Research Article
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The Mediating Effect of Caudate Nucleus Dopaminergic Activity on the Relationship Between Age and Cognitive Functions in Parkinson’s Disease Patients

Year 2024, Volume: 77 Issue: 4, 367 - 373, 31.12.2024

Abstract

Objectives: Advancing age is the primary risk factor for Parkinson’s disease (PD). In PD patients, dopaminergic activity is impaired, and cognitive dysfunctions are observed. This study investigated the mediating effect of caudate nucleus dopamine transporter binding score on the relationship between age and cognition in PD patients.

Materials and Methods: The open database of the Michael J. Fox Association was used, and data on 1,099 PD patients were accessed. Cognitive function scores and single-photon emission tomography findings assessing caudate nucleus dopaminergic activity were used.

Results: The caudate nucleus dopamine transporter binding score mediated the relationship between age and attention, processing speed, linguistic function, working memory, verbal episodic memory, and visual-spatial functions.

Conclusion: The cumulative neurodegenerative effect of age and PD requires monitoring of cognitive function. This study emphasizes the significance of considering dopaminergic activity in the caudate nucleus for diagnosing, monitoring, and treating cognitive functions in Parkinson’s disease.

Ethical Statement

The PPMI protocol was reviewed and approved by the Institutional Review Board and the Independent Ethics Committee (IRB/IEC) at each center and the study followed the Guideline for Good Clinical Practice. This study obtained the right to use the PPMI database data

