Memory impairment in Cushing's disease.
ABSTRACT In the present study the cognitive performance of 25 patients with Cushing's disease (CD) was extensively evaluated in comparison with normal control subjects, matched one by one. The results indicate a selective impairment of memory functions: the number of patients showing a significantly impaired mnesic performance increases with age. Moreover, the neuropsychological impairment tends to recover in those cases who underwent further controls after surgical treatment. The neuropsychological data are discussed in the light of recent evidence in the literature concerning the effects of adrenal steroids on the brain.
Full-textDOI: · Available from: Roberto Attanasio, Jun 23, 2015
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ABSTRACT: An extensive animal literature suggests that stress or excessive corticosteroid exposure is associated with changes in hippocampal function and memory. These findings are pertinent to psychiatric disorders with elevated cortisol, Cushing's disease and the millions of patients receiving prescription corticosteroids. In animals, agents that decrease glutamate release attenuate the effects of corticosteroids on the hippocampus. Minimal data are available on preventing or reversing the effects of corticosteroids on the human hippocampus. We previously reported improvement in memory in corticosteroid-treated patients given lamotrigine. In this report, we examined the impact of lamotrigine on task-related hippocampal activation in patients taking prescription corticosteroids. A total of 28 outpatients taking long-term oral prednisone for medical conditions, such as renal transplant rejection, were randomized to lamotrigine or placebo for 24 weeks. Hippocampal activation in response to a visual memory task was assessed with blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). Consistent with a reduction in glutamate release, the right posterior hippocampus showed a significant decrease in task-related activation in the lamotrigine group as compared to the placebo group. The modest sample size and an assessment period of only 24 weeks are study limitations. Between-group differences in hippocampal activation were observed. The results suggest that an agent that modulates glutamate may modify the effects of long-term corticosteroid exposure on the human hippocampus.Journal of Affective Disorders 11/2010; 126(3):415-9. DOI:10.1016/j.jad.2010.04.010 · 3.71 Impact Factor
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ABSTRACT: Cumulative exposure to glucocorticoid hormones (GC) over the lifespan has been associated with cognitive impairment and may contribute to physical and cognitive degeneration in aging. The objective of the present study was to examine whether the pattern of cognitive deficits in patients with Cushing's syndrome (CS), a disorder characterized by chronic exposure to elevated levels of glucocorticoids (GC), is similar to that observed in older individuals. Ten subjects with CS were compared to sex-, age-, and education-matched healthy controls and older subjects (age of CS subjects+15 yr). All participants were administered tests to assess attention, visuospatial processing, learning and memory, reasoning, concept formation and verbal fluency. MANCOVAs with depression scores as covariate and polynomial contrasts revealed that the age-matched control group performed better than the CS and older subject groups in visual target detection, trail making test, stroop task, digit symbol substitution, block design, object assembly, visual reproduction, spatial memory and similarities. The CS and older subjects performed similarly on these tasks. Further, a principal component analysis revealed two significant factors, representing general cognitive function and verbal memory explaining 39.9% and 10.0% of the variance, respectively. Additional MANCOVAs with depression as a covariate revealed that CS and older control subjects showed impaired performance on general cognitive function compared to age-matched controls. These results suggest that hypersecretion of GCs has "aging-like" effects on cognitive performance in individuals with CS.Brain and Cognition 06/2009; 71(1):1-8. DOI:10.1016/j.bandc.2009.02.013 · 2.68 Impact Factor
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ABSTRACT: An extensive animal literature suggests that excessive corticosteroid exposure is associated with changes in memory and the hippocampus. Agents that decrease glutamate attenuate corticosteroid effects on the hippocampus. Minimal data are available on preventing or reversing corticosteroid effects on the human hippocampus. We previously reported that open-label lamotrigine was associated with significant improvement in declarative memory in corticosteroid-treated patients. We now examine the impact of 24 weeks of randomized, placebo-controlled lamotrigine therapy on declarative memory (primary aim) and hippocampal volume (secondary aim) in 28 patients (n=16 for lamotrigine, n=12 for placebo) taking prescription corticosteroids. All participants with data from at least one postbaseline assessment (n=9 for lamotrigine, n=11 for placebo) were included in the analysis. Declarative memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT) at baseline and weeks 12 and 24. Hippocampal and total brain volumes were manually traced from MRI scans obtained at baseline and week 24. On the basis of an ANCOVA analysis, total words learned on the RAVLT at exit were significantly greater in the lamotrigine group (n=8, missing data or dropouts n=8) compared to the placebo group (n=11, dropout n=1). RAVLT scores in the lamotrigine group increased from mildly impaired to average range. Hippocampal volume changes were small in both lamotrigine (n=7) and placebo (n=7) groups during the 24-week assessment period and between-group differences were not significant. Results suggest that lamotrigine may improve declarative memory in patients taking prescription corticosteroids although differential dropout rate in the two groups is a concern.Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 12/2007; 33(10):2376-83. DOI:10.1038/sj.npp.1301627 · 7.83 Impact Factor