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Longitudinal medication profile and cost savings in Parkinson’s disease patients after bilateral subthalamic nucleus deep brain stimulation



Deep brain stimulation of the subthalamic nucleus (STN DBS) has been shown to reduce antiparkinsonian medication in Parkinson’s disease. We aimed to investigate the changes in long-term medication profile with STN DBS.


Antiparkinsonian medication data for 56 patients were collected from as early as 3 years before STN DBS up to 10 years after. Cost spending on medication changes was analyzed. Mean levodopa equivalent daily dose (LEDD) was projected 10 years into the future based on preoperative data to create a comparator group wherein the patients did not undergo STN DBS. Use of neuroleptics and antidepressants was also recorded.


LEDD requirement was significantly reduced by a mean of 31 ± 2% over 10 years after DBS, from 1049 ± 381 mg at pre-DBS baseline, to 713 ± 392 mg at 1 year post-DBS, and 712 ± 385 mg at 10 years post-DBS. This was associated with a mean reduction of 35 ± 3% in medicine cost. Modeled LEDD requirements for not having STN DBS were in the range of 1489 mg to 2721 mg at 10 years post-DBS (109–282% higher than the observed mean LEDD in DBS cohort). The proportion of patients increased from 5% before STN DBS to 14% at 10 year post-DBS for neuroleptics, and 11–23% for antidepressants.


STN DBS led to LEDD reduction and antiparkinsonian medication cost savings in our South-East Asian cohort. Medication reduction with STN DBS in our cohort over the 10-year period was comparable to those reported in Western populations.

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  1. 1.

    Williams A, Gill S, Varma T, Jenkinson C, Quinn N, Mitchell R, Scott R, Ives N, Rick C, Daniels J, Patel S, Wheatley K (2010) Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson’s disease (PD SURG trial): a randomised, open-label trial. Lancet Neurol 9:581–591.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schafer H, Botzel K, Daniels C, Deutschländer A, Dillmann U, Eisner W, Gruber D, Hamel W, Herzog J, Hilker R, Klebe S, Kloss M, Koy J, Krause M, Kupsch A, Lorenz D, Lorenzl S, Mehdorn HM, Moringlane JR, Oertel W, Pinsker MO, Reichmann H, Reuss A, Schneider GH, Schnitzler A, Steude U, Sturm V, Timmermann L, Tronnier V, Trottenberg T, Wojtecki L, Wolf E, Poewe W, Voges J (2006) A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med 355:896–908.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Schuepbach WM, Rau J, Knudsen K, Volkmann J, Krack P, Timmermann L, Hälbig TD, Hesekamp H, Navarro SM, Meier N, Falk D, Mehdorn M, Paschen S, Maarouf M, Barbe MT, Fink GR, Kupsch A, Gruber D, Schneider GH, Seigneuret E, Kistner A, Chaynes P, Ory-Magne F, Brefel Courbon C, Vesper J, Schnitzler A, Wojtecki L, Houeto JL, Bataille B, Maltête D, Damier P, Raoul S, Sixel-Doering F, Hellwig D, Gharabaghi A, Krüger R, Pinsker MO, Amtage F, Régis JM, Witjas T, Thobois S, Mertens P, Kloss M, Hartmann A, Oertel WH, Post B, Speelman H, Agid Y, Schade-Brittinger C, Deuschl G (2013) Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med 368:610–622.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Weaver FM, Stroupe KT, Cao L, Holloway RG, Vickrey BG, Simuni T, Hendricks A, Ippolito D (2012) Parkinson's disease medication use and costs following deep brain stimulation. Mov Disord 27:1398–1403.

    Article  PubMed  Google Scholar 

  5. 5.

    Kleiner-Fisman G, Herzog J, Fisman DN, Tamma F, Lyons KE, Pahwa R, Lang AE, Deuschl G (2006) Subthalamic nucleus deep brain stimulation: summary and meta-analysis of outcomes. Mov Disord 21:S290–S304.

    Article  PubMed  Google Scholar 

  6. 6.

    Romito LM, Albanese A (2010) Dopaminergic therapy and subthalamic stimulation in Parkinson’s disease: a review of 5-year reports. J Neurol 257:298–304.

    CAS  Article  Google Scholar 

  7. 7.

    Fasano A, Romito LM, Daniele A, Piano C, Zinno M, Bentivoglio AR, Albanese A (2010) Motor and cognitive outcome in patients with Parkinson’s disease 8 years after subthalamic implants. Brain 133:2664–2676.