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Thanks

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References

  • 1. GBD 2016 Parkinson’s Disease Collaborators. Global, regional, and national burden of Parkinson’s disease, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17:939-953.
  • 2. Leite Silva ABR, Gonçalves de Oliveira RW, Diógenes GP, et al. Premotor, nonmotor and motor symptoms of Parkinson s disease: a new clinical state of the art. Ageing Res Rev. 2023;84:101834.
  • 3. Collier TJ, Kanaan NM, Kordower JH. Ageing as a primary risk factor for Parkinson’s disease: evidence from studies of non-human primates. Nat Rev Neurosci. 2011;12:359-366.
  • 4. Coleman C, Martin I. Unraveling Parkinson’s disease neurodegeneration: does aging hold the clues? J Parkinsons Dis. 2022;12:2321-2338.
  • 5. Zampese E, Surmeier DJ. Calcium, bioenergetics, and Parkinson’s disease. Cells. 2020;9:2045.
  • 6. de Rijk MC, Breteler MM, Graveland GA, et al. Prevalence of Parkinson’s disease in the elderly: the Rotterdam Study. Neurology. 1995;45:2143-2146.
  • 7. Chiò A, Magnani C, Schiffer D. Prevalence of Parkinson’s disease in Northwestern Italy: comparison of tracer methodology and clinical ascertainment of cases. Mov Disord. 1998;13:400-405.
  • 8. Kyrozis A, Ghika A, Stathopoulos P, et al. Dietary and lifestyle variables in relation to incidence of Parkinson’s disease in Greece. Eur J Epidemiol. 2013;28:67-77.
  • 9. Ma CL, Su L, Xie JJ, et al. The prevalence and incidence of Parkinson’s disease in China: a systematic review and meta-analysis. J Neural Transm (Vienna). 2014;121:123-134.
  • 10. Hindle JV. Ageing, neurodegeneration and Parkinson’s disease. Age Ageing. 2010;39:156-161.
  • 11. Aarsland D, Kvaløy JT, Andersen K, et al. The effect of age of onset of PD on risk of dementia. J Neurol. 2007;254:38-45.
  • 12. Hely MA, Morris JG, Reid WG, et al. Sydney Multicenter Study of Parkinson’s disease: non-L-dopa-responsive problems dominate at 15 years. Mov Disord. 2005;20:190-199.
  • 13. Aarsland D, Andersen K, Larsen JP, et al. Risk of dementia in Parkinson’s disease: a community-based, prospective study. Neurology. 2001;56:730- 736.
  • 14. Pigott K, Rick J, Xie SX, et al. Longitudinal study of normal cognition in Parkinson disease. Neurology. 2015;85:1276-1282.
  • 15. Elgh E, Domellöf M, Linder J, et al. Cognitive function in early Parkinson’s disease: a population-based study. Eur J Neurol. 2009;16:1278-1284.
  • 16. Aarsland D, Batzu L, Halliday GM, et al. Parkinson disease-associated cognitive impairment. Nat Rev Dis Primers. 2021;7:47.
  • 17. Rodriguez-Oroz MC, Jahanshahi M, Krack P, et al. Initial clinical manifestations of Parkinson’s disease: features and pathophysiological mechanisms. Lancet Neurol. 2009;8:1128-1139.
  • 18. Carbon M, Ma Y, Barnes A, et al. Caudate nucleus: influence of dopaminergic input on sequence learning and brain activation in Parkinsonism. Neuroimage. 2004;21:1497-1507.
  • 19. Polito C, Berti V, Ramat S, et al. Interaction of caudate dopamine depletion and brain metabolic changes with cognitive dysfunction in early Parkinson’s disease. Neurobiol Aging. 2012;33:206.29-39.
  • 20. Ekman U, Eriksson J, Forsgren L, et al. Functional brain activity and presynaptic dopamine uptake in patients with Parkinson’s disease and mild cognitive impairment: a cross-sectional study. Lancet Neurol. 2012;11:679- 687.
  • 21. Jokinen P, Brück A, Aalto S, et al. Impaired cognitive performance in Parkinson’s disease is related to caudate dopaminergic hypofunction and hippocampal atrophy. Parkinsonism Relat Disord. 2009;15:88-93.
  • 22. Bernheimer H, Birkmayer W, Hornykiewicz O, et al. Brain dopamine and the syndromes of Parkinson and Huntington: clinical, morphological and neurochemical correlations. J Neurol Sci. 1973;20:415-455.
  • 23. Sawamoto N, Piccini P, Hotton G, et al. Cognitive deficits and striato-frontal dopamine release in Parkinson’s disease. Brain. 2008;131:1294-1302.
  • 24. Gunning-Dixon FM, Head D, McQuain J, et al. Differential aging of the human striatum: a prospective MR imaging study. AJNR Am J Neuroradiol. 1998;19:1501-1507.
  • 25. Erixon-Lindroth N, Farde L, Wahlin TB, et al. The role of the striatal dopamine transporter in cognitive aging. Psychiatry Res. 2005;138:1-12.
