Journal of Neural Transmission

, Volume 126, Issue 3, pp 219–232 | Cite as

Cortisol levels, motor, cognitive and behavioral symptoms in Parkinson’s disease: a systematic review

  • Nayron Medeiros SoaresEmail author
  • Gabriela Magalhães Pereira
  • Vivian Altmann
  • Rosa Maria Martins de Almeida
  • Carlos R. M. Rieder
Neurology and Preclinical Neurological Studies - Review Article


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.


Parkinson disease Neurodegenerative disease Hydrocortisone Cortisol Hypothalamic–pituitary axis Stress 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Aarsland D, Marsh L, Schrag A (2009) Neuropsychiatric symptoms in Parkinson’s disease. Mov Disord 24(15):2175–2186. CrossRefGoogle Scholar
  2. Alatriste-Booth V, Rodríguez-Violante M, Camacho-Ordoñez A, Cervantes-Arriaga A (2015) Prevalence and correlates of sleep disorders in Parkinson’s disease: a polysomnographic study. Arq Neuropsiquiatr 73(3):241–245. CrossRefGoogle Scholar
  3. Alves G, Forsaa EB, Pedersen KF, Dreetz Gjerstad M, Larsen JP (2008) Epidemiology of Parkinson’s disease. J Neurol 5:18–32. CrossRefGoogle Scholar
  4. Ambrosi G, Cerri S, Blandini F (2014) A further update on the role of excitotoxicity in the pathogenesis of Parkinson’s disease. J Neural Transm (Vienna) 121(8):849–859. CrossRefGoogle Scholar
  5. 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. CrossRefGoogle Scholar
  6. Bellomo G, Santambrogio L, Fiacconi M, Scarponi AM, Ciuffetti G (1991) Plasma profiles of adrenocorticotropic hormone, cortisol, growth hormone and prolactin in patients with untreated Parkinson’s disease. J Neurol 238(1):19–22. CrossRefGoogle Scholar
  7. Blesa J, Trigo-Damas I, Quiroga-Varela A, Jackson-Lewis VR (2015) Oxidative stress and Parkinson’s disease. Front Neuroanat 9:91. Google Scholar
  8. 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. CrossRefGoogle Scholar
  9. Bordet R, Devos D, Brique S, Touitou Y, Guieu JD, Libersa C, Destée A (2003) Study of circadian melatonin secretion pattern at different stages of Parkinson’s disease. Clin Neuropharmacol 26(2):65–72. CrossRefGoogle Scholar
  10. Breen DP, Vuono R, Nawarathna U, Fisher K, Shneerson JM, Reddy AB, Barker RA (2014) Sleep and circadian rhythm regulation in early Parkinson disease. JAMA Neurol 71(5):589–595. CrossRefGoogle Scholar
  11. Bremmer MA, Deeg DJ, Beekman AT, Penninx BW, Lips P, Hoogendijk WJ (2007) Major depression in late life is associated with both hypo- and hypercortisolemia. Biol Psychiatry 62(5):479–486. CrossRefGoogle Scholar
  12. Bury AG, Pyle A, Elson JL, Greaves L, Morris CM, Hudson G, Pienaar IS (2017) Mitochondrial DNA changes in pedunculopontine cholinergic neurons in Parkinson disease. Ann Neurol 82(6):1016–1021. CrossRefGoogle Scholar
  13. Cash TV, Lageman SK (2015) Randomized controlled expressive writing pilot in individuals with Parkinson’s disease and their caregivers. BMC Psychol 3:44. CrossRefGoogle Scholar
  14. Chan S, Debono M (2010) Replication of cortisol circadian rhythm: new advances in hydrocortisone replacement therapy. Ther Adv Endocrinol Metab 1(3):129–138. CrossRefGoogle Scholar
  15. Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39(6):889–909CrossRefGoogle Scholar
  16. 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
  17. Djamshidian A, Lees AJ (2014) Can stress trigger Parkinson’s disease? J Neurol Neurosurg Psychiatry 85:878–881. CrossRefGoogle Scholar
  18. Djamshidian A, O’Sullivan SS, Papadopoulos A, Bassett P, Shaw K, Averbeck BB, Lees A (2011) Salivary cortisol levels in Parkinson’s disease and its correlation to risk behaviour. J Neurol Neurosurg Psychiatry 82:1107–1111. CrossRefGoogle Scholar