    Article  PubMed  Google Scholar 

  8. 8.

    Merola A, Zibetti M, Angrisano S, Rizzi L, Ricchi V, Artusi CA, Lanotte M, Rizzone MG, Lopiano L (2011) Parkinson’s disease progression at 30 years: a study of subthalamic deep brain-stimulated patients. Brain 134:2074–2084.

    Article  PubMed  Google Scholar 

  9. 9.

    Aviles-Olmos I, Kefalopoulou Z, Tripoliti E, Candelario J, Akram H, Martinez-Torres I, Jahanshahi M, Foltynie T, Hariz M, Zrinzo L, Limousin P (2014) Long-term outcome of subthalamic nucleus deep brain stimulation for Parkinson's disease using an MRI-guided and MRI-verified approach. J Neurol Neurosurg Psychiatry 85:1419–1425.

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Zibetti M, Merola A, Rizzi L, Ricchi V, Angrisano S, Azzaro C, Artusi CA, Arduino N, Marchisio A, Lanotte M, Rizzone M, Lopiano L (2011) Beyond nine years of continuous subthalamic nucleus deep brain stimulation in Parkinson's disease. Mov Disord 26:2327–2334.

    Article  PubMed  Google Scholar 

  11. 11.

    Castrioto A, Lozano AM, Poon YY, Lang AE, Fallis M, Moro E (2011) Ten-year outcome of subthalamic stimulation in Parkinson disease: a blinded evaluation. Arch Neurol 68:1550–1556.

    Article  PubMed  Google Scholar 

  12. 12.

    Rizzone MG, Fasano A, Daniele A, Zibetti M, Merola A, Rizzi L, Piano C, Piccininni C, Romito LM, Lopiano L, Albanese A (2014) Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: from the advanced phase towards the late stage of the disease? Parkinsonism Relat Disord 20:376–381.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Janssen ML, Duits AA, Turaihi AH, Ackermans L, Leentjens AF, Leentjes AF, van Kranen-Mastenbroek V, Oosterloo M, Visser-Vandewalle V, Temel Y (2014) Subthalamic nucleus high-frequency stimulation for advanced Parkinson's disease: motor and neuropsychological outcome after 10 years. Stereotac Funct Neurosurg 92:381–387.

    Article  Google Scholar 

  14. 14.

    Bang Henriksen M, Johnsen EL, Sunde N, Vase A, Gjelstrup MC, Østergaard K (2016) Surviving 10 years with deep brain stimulation for Parkinson's disease–a follow-up of 79 patients. Eur J Neurol 23:53–61.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Krishnan S, Prasad S, Pisharady KK, Sarma G, Sarma SP, Kishore A (2016) The decade after subthalamic stimulation in advanced Parkinson's disease: a balancing act. Neurol India 64:81–89.

    Article  PubMed  Google Scholar 

  16. 16.

    Alexoudi A, Shalash A, Knudsen K, Witt K, Mehdorn M, Volkmann J, Deuschl G (2015) The medical treatment of patients with Parkinson's disease receiving subthalamic neurostimulation. Parkinsonism Relat Disord 21:555–560.

    Article  PubMed  Google Scholar 

  17. 17.

    Krack P, Batir A, Van Blercom N, Chabardes S, Fraix V, Ardouin C, Koudsie A, Limousin PD, Benazzouz A, LeBas JF, Benabid AL, Pollak P (2003) Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson's disease. N Engl J Med 349:1925–1934.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Wider C, Pollo C, Bloch J, Burkhard PR, Vingerhoets FJ (2008) Long-term outcome of 50 consecutive Parkinson's disease patients treated with subthalamic deep brain stimulation. Parkinsonism Relat Disord 14:114–119.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Schüpbach WM, Chastan N, Welter ML, Houeto JL, Mesnage V, Bonnet AM, Czernecki V, Maltete D, Hartmann A, Mallet L, Pidoux B, Dormont D, Navarro S, Cornu P, Mallet A, Agid Y (2005) Stimulation of the subthalamic nucleus in Parkinson’s disease: a 5 year follow up. J Neurol Neurosurg Psychiatry 76:1640–1644.

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Merola A, Rizzi L, Zibetti M, Artusi CA, Montanaro E, Angrisano S, Lanotte M, Rizzone MG, Lopiano L (2014) Medical therapy and subthalamic deep brain stimulation in advanced Parkinson's disease: a different long-term outcome? J Neurol Neurosurg Psychiatry 85:552–559.