  • 26. Eriksen J, Jørgensen TN, Gether U. Regulation of dopamine transporter function by protein-protein interactions: new discoveries and methodological challenges. J. Neurochem. 2010;113:27-41.
  • 27. Cummings JL, Fine MJ, Grachev ID, et al. Effective and efficient diagnosis of parkinsonism: the role of dopamine transporter SPECT imaging with ioflupane I-123 injection (DaTscan™). Am J Manag Care. 2014;20(5 Suppl):97-109.
  • 28. Ogawa T, Fujii S, Kuya K, et al. Role of neuroimaging on differentiation of Parkinson’s disease and its related diseases. Yonago Acta Med. 2018;61:145- 155.
  • 29. Rukavina K, Mulholland N, Corcoran B, et al. Musculoskeletal pain in Parkinson’s disease: association with dopaminergic deficiency in the caudate nucleus. Eur J Pain. 2024;28:244-251.
  • 30. Jeong SH, Park CW, Lee HS, et al. Patterns of striatal dopamine depletion and motor deficits in de novo Parkinson’s disease. J Neural Transm (Vienna). 2023;130:19-28.
  • 31. Arnaldi D, Campus C, Ferrara M, et al. What predicts cognitive decline in de novo Parkinson’s disease? Neurobiol Aging. 2012;33:1127.
  • 32. Schrag A, Siddiqui UF, Anastasiou Z, et al. Clinical variables and biomarkers in prediction of cognitive impairment in patients with newly diagnosed Parkinson’s disease: a cohort study. Lancet Neurol. 2017;16:66-75.
  • 33. Caspell-Garcia C, Simuni T, Tosun-Turgut D, et al. Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease. PLoS One. 017;12:0175674.
  • 34. Lubomski M, Davis RL, Sue CM. Cognitive influences in Parkinson’s disease patients and their caregivers: perspectives from an Australian cohort. Front Neurol. 2021;12:673816.
  • 35. Parkinson‘s Progression Markers Initative. Available from: https://www. ppmi-info.org/data 36. Mozley LH, Gur RC, Mozley PD, et al. Striatal dopamine transporters and cognitive functioning in healthy men and women. Am J Psychiatry. 2001;158:1492-1499.
  • 37. Kierzynka A, Kaźmierski R, Kozubski W. Educational level and cognitive impairment in patients with Parkinson disease. Neurol Neurochir Pol. 2011;45:24-31.
  • 38. Hayes AF. Beyond Baron and Kenny: Statistical Mediation Analysis in the New Millennium. Commun Monogr. 2009;76:408-420.
  • 39. Çırak M, Yağmurlu K, Kearns KN, et al. The Caudate Nucleus: Its Connections, Surgical Implications, and Related Complications. World Neurosurg. 2020;139:428-438.
  • 40. Grahn JA, Parkinson JA, Owen AM. The cognitive functions of the caudate nucleus. Prog Neurobiol. 2008;86:141-155.
  • 41. Arnaldi D, Campus C, Ferrara M, et al. What predicts cognitive decline in de novo Parkinson’s disease? Neurobiol Aging. 2012;33:1127.
  • 42. Ravina B, Marek K, Eberly S, et al. Dopamine transporter imaging is associated with long-term outcomes in Parkinson’s disease. Mov Disord. 2012;27:1392-1397.
  • 43. Nobili F, Campus C, Arnaldi D, et al. Cognitive-nigrostriatal relationships in de novo, drug-naïve Parkinson’s disease patients: a [I-123]FP-CIT SPECT study. Mov Disord. 2010;25:35-43.
  • 44. Chung SJ, Yoo HS, Oh JS, et al. Effect of striatal dopamine depletion on cognition in de novo Parkinson’s disease. Parkinsonism Relat Disord. 2018;51:43-48.
  • 45. Li H, Hirano S, Furukawa S, et al. The Relationship Between the Striatal Dopaminergic Neuronal and Cognitive Function With Aging. Front Aging Neurosci. 2020;12:41.
  • 46. Volkow ND, Gur RC, Wang GJ, et al. Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals. Am J Psychiatry. 1998;155:344-349.
  • 47. Scherfler C, Schwarz J, Antonini A, et al. Role of DAT-SPECT in the diagnostic work up of parkinsonism. Mov Disord. 2007;22:1229-1238.
  • 48. Shaikh A, Ahmad F, Teoh SL, et al. Targeting dopamine transporter to ameliorate cognitive deficits in Alzheimer’s disease. Front Cell Neurosci. 2023;17:1292858.
  • 49. Cools R. Dopaminergic control of the striatum for high-level cognition. Curr Opin Neurobiol. 2011;21:402-407.
  • 50. Strafella AP, Paus T, Barrett J, et al. Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus. J Neurosci. 2001;21:RC157.
  • 51. Bondi MW, Kaszniak AW, Bayles KA, et al. Contributions of frontal system dysfunction to memory and perceptual abilities in Parkinson’s disease. Neuropsychology. 1993;7(1):89-102.
  • 52. Herman JP, Arcizet F, Krauzlis RJ. Attention-related modulation of caudate neurons depends on superior colliculus activity. Elife. 2020;9:53998.

