Depression in prodromal Parkinson's disease: a systematic review
DOI:
https://doi.org/10.25118/2763-9037.2025.v15.1507Keywords:
Parkinson disease, depression, depressive symptomsAbstract
Introduction: Parkinson's disease (PD) is marked not only by motor symptoms, but non-motor symptoms such as REM sleep disorder, constipation, anosmia, dysautonomia, depression, anxiety, cognitive impairment and others. It is possible that these symptoms precede bradykinesia, forming a condition called Prodromal PD (PPD). Identifying PPD allows optimization of treatment and care. The identification of these patients with PPD remains a challenge, as many of the symptoms listed are prevalent in the elderly population. Depression is highlighted as a prodromal symptom, but identifying patients with depressive symptoms that are part of PPD is a challenging task. Objectives: to carry out a systematic review of the literature, aiming to identify advances and updates regarding depression in PPD, allowing the identification of patients with depression who are part of the group of patients with PPD. Methods: systematic literature review, following the guidelines of the PRISMA 2020 protocol; searching the descriptors depression, depressive symptoms and prodromal parkinson's disease on the Pubmed Platform. 25 publications were found; In the end, 9 articles remained for inclusion in the review. Results: predictive value was observed in the combination of REM sleep disorder and depression for the development of PD; presence of two or more prodromal symptoms combined represented a predictive factor for PD; hospitalization for depression predicted risk of developing PD. Conclusion: combination of depression and other prodromal symptoms predicts PD, as well as the severity and refractoriness of the depressive condition. Prodromal symptoms remain a challenge, but can be actively investigated.
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1. Alves, GS, Tíbor Rilho P, Sudo FK. Psicogeriatria: Diagnóstico e Manejo. São Paulo: Artmed Editora; 2022.
2. Sommerauer M, Fedorova TD, Hansen AK, Knudsen K, Otto M, Jeppesen J, Frederiksen Y, Blicher JU, Geday J, Nahimi A, Damholdt MF, Brooks DJ, Borghammer P. Evaluation of the noradrenergic system in Parkinson's disease: an 11C-MeNER PET and neuromelanin MRI study. Brain. 2018;141(2):496-504. https://doi.org/10.1093/brain/awx348 PMid:29272343
3. Rascol O, Schelosky L, 123I-metaiodobenzylguanidine scintigraphy in Parkinson's disease and related disorders. Mov Disord. 2009,24(Suppl 2):S732-41. https://doi.org/10.1002/mds.22499 PMID: 19877202
4. Nandhagopal R, Kuramoto L, Schulzer M, Mak E, Cragg J, Lee CS, McKenzie J, McCormick S, Samii A, Troiano A, Ruth TJ, Sossi V, de la Fuente-Fernandez R, Calne DB, Stoessl AJ. Longitudinal progression of sporadic Parkinson's disease: a multi-tracer positron emission tomography study. Brain. 2009;132(Pt 11):2970-9. https://doi.org/10.1093/brain/awp209 PMid:19690093
5. Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology. 1967;17(5):427-42. https://doi.org/10.1212/WNL.17.5.427 PMid:6067254
6. Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, Schrag AE, Lang AE. Parkinson disease. Nat Rev Dis Primers. 2017;3:17013. https://doi.org/10.1038/nrdp.2017.13 PMid:28332488
7. Lewy FH. Paralysis agitans. I. Pathologische Anatomie. In: Lewandowsky M. editor. Handbuch der Neurologie. Berlin: Springer; 1912. p. 920-33.
