한국임상약학회지 (Korean Journal of Clinical Pharmacy)

  • 제28권4호
  • /
  • Pages.285-292
  • /
  • 2018
  • /
  • 1226-6051(pISSN)
  • /
  • 2508-786X(eISSN)
한국임상약학회 (Korean College Of Clinical Pharmacy)
권호 표지
DOI QR코드

DOI QR Code

레보도파 요법 중인 파킨슨병 환자의 인지장애 위험 인자 연구

Risk Factors for Cognitive Impairment in Patient with Parkinson's Disease Treated with Levodopa

  • Kim, Kyung Sook (Department of Clinical Pharmacy, Chungbuk National University Hospital) ;
  • Lee, Kyung Eun (Department of Pharmacy, College of Pharmacy, Chungbuk National University) ;
  • Lee, Myung Koo (Department of Pharmacy, College of Pharmacy, Chungbuk National University)
  • 투고 : 2018.07.27
  • 심사 : 2018.10.29
  • 발행 : 2018.12.29
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Background: Long-term levodopa therapy relieves the motor dysfunction associated with Parkinson's disease (PD), but has various effects on non-motor symptoms, including cognitive dysfunction, hallucinations, and affective disorders, and can exacerbate certain aspects of dementia-like cognitive dysfunction. Here, we investigated the relationship between levodopa treatment and development of dementia in patients with PD. Methods: This retrospective study analyzed 76 consecutive patients with PD who had taken levodopa between 2011 and 2015. The participants were initially free of dementia and had initial daily levodopa doses of below 600 mg. Patients who did and did not develop comorbid dementia were compared in terms of potential predictor variables, including PD onset age, sex, levodopa doses, and non-dementia comorbidities. Results: Of the 76 patients, 21 (27.6%) developed dementia, which was followed by hallucinations and insomnia. The independent predictors of incident dementia were PD onset age and second-year and third-year average levodopa doses that were higher than the first-year average levodopa dose. Patients who developed dementia had significantly higher average daily levodopa doses and levodopa dose increases over the 6-year treatment period than those who did not develop dementia. In addition, patients with higher levodopa doses were more likely to experience hallucinations. Conclusion: These results suggest that increases in levodopa doses may be associated with a greater risk of cognitive impairment in patients with PD. Therefore, motor and cognitive functions and levodopa dose increases should be evaluated regularly during long-term levodopa therapy in patients with PD.