Parkinson Hastalarında Kaudat Çekirdek Dopaminerjik Aktivitesinin Yaş ve Bilişsel İşlevler Arasındaki İlişkiye Aracılık Etkisi

Year 2024, Volume: 77 Issue: 4, 367 - 373, 31.12.2024

Abstract

Amaç: İlerleyen yaş, Parkinson hastalığı için birincil risk faktörüdür. Parkinson hastalarında, dopaminerjik aktivite bozulur ve bilişsel işlev bozuklukları görülür. Bu çalışmanın amacı, Parkinson hastalarında yaş ve biliş ilişkisinde, kaudat çekirdek dopamin taşıyıcısı bağlanma skorunun aracılık etkisinin araştırılmasıdır.

Gereç ve Yöntem: Michael J. Fox Derneğinin erişime açık veritabanı kullanılmış, 1.099 Parkinson hastasının verilerine erişim sağlanmıştır. Hastaların bilişsel işlev puanları ve kaudat çekirdek dopaminerjik aktivitesini değerlendiren tek foton emisyon tomografisi bulguları kullanılmıştır.

Bulgular: Kaudat çekirdek dopamin taşıyıcısı bağlanma skoru, yaş ile dikkat, işlem hızı, dilsel işlev, çalışma belleği, sözel epizodik bellek ve görseluzamsal işlevler arasındaki ilişkiye aracılık etmiştir.

Sonuç: Yaş ve Parkinson hastalığının kümülatif nörodejeneratif etkisi, bilişsel işlevlerin takibini gerektirmektedir. Bu çalışma, Parkinson hastalığında bilişsel işlevlerin tanı, takip ve tedavisinde, kaudat çekirdek dopaminerjik aktivitesinin dikkate alınmasının önemini vurgulamaktadır.