  19. Dorszewska J, Prendecki M, Lianeri M, Kozubski W (2014) Molecular effects of L-dopa therapy in Parkinson’s disease. Curr Genom 15:11–17. CrossRefGoogle Scholar
  20. 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. CrossRefGoogle Scholar
  21. Grünblatt E, Ruder J, Monoranu CM, Riederer P, Youdim MB, Mandel SA (2017) Mandel, differential alterations in metabolism and proteolysis-related proteins in human Parkinson’s disease Substantia nigra. Neurotox Res 33(3):560–568. CrossRefGoogle Scholar
  22. Håglin L, Bäckman L (2016) Covariation between plasma phosphate and daytime cortisol in early Parkinson’s disease. Brain Behav 6(12):e00556. CrossRefGoogle Scholar
  23. Happe S, Tings T, Helmschmied K, Neubert K, Wuttke W, Paulus W, Trenkwalder C (2004) Levodopa treatment does not affect low-dose apomorphine test in patients with Parkinson’s disease. Mov Disord 19(12):1511–1515. CrossRefGoogle Scholar
  24. 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. CrossRefGoogle Scholar
  25. Ibrahimagic OC, Jakubovic AC, Smajlovic D, Dostovic Z, Kunic S, Iljazovic A (2016) Psychological stress and changes of hypothalamic–pituitary–adrenal axis in patients with “De Novo” Parkinson’s disease. Med Arch 70(6):445–448. CrossRefGoogle Scholar
  26. Kabia FM, Rhebergen D, van Exel E, Stek ML, Comijs HC (2016) The predictve value of cortsol levels on 2-year course of depression in older persons. Psychoneuroendocrinology 63:320–326. CrossRefGoogle Scholar
  27. Kanner AM (2004) Is major depression a neurologic disorder with psychiatric symptoms? Epilepsy Behav 5(5):636–644. CrossRefGoogle Scholar
  28. Kibel A, Drenjančević-Perić I (2008) Impact of glucocorticoids and chronic stress on progression of Parkinson′s disease. Med Hypotheses 71(6):952–956. CrossRefGoogle Scholar
  29. Kluen LM, Agorastos A, Wiedemann K, Schwabe L (2017) Cortisol boosts risky decision-making behavior in men but not in women. Psychoneuroendocrinology 84:181–189. CrossRefGoogle Scholar
  30. Lemke MR (2008) Depressive symptoms in Parkinson’s disease. Eur J Neurol 1:21–25. CrossRefGoogle Scholar
  31. Levy OA, Malagelada C, Greene LA (2009) Greene, Cell death pathways in Parkinson’s disease: proximal triggers, distal effectors, and final steps. Apoptosis 14(4):478–500. CrossRefGoogle Scholar
  32. 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. CrossRefGoogle Scholar
  33. Marakaki C, Papadimitriou DT, Kleanthous K, Papadopoulou A, Papadimitriou A (2015) L-Dopa stimulates cortisol secretion through adrenocorticotropic hormone release in short children. Horm Res Paediatr 84(5):319–322. CrossRefGoogle Scholar
  34. Maripuu M, Wikgren M, Karling P, Adolfsson R, Norrback KF (2014) Relative hypo- and hypercortisolism are both associated with depression and lower quality of life in bipolar disorder: a cross-sectional study. PLoS One 9(6):e98682. CrossRefGoogle Scholar
  35. Menza M, Dobkin RD, Marin H, Mark MH, Gara M, Bienfait K, Dicke A, Kusnekov A (2010) The role of inflammatory cytokines in cognition and other non-motor symptoms of Parkinson’s disease. Psychosomatics 51:474–479. Google Scholar
  36. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) The PRISMA group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097. CrossRefGoogle Scholar
  37. Moore H, Rose HJ, Grace AA (2001) Chronic cold stress reduces the spontaneous activity of ventral tegmental dopamine neurons. Neuropsychopharmacology 24:410–419. CrossRefGoogle Scholar