8. Adler CH, Dugger BN, Hentz JG, Hinni ML, Lott DG, Driver-Dunckley E, Mehta S, Serrano G, Sue LI, Duffy A, Intorcia A, Filon J, Pullen J, Walker DG, Beach TG. Peripheral synucleinopathy in early Parkinson's disease: submandibular gland Needle biopsy findings. Mov Disord. 2016;31(2):250-6. https://doi.org/10.1002/mds.26476 PMID: 26799362 PMCID: PMC4747813
9. Campo F, Carletti R, Fusconi M, Pellicano C, Pontieri FE, Di Gioia CR, Vincentiis M. Alpha-synuclein in salivary gland as biomarker for Parkinson's disease. Rev Neurosci. 2019;30(5):455-462. https://doi.org/10.1515/revneuro-2018-0064 PMID: 30471223
10. Sian J, Dexter DT, Lees AJ, Daniel S, Agid Y, Javoy-Agid F, Jenner P, Marsden CD. Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia. Ann Neurol. 1994;36(3):348-55. https://doi.org/10.1002/ana.410360305 PMid:8080242
11. Greenfield JG, Bosanquet FD. The brain-stem lesions in parkinsonism. J Neurol Neurosurg Psychiatry. 1953;16(4):213-26. https://doi.org/10.1136/jnnp.16.4.213 PMID: 13109537 PMCID: PMC503142
12. Zavariz RC, Limeira DM. Possíveis etiologias para a Doença de Parkinson: Uma breve revisão bibliográfica. Saúde Pesqui. 2012;5(2):388-98. https://periodicos.unicesumar.edu.br/index.php/saudpesq/article/view/1818
13. Da Silva Correia MDG, de Jesus AVF, Messias GMS, Nunes TLGM, Gomes MZ, da Paixão AO, Silva FS, Nunes TLGM, Santos TBG. Doença de Parkinson: uma desordem neurodegenerativa. Cad. Grad. Ciênc Biol Saúde Unit. 2013;1(2),57-65. https://periodicos.set.edu.br/cadernobiologicas/article/view/290
14. Tansey MG, Wallings RL, Houser MC, Herrick MK, Keating CE, Joers V. Inflammation and immune dysfunction in Parkinson disease. Nat Rev Immunol. 2022;22(11):657-73. https://doi.org/10.1038/s41577-022-00684-6 PMid:35246670 PMCid:PMC8895080
15. Souza CFM, Almeida HCP, Sousa JB, Costa PH, Silveira YSS, Bezerra JCL. A doença de Parkinson e o processo de envelhecimento motor: uma revisão de literatura. Rev Neurocienc. 2011;19(4):718-23. https://doi.org/10.34024/rnc.2011.v19.8330
16. Alves SCC. Fisiopatologia dos gânglios base na doença de Parkinson [master's thesis on internet]. Coimbra: Faculdade de Medicina da Universidade de Coimbra; 2012. https://hdl.handle.net/10316/84946
17. Jankovic J, Hallett M, Okun MS, Comella CL, Fahn S, Goldman J. Principles and practice of movement disorders. 3a ed. London: Elsevier Health Sciences; 2021. Chapter 26, Peripheral movement disorders; p. 585-90. https://doi.org/10.1016/B978-0-323-31071-0.00026-3
18. Barone P, Antonini A, Colosimo C, Marconi R, Morgante L, Avarello TP, Bottacchi E, Cannas A, Ceravolo G, Ceravolo R, Cicarelli G, Gaglio RM, Giglia RM, Iemolo F, Manfredi M, Meco G, Nicoletti A, Pederzoli M, Petrone A, Pisani A, Pontieri FE, Quatrale R, Ramat S, Scala R, Volpe G, Zappulla S, Bentivoglio AR, Stocchi F, Trianni G, Del Dotto P. The PRIAMO study: a multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease. Mov Disord. 2009;24(11):1641-9. https://doi.org/10.1002/mds.22643 PMid:19514014
19. O'Sullivan SS, Williams DR, Gallagher DA, Massey LA, Silveira-Moriyama L, Lees AJ. Nonmotor symptoms as presenting complaints in Parkinson's disease: a clinicopathological study. Mov Disord. 2008;23(1):101-6. https://doi.org/10.1002/mds.21813 PMid:17994582
20. Goetz CG, Tilley BC, Schaftman S. Clinimetric testing of the new UPDRS (MDS-UPDRS) vs original version. Movement Disorders. 2007;22 (Suppl. 16): S6.
21. Teive HAG. Etiopatogenia da doença de Parkinson. Rev Neurocienc. 2005;13:201-14. https://doi.org/10.34024/rnc.2005.v13.8794
22. Dickson DW, Braak H, Duda JE, Duyckaerts C, Gasser T, Halliday GM, Litvan I. Neuropathological assessment of Parkinson's disease: refining the diagnostic criteria. Lancet Neurol. 2009;8(12):1150-7. https://doi.org/10.1016/S1474-4422(09)70238-8 PMid:19909913
23. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging. 2003;24(2):197-211 https://doi.org/10.1016/S0197-4580(02)00065-9 PMid:12498954