Project Number

-

References

  • 1. GBD 2016 Parkinson’s Disease Collaborators. Global, regional, and national burden of Parkinson’s disease, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17:939-953.
  • 2. Leite Silva ABR, Gonçalves de Oliveira RW, Diógenes GP, et al. Premotor, nonmotor and motor symptoms of Parkinson s disease: a new clinical state of the art. Ageing Res Rev. 2023;84:101834.
  • 3. Collier TJ, Kanaan NM, Kordower JH. Ageing as a primary risk factor for Parkinson’s disease: evidence from studies of non-human primates. Nat Rev Neurosci. 2011;12:359-366.
  • 4. Coleman C, Martin I. Unraveling Parkinson’s disease neurodegeneration: does aging hold the clues? J Parkinsons Dis. 2022;12:2321-2338.
  • 5. Zampese E, Surmeier DJ. Calcium, bioenergetics, and Parkinson’s disease. Cells. 2020;9:2045.
  • 6. de Rijk MC, Breteler MM, Graveland GA, et al. Prevalence of Parkinson’s disease in the elderly: the Rotterdam Study. Neurology. 1995;45:2143-2146.
  • 7. Chiò A, Magnani C, Schiffer D. Prevalence of Parkinson’s disease in Northwestern Italy: comparison of tracer methodology and clinical ascertainment of cases. Mov Disord. 1998;13:400-405.
  • 8. Kyrozis A, Ghika A, Stathopoulos P, et al. Dietary and lifestyle variables in relation to incidence of Parkinson’s disease in Greece. Eur J Epidemiol. 2013;28:67-77.
  • 9. Ma CL, Su L, Xie JJ, et al. The prevalence and incidence of Parkinson’s disease in China: a systematic review and meta-analysis. J Neural Transm (Vienna). 2014;121:123-134.
  • 10. Hindle JV. Ageing, neurodegeneration and Parkinson’s disease. Age Ageing. 2010;39:156-161.
  • 11. Aarsland D, Kvaløy JT, Andersen K, et al. The effect of age of onset of PD on risk of dementia. J Neurol. 2007;254:38-45.
  • 12. Hely MA, Morris JG, Reid WG, et al. Sydney Multicenter Study of Parkinson’s disease: non-L-dopa-responsive problems dominate at 15 years. Mov Disord. 2005;20:190-199.
  • 13. Aarsland D, Andersen K, Larsen JP, et al. Risk of dementia in Parkinson’s disease: a community-based, prospective study. Neurology. 2001;56:730- 736.
  • 14. Pigott K, Rick J, Xie SX, et al. Longitudinal study of normal cognition in Parkinson disease. Neurology. 2015;85:1276-1282.
  • 15. Elgh E, Domellöf M, Linder J, et al. Cognitive function in early Parkinson’s disease: a population-based study. Eur J Neurol. 2009;16:1278-1284.
  • 16. Aarsland D, Batzu L, Halliday GM, et al. Parkinson disease-associated cognitive impairment. Nat Rev Dis Primers. 2021;7:47.
  • 17. Rodriguez-Oroz MC, Jahanshahi M, Krack P, et al. Initial clinical manifestations of Parkinson’s disease: features and pathophysiological mechanisms. Lancet Neurol. 2009;8:1128-1139.
  • 18. Carbon M, Ma Y, Barnes A, et al. Caudate nucleus: influence of dopaminergic input on sequence learning and brain activation in Parkinsonism. Neuroimage. 2004;21:1497-1507.
  • 19. Polito C, Berti V, Ramat S, et al. Interaction of caudate dopamine depletion and brain metabolic changes with cognitive dysfunction in early Parkinson’s disease. Neurobiol Aging. 2012;33:206.29-39.
  • 20. Ekman U, Eriksson J, Forsgren L, et al. Functional brain activity and presynaptic dopamine uptake in patients with Parkinson’s disease and mild cognitive impairment: a cross-sectional study. Lancet Neurol. 2012;11:679- 687.
  • 21. Jokinen P, Brück A, Aalto S, et al. Impaired cognitive performance in Parkinson’s disease is related to caudate dopaminergic hypofunction and hippocampal atrophy. Parkinsonism Relat Disord. 2009;15:88-93.
  • 22. Bernheimer H, Birkmayer W, Hornykiewicz O, et al. Brain dopamine and the syndromes of Parkinson and Huntington: clinical, morphological and neurochemical correlations. J Neurol Sci. 1973;20:415-455.
  • 23. Sawamoto N, Piccini P, Hotton G, et al. Cognitive deficits and striato-frontal dopamine release in Parkinson’s disease. Brain. 2008;131:1294-1302.
  • 24. Gunning-Dixon FM, Head D, McQuain J, et al. Differential aging of the human striatum: a prospective MR imaging study. AJNR Am J Neuroradiol. 1998;19:1501-1507.
