Widespread Reductions of White Matter Integrity in Patients with Long-term Remission of Cushing's Disease

Overview

Journal Neuroimage Clin

Publisher Elsevier

Specialties Neurology
Radiology

Date 2014 Jun 18

PMID 24936417

Citations 45

Authors

Steven J A van der Werff

Cornelie D Andela

J Nienke Pannekoek

Onno C Meijer

Mark A van Buchem

Serge A R B Rombouts

Roos C van der Mast

Nienke R Biermasz

Alberto M Pereira

Nic J A Van der Wee

Affiliations

Soon will be listed here.

Abstract

Background: Hypercortisolism leads to various physical, psychological and cognitive symptoms, which may partly persist after the treatment of Cushing's disease. The aim of the present study was to investigate abnormalities in white matter integrity in patients with long-term remission of Cushing's disease, and their relation with psychological symptoms, cognitive impairment and clinical characteristics.

Methods: In patients with long-term remission of Cushing's disease (n = 22) and matched healthy controls (n = 22) we examined fractional anisotropy (FA) values of white matter in a region-of-interest (ROI; bilateral cingulate cingulum, bilateral hippocampal cingulum, bilateral uncinate fasciculus and corpus callosum) and the whole brain, using 3 T diffusion tensor imaging (DTI) and a tract-based spatial statistics (TBSS) approach. Psychological and cognitive functioning were assessed with validated questionnaires and clinical severity was assessed using the Cushing's syndrome Severity Index.

Results: The ROI analysis showed FA reductions in all of the hypothesized regions, with the exception of the bilateral hippocampal cingulum, in patients when compared to controls. The exploratory whole brain analysis showed multiple regions with lower FA values throughout the brain. Patients reported more apathy (p = .003) and more depressive symptoms (p < .001), whereas depression symptom severity in the patient group was negatively associated with FA in the left uncinate fasciculus (p < 0.05). Post-hoc analyses showed increased radial and mean diffusivity in the patient group.

Conclusion: Patients with a history of endogenous hypercortisolism in present remission show widespread changes of white matter integrity in the brain, with abnormalities in the integrity of the uncinate fasciculus being related to the severity of depressive symptoms, suggesting persistent structural effects of hypercortisolism.

Citing Articles

Hypothalamic-pituitary-adrenal axis in anorexia nervosa; an underestimated endocrine dysfunction among adolescents.

Calcaterra V, Magenes V, Fratangeli N, Nigro G, Fabiano V, Mendolicchio L Front Pediatr. 2024; 12:1415061.

PMID: 39726537 PMC: 11669515. DOI: 10.3389/fped.2024.1415061.

Reversibility of Impaired Large-Scale Functional Brain Networks in Cushing's Disease after Surgery Treatment: A Longitudinal Study.

Cheng H, Gao L, Jing R, Hou B, Guo X, Yao Y Neuroendocrinology. 2023; 114(3):250-262.

PMID: 37913760 PMC: 10911171. DOI: 10.1159/000534789.

Association between use of systemic and inhaled glucocorticoids and changes in brain volume and white matter microstructure: a cross-sectional study using data from the UK Biobank.

van der Meulen M, Amaya J, Dekkers O, Meijer O BMJ Open. 2022; 12(8):e062446.

PMID: 36041764 PMC: 9438037. DOI: 10.1136/bmjopen-2022-062446.

Long-term effects of glucocorticoid excess on the brain.

Dekkers A, Amaya J, van der Meulen M, Biermasz N, Meijer O, Pereira A J Neuroendocrinol. 2022; 34(8):e13142.

PMID: 35980208 PMC: 9541651. DOI: 10.1111/jne.13142.

Altered hippocampal volume and functional connectivity in patients with Cushing's disease.

Li C, Zhang Y, Wang W, Zhou T, Yu X, Tao H Brain Behav. 2022; 12(6):e2507.

PMID: 35506636 PMC: 9226821. DOI: 10.1002/brb3.2507.

References

Rush A, Gullion C, Basco M, Jarrett R, Trivedi M . The Inventory of Depressive Symptomatology (IDS): psychometric properties. Psychol Med. 1996; 26(3):477-86. DOI: 10.1017/s0033291700035558. View

SNAITH R, Harrop F, Newby D, Teale C . Grade scores of the Montgomery-Asberg Depression and the Clinical Anxiety Scales. Br J Psychiatry. 1986; 148:599-601. DOI: 10.1192/bjp.148.5.599. View

Chatterjee A, Anderson K, Moskowitz C, Hauser W, Marder K . A comparison of self-report and caregiver assessment of depression, apathy, and irritability in Huntington's disease. J Neuropsychiatry Clin Neurosci. 2005; 17(3):378-83. DOI: 10.1176/jnp.17.3.378. View

