Article

Memory impairment in Cushing's disease

Department of Neurology, IRCCS C. Mondino, University of Pavia, Italy.
Acta Neurologica Scandinavica (Impact Factor: 2.44). 02/1993; 87(1):52-5. DOI: 10.1111/j.1600-0404.1993.tb04075.x
Source: PubMed

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.

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    • "Acute administration of exogenous corticosteroids in humans is associated with reversible decline in declarative memory performance (de Quervain et al., 2000; Newcomer et al., 1999). Cushing's disease is associated with memory impairment (Mauri et al., 1993) and hippocampal atrophy (Starkman et al., 1992) that is, at least partially, reversible with normalization of cortisol levels (Starkman et al., 1999; Starkman et al., 2003). We reported that patients receiving long-term prescription corticosteroid therapy had poorer declarative memory, decreased hippocampal volume and decreased temporal lobe levels of N-acetyl aspartate as compared to controls with similar medical histories but minimal corticosteroid exposure (Brown et al., 2004). "
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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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    • "On the other hand, another study [39] concluded that, generally speaking, increased cortisol levels due to stress-induced HPA axis over activity have been associated with cognitive impairment as stress-induced HPA axis overactivity and increased cortisol levels may cause hippocampal damage and, subsequently, cognitive decline. Furthermore, patients with Cushing's syndrome more often present with cognitive impairment [40]. Finally, one of the side-effects of treatment with synthetic corticosteroids is cognitive deterioration [41] "
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    ABSTRACT: Autism is a disorder of early childhood characterized by social impairment, communication abnormalities and stereotyped behaviors. The hypothalamic-pituitary-adrenocortical (HPA) axis deserves special attention, since it is the basis for emotions and social interactions that are affected in autism. To assess basal and stimulated plasma cortisol, and adrenocorticotropic hormone (ACTH) levels in autistic children and their relationship to disease characteristics. Fifty autistic children were studied in comparison to 50 healthy age-, sex- and pubertal stage- matched children. All subjects were subjected to clinical evaluation and measurement of plasma cortisol (basal and stimulated) and ACTH. In addition, electroencephalography (EEG) and intelligence quotient (IQ) assessment were done for all autistic children. Sixteen% of autistic patients had high ACTH, 10% had low basal cortisol and 10% did not show adequate cortisol response to ACTH stimulation. Autistic patients had lower basal (p = 0.032) and stimulated cortisol (p = 0.04) and higher ACTH (p = 0.01) than controls. Childhood Autism Rating Scale (CARS) score correlated positively with ACTH (r = 0.71, p = 0.02) and negatively with each of basal (r = -0.64, p = 0.04) and stimulated cortisol (r = -0.88, p < 0.001). Hormonal profile did not differ in relation to EEG abnormalities, IQ and self- aggressive symptoms. The observed hormonal changes may be due to a dysfunction in the HPA axis in autistic individuals. Further studies are warranted regarding the role of HPA axis dysfunction in the pathogenesis of autism.
    Italian Journal of Pediatrics 10/2010; 36(1):71. DOI:10.1186/1824-7288-36-71 · 1.52 Impact Factor
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    • "Although the hippocampal and memory effects of GC have been the prime focus in the literature and some suggest that the cognitive deficits in CS patients are more frequent and more severe in verbal and visual memory (Martignoni et al., 1992), various cognitive disturbances have been associated with CS (Bourdeau et al., 2005; Dorn & Cerrone, 2000; Forget, Lacroix, Somma, & Cohen, 2000; Mauri et al., 1993; Starkman, Giordani, Berent, Schork, & Schteingart, 2001). Compared to controls, CS subjects show a poorer general intellectual performance (IQ scores) and impairment in tests of visual and spatial information, attention , reasoning and verbal fluency (Mauri et al., 1993; Starkman et al., 2001). These results and the fact that there is a high density of glucocorticoid receptors throughout the brain suggests a pathophysiologic role of GCs in CS that extends beyond specific effects on memory and learning, involving other brain structures than the hippocampus. "
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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.
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