  38. Moreira RC, Zonta MB, Araújo APS, Israel VL, Teive HAG (2017) Quality of life in Parkinson’s disease patients: progression markers of mild to moderate stages. Arq Neuropsiquiatr 75:497–502. CrossRefGoogle Scholar
  39. Müller T, Muhlack S (2007) Acute levodopa intake and associated cortisol decrease in patients with Parkinson disease. Clin Neuropharmacol 30:101–106. CrossRefGoogle Scholar
  40. Müller T, Welnic J, Muhlack S (2007) Acute levodopa administration reduces cortisol release in patients with Parkinson’s disease. J Neural Transm 114:347–350. CrossRefGoogle Scholar
  41. 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
  42. Pereira GM, Soares NM, Souza AR de, Becker J, Finkelsztejn A, Almeida RMM (2018) Basal cortisol levels and the relationship with clinical symptoms in multiple sclerosis: a systematic review. Arq Neuropsiquiatr 76(9):622–634. CrossRefGoogle Scholar
  43. Růžička F, Jech R, Nováková L, Urgošík D, Bezdíček O, Vymazal J, Růžička E (2015) Chronic stress-like syndrome as a consequence of medial site subthalamic stimulation in Parkinson’s disease. Psychoneuroendocrinology 52:302–310. CrossRefGoogle Scholar
  44. Schapira AH, Jenner P (2011) Etiology and pathogenesis of Parkinson's disease. Mov Disord 26(6):1049–1055. CrossRefGoogle Scholar
  45. 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. CrossRefGoogle Scholar
  46. Stypuła G, Kunert-Radek J, Stepień H, Zylińska K, Pawlikowski M (1996) Evaluation of interleukins, ACTH, cortisol and prolactin concentrations in the blood of patients with parkinson’s disease. Neuroimmunomodulation 3(2–3):131–134. CrossRefGoogle Scholar
  47. Tysnes OB, Storstein A (2017) Epidemiology of Parkinson’s disease. J Neural Transm 124:901. CrossRefGoogle Scholar
  48. Vardi J, Oberman Z, Rabey I, Streifler M, Ayalon D, Herzberg M (1976) Weight loss in patients treated long-term with levodopa. Metabolic aspects. J Neurol Sci 30(1):33–40. CrossRefGoogle Scholar
  49. Vogel HP, Ketsche R (1986) Effect of hypoglycaemia, TRH and levodopa on plasma growth hormone, prolactin, thyrotropin and cortisol in Parkinson’s disease before and during therapy. J Neurol 233(3):149–152. CrossRefGoogle Scholar
  50. Volpi R, Caffarra P, Boni S, Scaglioni A, Malvezzi L, Saginario A, Chiodera P, Coiro V (1997) ACTH/cortisol involvement in the serotonergic disorder affecting the parkinsonian brain. Neuropsychobiology 35(2):73–78. CrossRefGoogle Scholar
  51. Vyas S, Rodrigues AJ, Silva JM, Tronche F, Almeida OFX, Sousa N, Sotiropoulos I (2016) Chronic stress and glucocorticoids: from neuronal plasticity to neurodegeneration. Neural Plast. Google Scholar
  52. 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. CrossRefGoogle Scholar
  53. Zhang G, Zhang Z, Liu L, Yang J, Huang J, Xiong N, Wang T (2014) Impulsive and compulsive behaviors in Parkinson’s disease. Front Aging Neurosci 6:318. Google Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Medical Science Post Graduation ProgramFederal University of Rio Grande do SulPorto AlegreBrazil
  2. 2.Institute of Basic Health SciencesFederal University of Rio Grande do Sul (UFRGS)Porto AlegreBrazil
  3. 3.Institute of BiosciencesFederal University of Rio Grande do SulPorto AlegreBrazil
  4. 4.Institute of Psychology, Laboratory of Psychology, Neuroscience and Behavior (LPNeC)Federal University of Rio Grande do SulPorto AlegreBrazil
  5. 5.Hospital de Clinicas de Porto Alegre (HCPA)Porto AlegreBrazil
  6. 6.Federal University of Health Science of Porto Alegre (UFCSPA)Porto AlegreBrazil

Personalised recommendations