Patterns of cognitive change over time and relationship to age following successful treatment of Cushing's disease

Hook, Julie N.; Giordani, Bruno; Schteingart, D.E.; Guire, Kenneth E.; Giles, Jodie E.; Ryan, Kelley A.; Gebarśki, Stephen S.; Langenecker, Scott A.; Starkman, Monica N.

doi:10.1017/s1355617707070051

Cited by 65 publications

(56 citation statements)

References 35 publications

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“…Prior studies have looked at cognitive and hippocampal volume changes in patients with Cushing's disease before and after treatment of the hypercortisolemia. Adults with Cushing's disease demonstrate improvement in some, but not all, cognitive domains following normalization of cortisol levels (Hook et al, 2007). An increase in hippocampal volume of approximately 3% is reported 17 months after surgical excision of the ACTHsecreting tumor in patients with Cushing's disease (Starkman et al, 1999(Starkman et al, , 2003.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of the Effects of Corticosteroids on Declarative Memory with Lamotrigine

Brown

Wolfshohl

Shad

et al. 2007

Neuropsychopharmacol

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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 ¼ 16 for lamotrigine, n ¼ 12 for placebo) taking prescription corticosteroids. All participants with data from at least one postbaseline assessment (n ¼ 9 for lamotrigine, n ¼ 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 ¼ 8, missing data or dropouts n ¼ 8) compared to the placebo group (n ¼ 11, dropout n ¼ 1). RAVLT scores in the lamotrigine group increased from mildly impaired to average range. Hippocampal volume changes were small in both lamotrigine (n ¼ 7) and placebo (n ¼ 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.

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Section: Discussionmentioning

confidence: 99%

Attenuation of the Effects of Corticosteroids on Declarative Memory with Lamotrigine

Brown

Wolfshohl

Shad

et al. 2007

Neuropsychopharmacol

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“…In contrast, Bourdeau et al (15) found no correlation between brain volume and current age, although this could be related to the relatively young sample of patients included. An increase in hippocampal volume was associated with a decrease in UFC after treatment (12,13,21), but not with reduction in plasma cortisol, duration of disease, or the number of months relapsed since treatment (21,30). Increase in right caudate head volume (CHV) was also associated with decrease in UFC, while increase in left CHV and right and left CHV together were not associated with change in UFC (13,21).…”

Section: Associations Between Brain Abnormalities and Clinical Characmentioning

confidence: 96%

“…In adolescents with active CS, left amygdala activation and right anterior hippocampal activation did not correlate with the performance of a facial memory task (26). Increase in hippocampal volume after correction of hypercortisolism was positively associated with improvement in learning (13,30), but change in CHV was not (13,30). An increase in right caudate volume was associated with improvement in mood (depression and anxiety) and related ideation (obsessive-compulsive and paranoid ideation), whereas change in left CHV and hippocampal volume were not correlated with mood or ideation (21).…”

Section: Associations Between Brain Abnormalities and Behavioral Outcmentioning

confidence: 98%

“…One study did neither describe diagnostic nor remission criteria (20). Described diagnostic criteria were clinical features (truncal obesity, skin and muscle arthophy, moon facies) (11,12,13,21), elevated urinary free cortisol (UFC) (11,12,13,21,22,23,24,25,26,27,28,29), elevated cortisol secretion rates (11,12,13,21,23,24,25,30), elevated midnight salivary cortisol (29,31), absence of blunted circadian rhythm of cortisol secretion (11,12,13,21,26,27,30,32,33), elevated ACTH levels (in CD only) (12,13,21,23,24), lack of suppression after low dose dexamethasone ((1 mg) (22,25,29,33), (2 mg) (12,13,21...…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

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MECHANISMS IN ENDOCRINOLOGY: Cushing's syndrome causes irreversible effects on the human brain: a systematic review of structural and functional magnetic resonance imaging studies