24. Postuma RB, Berg D. Advances in markers of prodromal Parkinson disease. Nat Rev Neurol. 2016;12(11):622-34. https://doi.org/10.1038/nrneurol.2016.152 PMid:27786242
25. Braak H, Del TK. Invited article: nervous system pathology in sporadic Parkinson disease. Neurology. 2008;70(20):1916-25. https://doi.org/10.1212/01.wnl.0000312279.49272.9f PMid:18474848
26. Berg D, Postuma RB, Bloem B, Chan P, Dubois B, Gasser T, Goetz CG, Halliday GM, Hardy J, Lang AE, Litvan I, Marek K, Obeso J, Oertel W, Olanow CW, Poewe W, Stern M, Deuschl G. Time to redefine PD? Introductory statement of the MDS Task Force on the definition of Parkinson's disease. Mov Disord. 2014;29(4):454-62 https://doi.org/10.1002/mds.25844 PMid:24619848 PMCid:PMC4204150
27. Berg D, Postuma RB, Adler CH, Bloem BR, Chan P, Dubois B, Gasser T, Goetz CG, Halliday G, Joseph L, Lang AE, Liepelt-Scarfone I, Litvan I, Marek K, Obeso J, Oertel W, Olanow CW, Poewe W, Stern M, Deuschl G. MDS research criteria for prodromal Parkinson's disease. Mov Disord. 2015;30(12):1600-11. https://doi.org/10.1002/mds.26431 PMid:26474317
28. Heinzel S, Berg D, Gasser T, Chen H, Yao C, Postuma RB. Update of the MDS research criteria for prodromal Parkinson's disease. Mov Disord. 2019;34(10):1464-70. https://doi.org/10.1002/mds.27802 PMid:31412427
29.Starkstein SE, Brockman S. Management of depression in Parkinson's disease: a systematic review. Mov Disord Clin Pract. 2017;4:470-77. https://doi.org/10.1002/mdc3.12507 PMid:30363415 PMCid:PMC6174394
30. Ravina B, Camicioli R, Como PG, Marsh L, Jankovic J, Weintraub D, Elm J. The impact of depressive symptoms in early Parkinson disease. Neurology. 2007;69(4):342-7. https://doi.org/10.1212/01.wnl.0000268695.63392.10 PMid:17581943 PMCid:PMC2031220
31. Schrag A, Horsfall L, Walters K, Noyce A, Petersen I. Apresentações pré-diagnósticas da doença de Parkinson na atenção primária: um estudo caso-controle. Lancet Neurol. 2015;14(1):57-64. https://doi.org/10.1016/S1474-4422(14)70287-X PMid:25435387
32. Gaenslen A, Wurster I, Brockmann K, Huber H, Godau J, Faust B, Lerche S, Eschweiler GW, Maetzler W, Berg D. Prodromal features for Parkinson's disease--baseline data from the TREND study. Eur J Neurol. 2014;21(5):766-72. https://doi.org/10.1111/ene.12382 PMid:24612314
33. Ma J, Dou K, Liu R, Liao Y, Yuan Z, Xie A. Associations of Sleep Disorders With Depressive Symptoms in Early and Prodromal Parkinson's Disease. Front Aging Neurosci. 2022;14:898149. https://doi.org/10.3389/fnagi.2022.898149 PMid:35754965 PMCid:PMC9226450
34. Bohlken J, Schrag A, Riedel-Heller S, Kostev K. Identification of Prodromal Presentations of Parkinson's Disease among Primary Care Outpatients in Germany. Neuroepidemiology. 2022;56(1):41-9. https://doi.org/10.1159/000520574 PMid:34724667
35. Roos DS, Klein M, Deeg DJH, Doty RL, Berendse HW. Prevalence of Prodromal Symptoms of Parkinson's Disease in the Late Middle-Aged Population. J Parkinsons Dis. 2022;12(3):967-74. https://doi.org/10.3233/JPD-213007 PMid:35180132 PMCid:PMC9108586
36. Kazmi H, Walker Z, Booij J, Khan F, Shah S, Sudre CH, Buckman JEJ, Schrag AE. Late onset depression: dopaminergic deficit and clinical features of prodromal Parkinson's disease: a cross-sectional study. J Neurol Neurosurg Psychiatry. 2021;92(2):158-64. https://doi.org/10.1136/jnnp-2020-324266 PMid:33268471 PMCid:PMC7841491
37. Gustafsson H, Nordström A, Nordström P. Depression and subsequent risk of Parkinson disease: A nationwide cohort study. Neurology. 2015;84(24):2422-9. https://doi.org/10.1212/WNL.0000000000001684 PMid:25995056 PMCid:PMC4478031
38. Hinkle JT, Perepezko K, Gonzalez LL, Mills KA, Pontone GM. Apathy and Anxiety in De Novo Parkinson's Disease Predict the Severity of Motor Complications. Mov Disord Clin Pract. 2020;8(1):76-84. https://doi.org/10.1002/mdc3.13117 PMid:33426161 PMCid:PMC7780944