    Article  PubMed  Google Scholar 

  21. 21.

    Gervais-Bernard H, Xie-Brustolin J, Mertens P, Polo G, Klinger H, Adamec D, Broussolle E, Thobois S (2009) Bilateral subthalamic nucleus stimulation in advanced Parkinson’s disease: five year follow-up. J Neurol 256:225–233.

    Article  PubMed  Google Scholar 

  22. 22.

    Piboolnurak P, Lang AE, Lozano AM, Miyasaki JM, Saint-Cyr JA, Poon YY, Hutchison WD, Dostrovsky JO, Moro E (2007) Levodopa response in long-term bilateral subthalamic stimulation for Parkinson's disease. Mov Disord 22:990–997.

    Article  PubMed  Google Scholar 

  23. 23.

    Romito LM, Contarino MF, Vanacore N, Bentivoglio AR, Scerrati M, Albanese A (2009) Replacement of dopaminergic medication with subthalamic nucleus stimulation in Parkinson's disease: long-term observation. Mov Disord 24:557–563.

    Article  PubMed  Google Scholar 

  24. 24.

    Simonin C, Tir M, Devos D, Kreisler A, Dujardin K, Salleron J, Delval A, Blond S, Defebvre L, Destee A, Krystkowiak P (2009) Reduced levodopa-induced complications after 5 years of subthalamic stimulation in Parkinson’s disease: a second honeymoon. J Neurol 256:1736–1741.

    Article  PubMed  Google Scholar 

  25. 25.

    Moro E, Lozano AM, Pollak P, Agid Y, Rehncrona S, Volkmann J, Kulisevsky J, Obeso JA, Albanese A, Hariz MI, Quinn NP, Speelman JD, Benabid AL, Fraix V, Mendes A, Welter ML, Houeto JL, Cornu P, Dormont D, Tornqvist AL, Ekberg R, Schnitzler A, Timmermann L, Wojtecki L, Gironell A, Rodriguez-Oroz MC, Guridi J, Bentivoglio AR, Contarino MF, Romito L, Scerrati M, Janssens M, Lang AE (2010) Long-term results of a multicenter study on subthalamic and pallidal stimulation in Parkinson's disease. Mov Disord 25:578–586.

    Article  PubMed  Google Scholar 

  26. 26.

    Li J, Zhang Y, Li Y (2015) Long-term follow-up of bilateral subthalamic nucleus stimulation in Chinese Parkinson's disease patients. Br J Neurosurg 29:329–333.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Lilleeng B, Gjerstad M, Baardsen R, Dalen I, Larsen JP (2015) Motor symptoms after deep brain stimulation of the subthalamic nucleus. Acta Neurol Scand 131:298–304.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Charles PD, Padaliya BB, Newman WJ, Gill CE, Covington CD, Fang JY, So SA, Tramontana MG, Konrad PE, Davis TL (2004) Deep brain stimulation of the subthalamic nucleus reduces antiparkinsonian medication costs. Parkinsonism Relat Disord 10:475–479.

    Article  PubMed  Google Scholar 

  29. 29.

    Hacker ML, Currie AD, Molinari AL, Turchan M, Millan SM, Heusinkveld LE, Roach J, Konrad PE, Davis TL, Neimat JS, Phibbs FT, Hedera P, Byrne DW, Charles D (2016) Subthalamic nucleus deep brain stimulation may reduce medication costs in early stage Parkinson’s disease. J Parkinsons Dis 6:125–131.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Toft M, Dietrichs E (2014) Medication costs following subthalamic nucleus deep brain stimulation for Parkinson's disease. Mov Disord 29:275–276.

    Article  PubMed  Google Scholar 

  31. 31.

    Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE (2010) Systematic review of levodopa dose equivalency reporting in Parkinson's disease. Mov Disord 25:2649–2653.

    Article  PubMed  Google Scholar 

  33. 33.

    Holt CC (2004) Forecasting seasonals and trends by exponentially weighted moving averages. Int J Forecast 20:5–10.

    Article  Google Scholar 

  34. 34.

    Mamdani M, Rapoport M, Shulman KI, Herrmann N, Rochon PA (2005) Mental health-related drug utilization among older adults: prevalence, trends, and costs. Am J Geriatr Psychiatry 13:892–900.

    Article  PubMed  Google Scholar 

  35. 35.

    Vasudev A, Shariff SZ, Liu K, Burhan AM, Herrmann N, Leonard S, Mamdani M (2015) Trends in psychotropic dispensing among older adults with dementia living in long-term care facilities: 2004–2013. Am J Geriatr Psychiatry 23:1259–1269.