Andela

Haalen

Ragnarsson

et al. 2015

European Journal of Endocrinology

147

129

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Background: Cushing's syndrome (CS) is characterized by excessive exposure to cortisol, and is associated with both metabolic and behavioral abnormalities. Symptoms improve substantially after biochemical cure, but may persist during long-term remission. The causes for persistent morbidity are probably multi-factorial, including a profound effect of cortisol excess on the brain, a major target area for glucocorticoids. Objective: To review publications evaluating brain characteristics in patients with CS using magnetic resonance imaging (MRI). Methods: Systematic review of literature published in PubMed, Embase, Web of Knowledge, and Cochrane databases. Results: Nineteen studies using MRI in patients with CS were selected, including studies in patients with active disease, patients in long-term remission, and longitudinal studies, covering a total of 339 unique patients. Patients with active disease showed smaller hippocampal volumes, enlarged ventricles, and cerebral atrophy as well as alterations in neurochemical concentrations and functional activity. After abrogation of cortisol excess, the reversibility of structural and neurochemical alterations was incomplete after long-term remission. MRI findings were related to clinical characteristics (i.e., cortisol levels, duration of exposure to hypercortisolism, current age, age at diagnosis, and triglyceride levels) and behavioral outcome (i.e., cognitive and emotional functioning, mood, and quality of life). Conclusion:Patients with active CS demonstrate brain abnormalities, which only partly recover after biochemical cure, because these still occur even after long-term remission. CS might be considered as a human model of nature that provides a keyhole perspective of the neurotoxic effects of exogenous glucocorticoids on the brain.

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“…For example, prolonged cortisol elevations predict memory dysfunction and reduced volume of the hippocampus and ACC during aging (9,10). Moreover, in patients with Cushing's syndrome, hypercortisolism was associated with smaller hippocampal volumes and overall brain atrophy (11,12,13), with increasing hippocampal volumes and improving emotional and cognitive functioning after correction of hypercortisolism (11,14,15,16,17,18).…”

Section: Introductionmentioning

confidence: 99%

Smaller grey matter volumes in the anterior cingulate cortex and greater cerebellar volumes in patients with long-term remission of Cushing's disease: a case–control study

Andela

Werff

Pannekoek

et al. 2013

European Journal of Endocrinology

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Objective: Patients with long-term remission of Cushing's disease (CD) have persistent psychological and cognitive impairments. It is unknown whether, and to what extent, these impairments are accompanied by structural abnormalities in the brain. We aim to investigate structural changes in the brain in patients with predominantly long-term remission of CD and to examine whether these changes are associated with psychological and cognitive dysfunction and clinical severity. Design: A cross-sectional, case-control study. Methods: In 25 patients with predominantly long-term remission of CD and 25 matched healthy controls, grey matter volumes in the regions of interest (hippocampus, amygdala, and anterior cingulate cortex (ACC)) and in the whole brain were examined, using 3T magnetic resonance imaging and a voxel-based morphometry approach. Psychological and cognitive functioning were assessed using validated questionnaires and clinical severity was assessed using the Cushing's syndrome severity index. Results: Compared with controls, patients had smaller grey matter volumes of areas in the ACC (on average 14%, P!0.05) and greater volume of the left posterior lobe of the cerebellum (on average 34%, P!0.05). As expected, patients with remitted CD reported more depressive symptoms (PZ0.005), more anxiety (PZ0.003), more social phobia (PZ0.034), more apathy (PZ0.002), and more cognitive failure (PZ0.023) compared with controls, but the differences in grey matter volumes were not associated with psychological or cognitive measures, nor with clinical severity. Conclusion: Patients with predominantly long-term remission of CD showed specific structural brain abnormalities, in the presence of psychological dysfunction. Our data form a basis for future work aimed at elucidating the relation of the structural brain abnormalities and the sustained psychological deficits after long-term exposure to high cortisol levels.

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Patterns of cognitive change over time and relationship to age following successful treatment of Cushing's disease

Cited by 65 publications

References 35 publications

Attenuation of the Effects of Corticosteroids on Declarative Memory with Lamotrigine

Attenuation of the Effects of Corticosteroids on Declarative Memory with Lamotrigine

MECHANISMS IN ENDOCRINOLOGY: Cushing's syndrome causes irreversible effects on the human brain: a systematic review of structural and functional magnetic resonance imaging studies

Smaller grey matter volumes in the anterior cingulate cortex and greater cerebellar volumes in patients with long-term remission of Cushing's disease: a case–control study

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