Cortisol levels, motor, cognitive and behavioral symptoms in Parkinson’s disease: a systematic review
Parkinson’s disease (PD) is a progressive and multifactorial neurodegenerative disease. It has been suggested that a dysregulation of the hypothalamic–pituitary–adrenal axis (HPA) occurs in PD. Furthermore, this dysregulation may be involved in triggering, exacerbation or progression of disease. The objective of this study was to systematically review the literature regarding cortisol levels and their relation with motor, cognitive and behavioral symptoms in patients with PD. A systematic search was performed in PubMed and Embase databases, according to PRISMA norms. Twenty-one studies were included, which evaluated baseline levels of cortisol and motor, cognitive, behavioral symptoms, drugs administration or deep brain stimulation to PD treatment. Sample size ranged from 7 to 249 individuals. In 14 studies that assessed cortisol levels in PD patients, seven showed elevation of cortisol levels. In relation to symptomatology, high levels of cortisol were associated with worst functional scores evaluated by UPDRS, depression and behavior in risk preference. Medication interactions showed an influence on the regulation of cortisol release, mainly, conventional drugs used in the PD’s treatment, such as levodopa. The results found in this review point to a possible relationship between cortisol levels and symptoms in PD, indicating that an HPA axis dysfunction related to cortisol level occurs in PD.
KeywordsParkinson disease Neurodegenerative disease Hydrocortisone Cortisol Hypothalamic–pituitary axis Stress
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Conflict of interest
The authors declare that they have no conflict of interest.
- Augustine EF, Pérez A, Dhall R, Umeh CC, Videnovic A, Cambi F, Wills AM, Elm JJ, Zweig RM, Shulman LM, Nance MA, Bainbridge J, Suchowersky O (2015) Sex differences in clinical features of early, treated Parkinson’s disease. PLoS One 10(7):e0133002. https://doi.org/10.1371/journal.pone.0133002 CrossRefGoogle Scholar
- Bocharov EV, Ivanova-Smolenskaya IA, Poleshchuk VV, Kucheryanu VG, Il’enko VA, Bocharova OA (2010) Therapeutic efficacy of the neuroprotective plant adaptogen in neurodegenerative disease (Parkinson’s disease as an example). Bull Exp Biol Med 149(6):682–684. https://doi.org/10.1007/s10517-010-1023-z CrossRefGoogle Scholar
- Demaagd G, Philip A (2015) Parkinson’s Disease and its management: Part 1: disease entity, risk factors, pathophysiology, clinical presentation, and diagnosis. Pharm Ther 40(8):504–532Google Scholar
- Gruden MA, Sewell RD, Yanamandra K, Davidova TV, Kucheryanu VG, Bocharov EV, Bocharova OA, Polyschuk VV, Sherstnev VV, Morozova-Roche LA (2011) Immunoprotection against toxic biomarkers is retained during Parkinson’s disease progression. J Neuroimmunol 233(1–2):221–227. https://doi.org/10.1016/j.jneuroim.2010.12.001 CrossRefGoogle Scholar
- Hartmann A, Veldhuis JD, Deuschle M, Standhardt H, Heuser I (1997) Twenty-four hour cortisol release profiles in patients with Alzheimer’s and Parkinson’s disease compared to normal controls: ultradian secretory pulsatility and diurnal variation. Neurobiol Aging 18(3):285–289. https://doi.org/10.1016/S0197-4580(97)80309-0 CrossRefGoogle Scholar
- Li SY, Wang YL, Liu WW, Lyu DJ, Wang F, Mao CJ, Yang YP, Hu LF, Liu CF (2017) Long-term levodopa treatment accelerates the circadian rhythm dysfunction in a 6-hydroxydopamine rat model of Parkinson’s disease. Chin Med J 130(9):1085–1092. https://doi.org/10.4103/0366-6999.204920 CrossRefGoogle Scholar
- Müller T, Muhlack S (2007) Acute levodopa intake and associated cortisol decrease in patients with Parkinson disease. Clin Neuropharmacol 30:101–106. https://doi.org/10.1097/01.WNF.0000240954.72186.91 CrossRefGoogle Scholar
- Novakova L, Haluzik M, Jech R, Urgosik D, Ruzicka F, Ruzicka E (2011) Hormonal regulators of food intake and weight gain in Parkinson’s disease after subthalamic nucleus stimulation. Neuro Endocrinol Lett 32:437–441Google Scholar
- Seifried C, Boehncke S, Heinzmann J, Baudrexel S, Weise L, Gasser T, Eggert K, Fogel W, Baas H, Badenhoop K, Steinmetz H, Hilker R (2013) Diurnal variation of hypothalamic function and chronic subthalamic nucleus stimulation in Parkinson’s disease. Neuroendocrinology 97:283–290. https://doi.org/10.1159/000343808 CrossRefGoogle Scholar
- Walker DG, Lue LF, Serrano G, Adler CH, Caviness JN, Sue LI, Beach TG (2015) Altered expression patterns of inflammation-associated and trophic molecules in Substantia nigra and Striatum brain samples from Parkinson’s disease, incidental Lewy body disease and normal control cases. Front Neurosci 9:507. https://doi.org/10.3389/fnins.2015.00507 CrossRefGoogle Scholar