits in CS in remission are different from those seen in neurodegenerative disorders and remains to be explained.
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