Starkman M, Giordani B, Gebarski S, Schteingart D . Improvement in learning associated with increase in hippocampal formation volume. Biol Psychiatry. 2003; 53(3):233-8. DOI: 10.1016/s0006-3223(02)01750-x. View

Brown E, Suppes T . Mood symptoms during corticosteroid therapy: a review. Harv Rev Psychiatry. 1998; 5(5):239-46. DOI: 10.3109/10673229809000307. View

van Rossum E, de Jong F, Koper J, Uitterlinden A, Prins N, van Dijk E . Glucocorticoid receptor variant and risk of dementia and white matter lesions. Neurobiol Aging. 2006; 29(5):716-23. DOI: 10.1016/j.neurobiolaging.2006.11.016. View

Tiemensma J, Kokshoorn N, Biermasz N, Keijser B, Wassenaar M, Middelkoop H . Subtle cognitive impairments in patients with long-term cure of Cushing's disease. J Clin Endocrinol Metab. 2010; 95(6):2699-714. DOI: 10.1210/jc.2009-2032. View

Merke D, Giedd J, Keil M, Mehlinger S, Wiggs E, Holzer S . Children experience cognitive decline despite reversal of brain atrophy one year after resolution of Cushing syndrome. J Clin Endocrinol Metab. 2005; 90(5):2531-6. DOI: 10.1210/jc.2004-2488. View

Newell-Price J, Bertagna X, Grossman A, Nieman L . Cushing's syndrome. Lancet. 2006; 367(9522):1605-17. DOI: 10.1016/S0140-6736(06)68699-6. View

10.

Starkstein S, Petracca G, Chemerinski E, Kremer J . Syndromic validity of apathy in Alzheimer's disease. Am J Psychiatry. 2001; 158(6):872-7. DOI: 10.1176/appi.ajp.158.6.872. View

11.

Horsfield M, Jones D . Applications of diffusion-weighted and diffusion tensor MRI to white matter diseases - a review. NMR Biomed. 2002; 15(7-8):570-7. DOI: 10.1002/nbm.787. View

12.

Bourdeau I, Bard C, Noel B, Leclerc I, Cordeau M, Belair M . Loss of brain volume in endogenous Cushing's syndrome and its reversibility after correction of hypercortisolism. J Clin Endocrinol Metab. 2002; 87(5):1949-54. DOI: 10.1210/jcem.87.5.8493. View

13.

Michaud K, Forget H, Cohen H . Chronic glucocorticoid hypersecretion in Cushing's syndrome exacerbates cognitive aging. Brain Cogn. 2009; 71(1):1-8. DOI: 10.1016/j.bandc.2009.02.013. View

14.

Miyata S, Koyama Y, Takemoto K, Yoshikawa K, Ishikawa T, Taniguchi M . Plasma corticosterone activates SGK1 and induces morphological changes in oligodendrocytes in corpus callosum. PLoS One. 2011; 6(5):e19859. PMC: 3104997. DOI: 10.1371/journal.pone.0019859. View

15.

Alexander A, Lee J, Lazar M, Field A . Diffusion tensor imaging of the brain. Neurotherapeutics. 2007; 4(3):316-29. PMC: 2041910. DOI: 10.1016/j.nurt.2007.05.011. View

16.

Kieseppa T, Eerola M, Mantyla R, Neuvonen T, Poutanen V, Luoma K . Major depressive disorder and white matter abnormalities: a diffusion tensor imaging study with tract-based spatial statistics. J Affect Disord. 2009; 120(1-3):240-4. DOI: 10.1016/j.jad.2009.04.023. View

17.

Starkman M, Gebarski S, Berent S, Schteingart D . Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing's syndrome. Biol Psychiatry. 1992; 32(9):756-65. DOI: 10.1016/0006-3223(92)90079-f. View

18.

Dedovic K, DAguiar C, Pruessner J . What stress does to your brain: a review of neuroimaging studies. Can J Psychiatry. 2009; 54(1):6-15. DOI: 10.1177/070674370905400104. View

19.

Tiemensma J, Kaptein A, Pereira A, Smit J, Romijn J, Biermasz N . Negative illness perceptions are associated with impaired quality of life in patients after long-term remission of Cushing's syndrome. Eur J Endocrinol. 2011; 165(4):527-35. DOI: 10.1530/EJE-11-0307. View

20.

Tiemensma J, Biermasz N, Middelkoop H, van der Mast R, Romijn J, Pereira A . Increased prevalence of psychopathology and maladaptive personality traits after long-term cure of Cushing's disease. J Clin Endocrinol Metab. 2010; 95(10):E129-41. DOI: 10.1210/jc.2010-0512. View