39. Liu JB, Leng JL, Zhang XJ, Wang ZX, Duan ZW, Mao CJ, Liu CF. Investigation of non-motor symptoms in first-degree relatives of patients with Parkinson's disease. Parkinsonism Relat Disord. 2018;52:62-8. https://doi.org/10.1016/j.parkreldis.2018.03.021 PMid:29606605
40. Leentjens AF, Van den Akker M, Metsemakers JF, Lousberg R, Verhey FR. Higher incidence of depression preceding the onset of Parkinson's disease: a register study. Mov Disord. 2003;18(4):414-8. https://doi.org/10.1002/mds.10387 PMid:12671948
41. Heinzel S, Berg D, Gasser T, Chen H, Yao C, Postuma RB. Update of the MDS research criteria for prodromal Parkinson's disease. Mov Disord. 2019;34(10):1464-70. https://doi.org/10.1002/mds.27802 PMid:31412427
42. Walter U, Heilmann R, Kaulitz L, Just T, Krause BJ, Benecke R, Höppner J. Prediction of Parkinson's disease subsequent to severe depression: a ten-year follow-up study. J Neural Transm (Viena). 2015;122(6):789-97. https://doi.org/10.1007/s00702-014-1313-0 PMid:25217967
43. Karlsen KH, Larsen JP, Tandberg E, Maeland JG. Influence of clinical and demographic variables on quality of life in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry. 1999;66(4):431-5. https://doi.org/10.1136/jnnp.66.4.431 PMid:10201412 PMCid:PMC1736304
44. Kirsch-Darrow L, Fernandez HH, Marsiske M, Okun MS, Bowers D. Dissociating apathy and depression in Parkinson disease. Neurology. 2006;67(1):33-8. https://doi.org/10.1212/01.wnl.0000230572.07791.22 PMid:16832074 PMCid:PMC2911155
45. Dujardin K, Sockeel P, Delliaux M, Destée A, Defebvre L. Apathy may herald cognitive decline and dementia in Parkinson's disease. Mov Disord. 2009;24(16):2391-7. https://doi.org/10.1002/mds.22843 PMid:19908317
46. Barone D. A., Henchcliffe C. Rapid eye movement sleep behavior disorder and the link to alpha-synucleinopathies. Clin Neurophysiol. 2018;129(8):1551-64. https://doi.org/10.1016/j.clinph.2018.05.003 PMid:29883833 PMCid:PMC6495539
47. Orayj K, Almeleebia T, Vigneshwaran E, Alshahrani S, Alavudeen SS, Alghamdi W. Trend of recognizing depression symptoms and antidepressants use in newly diagnosed Parkinson's disease: Population-based study. Brain Behav. 2021;11(8):e2228. https://doi.org/10.1002/brb3.2228 PMid:34124851 PMCid:PMC8413829
48. Nissenbaum H, Quinn NP, Brown RG, Toone B, Gotham AM, Marsden CD. Mood swings associated with the 'on-off' phenomenon in Parkinson's disease. Psychol Med. 1987;17(4):899-904. https://doi.org/10.1017/S0033291700000702 PMid:3432464
49. Postuma RB, Gagnon J-F, Bertrand J-A, Genier Marchand D, Montplaisir JY. Parkinson risk in idiopathic REM sleep behavior disorder: preparing for neuroprotective trials. Neurology 2015;84:1104-1113. https://doi.org/10.1212/WNL.0000000000001364 PMid:25681454 PMCid:PMC4371408
50. Mahlknecht P, Iranzo A, Hogl B, Frauscher B, Müller C, Santamaría J, Tolosa E, Serradell M, Mitterling T, Gschliesser V, Goebel G, Brugger F, Scherfler C, Poewe W, Seppi K. Olfactory dysfunction predicts early transition to a Lewy body disease in idiopathic RBD. Neurology. 2015;84(7):654-8. https://doi.org/10.1212/WNL.0000000000001265 PMid:25609758
51. Berg D, Postuma RB, Adler CH, Bloem BR, Chan P, Dubois B, Gasser T, Goetz CG, Halliday G, Joseph L, Lang AE, Liepelt-Scarfone I, Litvan I, Marek K, Obeso J, Oertel W, Olanow CW, Poewe W, Stern M, Deuschl G. MDS research criteria for prodromal Parkinson's disease. Mov Disord. 2015;30(12):1600-11. https://doi.org/10.1002/mds.26431 PMid:26474317
52. Bareeqa SB, Samar SS, Kamal S, Masood Y, Allahyar Ahmed SI, Hayat G. Prodromal depression and subsequent risk of developing Parkinson's disease: a systematic review with meta-analysis. Neurodegener Dis Manag. 2022;12(3):155-64. https://doi.org/10.2217/nmt-2022-0001 PMid:35512296
53. Lee T, Lee HB, Ahn MH, Kim J, Kim MS, Chung SJ, Hong JP. Increased suicide risk and clinical correlates of suicide among patients with Parkinson's disease. Parkinsonism Relat Disord. 2016;32:102-07. https://doi.org/10.1016/j.parkreldis.2016.09.006 PMid:27637284
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