    Article  PubMed  Google Scholar 

  36. 36.

    Bonnet AM, Loria Y, Saint-Hilaire MH, Lhermitte F, Agid Y (1987) Does long-term aggravation of Parkinson’s disease result from nondopaminergic lesions? Neurology 37:1539–1542.

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17:427–442.

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Schrag A, Dodel R, Spottke A, Bornschein B, Siebert U, Quinn NP (2007) Rate of clinical progression in Parkinson’s disease. A prospective study. Mov Disord 22:938–945.

    Article  PubMed  Google Scholar 

  39. 39.

    Tagliati M, Martin C, Alterman R (2010) Lack of motor symptoms progression in Parkinson's disease patients with long-term bilateral subthalamic deep brain stimulation. Int J Neurosci 120:717–723.

    Article  PubMed  Google Scholar 

  40. 40.

    Gardner ES, McKenzie E (1985) Forecasting trends in time series. Manag Sci 31:1237–1246.

    Article  Google Scholar 

  41. 41.

    R Foundation for Statistical Computing, Vienna, Austria, 2017.

  42. 42.

    Hyndman RJ, Athanasopoulos G (2017) Forecasting: principles and practice. OTexts, Melbourne, Australia

    Google Scholar 

  43. 43.

    Wickham H (2009) ggplot2: elegant graphics for data analysis. Springer-Verlag, New York

    Book  Google Scholar 

  44. 44.

    GBD 2016 Causes of Death Collaborators (2017) Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 390:1151–1210.

    Article  Google Scholar 

  45. 45.

    Foreman KJ, Marquez N, Dolgert A, Fukutaki K, Fullman N, McGaughey M, Pletcher MA, Smith AE, Tang K, Yuan CW, Brown JC, Friedman J, He J, Heuton KR, Holmberg M, Patel DJ, Reidy P, Carter A, Cercy K, Chapin A, Douwes-Schultz D, Frank T, Goettsch F, Liu PY, Nandakumar V, Reitsma MB, Reuter V, Sadat N, Sorensen RJD, Srinivasan V, Updike RL, York H, Lopez AD, Lozano R, Lim SS, Mokdad AH, Vollset SE, Murray CJL (2018) Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016–40 for 195 countries and territories. Lancet 392:2052–2090.

    Article  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Rodriguez-Oroz MC, Moro E, Krack P (2012) Long-term outcomes of surgical therapies for Parkinson’s disease. Mov Disord 27:1718–1728.

    Article  PubMed  Google Scholar 

  47. 47.

    Moro E, Esselink RJ, Benabid AL, Pollak P (2002) Response to levodopa in parkinsonian patients with bilateral subthalamic nucleus stimulation. Brain 125:2408–2417.

    Article  PubMed  Google Scholar 

  48. 48.

    Fasano A, Aquino CC, Krauss JK, Honey CR, Bloem BR (2015) Axial disability and deep brain stimulation in patients with Parkinson disease. Nat Rev Neurol 11:98–110.

    Article  PubMed  Google Scholar 

  49. 49.

    McColl CD, Reardon KA, Shiff M, Kempster PA (2002) Motor response to levodopa and the evolution of motor fluctuations in the first decade of treatment of Parkinson’s disease. Mov Disord 17:1227–1234.

    Article  PubMed  Google Scholar 

  50. 50.

    Goetz CG, Stebbins GT, Blasucci LM (2000) Differential progression of motor impairment in levodopa-treated Parkinson’s disease. Mov Disord 15:479–484

    CAS  Article  Google Scholar 

  51. 51.

    Reardon KA, Shiff M, Kempster PA (1999) Evolution of motor fluctuations in Parkinson’s disease: a longitudinal study over 6 years. Mov Disord 14:605–611

    CAS  Article  Google Scholar 

  52. 52.

    Rascol O, Payoux P, Ory F, Ferreira JJ, Brefel-Courbon C, Montastruc JL (2003) Limitations of current Parkinson’s disease therapy. Ann Neurol 53:S3–S15.

    CAS  Article  Google Scholar 

  53. 53.

    Zibetti M, Pesare M, Cinquepalmi A, Rosso M, Bergamasco B, Ducati A, Lanotte M, Lopiano L (2008) Antiparkinsonian therapy modifications in PD patients after STN DBS: a retrospective observational analysis. Parkinsonism Relat Disord 14:608–612.