키워드

참고문헌

  1. Fahn S. Description of Parkinson's disease as a clinical syndrome. Ann N Y Acad Sci 2003; 991: 1-14.
  2. Williams-Gray CH, Foltynie T, Brayne CE, et al. Evolution of cognitive dysfunction in an incident Parkinson's disease cohort. Brain 2007; 130: 1787-98. https://doi.org/10.1093/brain/awm111
  3. Aarsland D, Andersen K, Larsen JP, et al. Risk of dementia in Parkinson's disease: a community-based, prospective study. Neurology 2001; 56: 730-6. https://doi.org/10.1212/WNL.56.6.730
  4. Cheng N, Maeda T, Kume T, et al. Differential neurotoxicity induced by L-DOPA and dopamine in cultured striatal neurons. Brain Res 1996; 743: 278-83. https://doi.org/10.1016/S0006-8993(96)01056-6
  5. Bianchine JR. Drug therapy of parkinsonism. N Engl J Med 1976; 295: 814-8. https://doi.org/10.1056/NEJM197610072951505
  6. Ludin HP, Bass-Verrey F. Study of deterioration in long-term treatment of parkinsonism with L-dopa plus decarboxylase inhibitor. J Neural Transm 1976; 38: 249-58. https://doi.org/10.1007/BF01249442
  7. Marsden CD, Parkes JD. "On-off" effects in patients with Parkinson's disease on chronic levodopa therapy. Lancet 1976; 1: 292-6.
  8. Marttila RJ. Diagnosis and epidemiology of Parkinson's disease. Acta Neurol Scand Suppl 1983; 95: 9-17.
  9. Cunha CD, Angelucci MEM, Canteras NS, et al. The lesion of the rat substantianigra pars compacta dopaminergic neurons as a model for Parkinson's disease memory disabilities. Cell Mol Neurobiol 2002; 22: 227-37. https://doi.org/10.1023/A:1020736131907
  10. Cools R, Stefanova E, Barker RA, et al. Dopaminergic modulation of high-level cognition in Parkinson's disease: the role of the prefrontal cortex revealed by PET. Brain 2002; 125: 584-94. https://doi.org/10.1093/brain/awf052
  11. Cheng N, Maeda T, Kume T, et al. Differential neurotoxicity induced by L-DOPA and dopamine in cultured striatal neurons. Brain Res 1996; 743: 278-83. https://doi.org/10.1016/S0006-8993(96)01056-6
  12. Jin CM, Yang YJ, Huang HS, et al. Induction of dopamine biosynthesis by l-DOPA in PC12 cells: implications of L-DOPA influx and cyclic AMP. Eur J Pharmacol 2008; 591: 88-95. https://doi.org/10.1016/j.ejphar.2008.06.052
  13. Murphy DL, Henry GM, Weingartner H. Catecholamines and Memory: Enhanced verbal learning during L-DOPA administration. Psychopharmacologia 1972; 27: 319-26. https://doi.org/10.1007/BF00429385
  14. Cools R, Stefanova E, Barker RA, et al. Dopaminergic modulation of high-level cognition in Parkinson's disease: The role of the prefrontal cortex revealed by PET. Brain 2002: 125: 584-94. https://doi.org/10.1093/brain/awf052
  15. Kostrzewa RM, Kostrzewa JP, Brus R. Neuroprotective and neurotoxic roles of levodopa (L-DOPA) in neurodegenerative disorders relating to Parkinson's disease. Amino Acids. 2002; 23(1-3):57-63. https://doi.org/10.1007/s00726-001-0110-x
  16. Lacy CF, Amstrong LL, Goldman MP, et al. (2009-2010) Drug information handbook 18th ed : Lexi-Comp Inc.
  17. Shulman LM, Taback RL, Bean J, et al. Comorbidity of the nonmotor symptoms of Parkinson's disease. Mov Disord 2001; 16: 507-10. https://doi.org/10.1002/mds.1099
  18. Aarsland D, Bronnick K, Ehrt U, et al. Neuropsychiatric symptoms in patients with Parkinson's disease and dementia: frequency, profile and associated care giver stress. J Neurol Neurosurg Psychiatry 2007; 78: 36-42. https://doi.org/10.1136/jnnp.2005.083113
  19. Han IT, Ha CK, Hong CG, et al. Behavioral and psychological symptoms in patients with Parkinson's disease according to cognitive function. Dementia and Neurocognitive Disorders 2012; 11: 104-10. https://doi.org/10.12779/dnd.2012.11.3.104
  20. Kim JW, Cheon SM, Park MJ, et al. Cognitive impairment in Parkinson's disease without dementia: subtypes and influences of age. J Clin Neurol 2009; 5: 133-8. https://doi.org/10.3988/jcn.2009.5.3.133
  21. Emre M, Aarsland D, Brown R, et al. Clinical diagnostic criteria for dementia associated with Parkinson's disease. Mov Disord 2007; 22: 1689-707. https://doi.org/10.1002/mds.21507
  22. Anang JB, Gagnon JF, Bertrand JA, et al. Predictors of dementia in Parkinson disease: a prospective cohort study. Neurology 2014; 83: 1253-60. https://doi.org/10.1212/WNL.0000000000000842
  23. Wang Q, Zhang Z, Li L, Wen H, et al. Assessment of cognitive impairment in patients with Parkinson's disease: prevalence and risk factors. Clin Interv Aging 2014; 9: 275-81.
  24. Rosdinom R, Fazli A, Ruzyanei NJ, et al. Factors associated with cognitive impairment in patients with Parkinson disease: an urban study. Clin Ter 2011; 162: 23-9.
  25. Hietanen M, Teravainen H. Dementia and treatment with L-dopa in Parkinson's disease. Mov Disord 1988; 3: 263-70. https://doi.org/10.1002/mds.870030311
  26. Hughes TA, Ross HF, Musa S, et al. A 10-year study of the incidence of and factors predicting dementia in Parkinson's disease. Neurology 2000; 54: 1596-602. https://doi.org/10.1212/WNL.54.8.1596
  27. Aarsland D, Andersen K, Larsen JP, et al. Risk of dementia in Parkinson's disease: a community-based, prospective study. Neurology 2001; 56: 730-6. https://doi.org/10.1212/WNL.56.6.730
  28. Zhu K, van Hilten JJ, Marinus J. Predictors of dementia in Parkinson's disease; findings from a 5-year prospective study using the SCOPACOG. Parkinsonism Relat Disord 2014; 20: 980-5. https://doi.org/10.1016/j.parkreldis.2014.06.006