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Zibetti M, Cinquepalmi A, Angrisano S, Lanotte M, Lopiano L (2009) Management of antiparkinsonian therapy during chronic subthalamic stimulation in Parkinson's disease. Parkinsonism Relat Disord 15:S76–S80.

    Article  PubMed  Google Scholar 

  55. 55.

    Findley LJ, Wood E, Lowin J, Roeder C, Bergman A, Schifflers M (2011) The economic burden of advanced Parkinson’s disease: an analysis of a UK patient dataset. J Med Econ 14:130–139.

    Article  PubMed  Google Scholar 

  56. 56.

    Couto MI, Monteiro A, Oliveira A, Lunet N, Massano J (2014) Depression and anxiety following deep brain stimulation in Parkinson’s disease: systematic review and meta-analysis. Acta Med Port 27:372–382

    Article  Google Scholar 

  57. 57.

    Hely MA, Reid WG, Adena MA, Halliday GM, Morris JG (2008) The Sydney multicenter study of Parkinson's disease: the inevitability of dementia at 20 years. Mov Disord 23:837–844.

    Article  PubMed  Google Scholar 

  58. 58.

    Lhommée E, Wojtecki L, Czernecki V, Witt K, Maier F, Tonder L, Timmermann L, Hälbig TD, Pineau F, Durif F, Witjas T, Pinsker M, Mehdorn M, Sixel-Döring F, Kupsch A, Krüger R, Elben S, Chabardès S, Thobois S, Brefel-Courbon C, Ory-Magne F, Regis JM, Maltête D, Sauvaget A, Rau J, Schnitzler A, Schüpbach M, Schade-Brittinger C, Deuschl G, Houeto JL, Krack P (2018) Behavioural outcomes of subthalamic stimulation and medical therapy versus medical therapy alone for Parkinson's disease with early motor complications (EARLYSTIM trial): secondary analysis of an open-label randomised trial. Lancet Neurol 17:223–231.

    Article  PubMed  Google Scholar 

  59. 59.

    Lawrence AD, Evans AH, Lees AJ (2003) Compulsive use of dopamine replacement therapy in Parkinson's disease: reward systems gone awry? Lancet Neurol 2:595–604

    CAS  Article  Google Scholar 

  60. 60.

    Voon V, Fernagut PO, Wickens J, Baunez C, Rodriguez M, Pavon N, Juncos JL, Obeso JA, Bezard E (2009) Chronic dopaminergic stimulation in Parkinson's disease: from dyskinesias to impulse control disorders. Lancet Neurol 8:1140–1149.

    CAS  Article  PubMed  Google Scholar 

  61. 61.

    Weintraub D, Koester J, Potenza MN, Siderowf AD, Stacy M, Voon V, Whetteckey J, Wunderlich GR, Lang AE (2010) Impulse control disorders in Parkinson disease: a cross-sectional study of 3090 patients. Arch Neurol 67:589–595.

    Article  PubMed  Google Scholar 

  62. 62.

    Lhommée E, Klinger H, Thobois S, Schmitt E, Ardouin C, Bichon A, Kistner A, Fraix V, Xie J, Aya Kombo M, Chabardès S, Seigneuret E, Benabid AL, Mertens P, Polo G, Carnicella S, Quesada JL, Bosson JL, Broussolle E, Pollak P, Krack P (2012) Subthalamic stimulation in Parkinson’s disease: restoring the balance of motivated behaviours. Brain 135:1463–1477.

    Article  PubMed  Google Scholar 

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This research was supported by the Singapore Ministry of Health’s National Medical Research Council research grants (NMRC/CNIG/1173/2017 and TCMRG/NNI310301).

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AS and NK were responsible for the conception and design of the study. JN and AS were responsible for data collection. JN, AS, and NK were responsible for data analyses. JN, AS, ZX, and NK contributed to the interpretation of the data. JN and AS drafted the article, which was critically revised by all authors. All authors have approved the final version of the manuscript.

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Correspondence to Nicolas Kon Kam King.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

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This retrospective review was carried out with waiver of consent by the SingHealth Centralized Institutional Review Board.

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Ng, J.H., See, A.A.Q., Xu, Z. et al. Longitudinal medication profile and cost savings in Parkinson’s disease patients after bilateral subthalamic nucleus deep brain stimulation. J Neurol 267, 2443–2454 (2020).

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  • Antiparkinsonian medication
  • Subthalamic nucleus
  • Deep brain stimulation
  • Long term
  • Parkinson’s disease
  • Asian
  • Cost analysis