  • 25. Erixon-Lindroth N, Farde L, Wahlin TB, et al. The role of the striatal dopamine transporter in cognitive aging. Psychiatry Res. 2005;138:1-12.
  • 26. Eriksen J, Jørgensen TN, Gether U. Regulation of dopamine transporter function by protein-protein interactions: new discoveries and methodological challenges. J. Neurochem. 2010;113:27-41.
  • 27. Cummings JL, Fine MJ, Grachev ID, et al. Effective and efficient diagnosis of parkinsonism: the role of dopamine transporter SPECT imaging with ioflupane I-123 injection (DaTscan™). Am J Manag Care. 2014;20(5 Suppl):97-109.
  • 28. Ogawa T, Fujii S, Kuya K, et al. Role of neuroimaging on differentiation of Parkinson’s disease and its related diseases. Yonago Acta Med. 2018;61:145- 155.
  • 29. Rukavina K, Mulholland N, Corcoran B, et al. Musculoskeletal pain in Parkinson’s disease: association with dopaminergic deficiency in the caudate nucleus. Eur J Pain. 2024;28:244-251.
  • 30. Jeong SH, Park CW, Lee HS, et al. Patterns of striatal dopamine depletion and motor deficits in de novo Parkinson’s disease. J Neural Transm (Vienna). 2023;130:19-28.
  • 31. Arnaldi D, Campus C, Ferrara M, et al. What predicts cognitive decline in de novo Parkinson’s disease? Neurobiol Aging. 2012;33:1127.
  • 32. Schrag A, Siddiqui UF, Anastasiou Z, et al. Clinical variables and biomarkers in prediction of cognitive impairment in patients with newly diagnosed Parkinson’s disease: a cohort study. Lancet Neurol. 2017;16:66-75.
  • 33. Caspell-Garcia C, Simuni T, Tosun-Turgut D, et al. Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease. PLoS One. 017;12:0175674.
  • 34. Lubomski M, Davis RL, Sue CM. Cognitive influences in Parkinson’s disease patients and their caregivers: perspectives from an Australian cohort. Front Neurol. 2021;12:673816.
  • 35. Parkinson‘s Progression Markers Initative. Available from: https://www. ppmi-info.org/data 36. Mozley LH, Gur RC, Mozley PD, et al. Striatal dopamine transporters and cognitive functioning in healthy men and women. Am J Psychiatry. 2001;158:1492-1499.
  • 37. Kierzynka A, Kaźmierski R, Kozubski W. Educational level and cognitive impairment in patients with Parkinson disease. Neurol Neurochir Pol. 2011;45:24-31.
  • 38. Hayes AF. Beyond Baron and Kenny: Statistical Mediation Analysis in the New Millennium. Commun Monogr. 2009;76:408-420.
  • 39. Çırak M, Yağmurlu K, Kearns KN, et al. The Caudate Nucleus: Its Connections, Surgical Implications, and Related Complications. World Neurosurg. 2020;139:428-438.
  • 40. Grahn JA, Parkinson JA, Owen AM. The cognitive functions of the caudate nucleus. Prog Neurobiol. 2008;86:141-155.
  • 41. Arnaldi D, Campus C, Ferrara M, et al. What predicts cognitive decline in de novo Parkinson’s disease? Neurobiol Aging. 2012;33:1127.
  • 42. Ravina B, Marek K, Eberly S, et al. Dopamine transporter imaging is associated with long-term outcomes in Parkinson’s disease. Mov Disord. 2012;27:1392-1397.
  • 43. Nobili F, Campus C, Arnaldi D, et al. Cognitive-nigrostriatal relationships in de novo, drug-naïve Parkinson’s disease patients: a [I-123]FP-CIT SPECT study. Mov Disord. 2010;25:35-43.
  • 44. Chung SJ, Yoo HS, Oh JS, et al. Effect of striatal dopamine depletion on cognition in de novo Parkinson’s disease. Parkinsonism Relat Disord. 2018;51:43-48.
  • 45. Li H, Hirano S, Furukawa S, et al. The Relationship Between the Striatal Dopaminergic Neuronal and Cognitive Function With Aging. Front Aging Neurosci. 2020;12:41.
  • 46. Volkow ND, Gur RC, Wang GJ, et al. Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals. Am J Psychiatry. 1998;155:344-349.
  • 47. Scherfler C, Schwarz J, Antonini A, et al. Role of DAT-SPECT in the diagnostic work up of parkinsonism. Mov Disord. 2007;22:1229-1238.
  • 48. Shaikh A, Ahmad F, Teoh SL, et al. Targeting dopamine transporter to ameliorate cognitive deficits in Alzheimer’s disease. Front Cell Neurosci. 2023;17:1292858.
  • 49. Cools R. Dopaminergic control of the striatum for high-level cognition. Curr Opin Neurobiol. 2011;21:402-407.
  • 50. Strafella AP, Paus T, Barrett J, et al. Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus. J Neurosci. 2001;21:RC157.
  • 51. Bondi MW, Kaszniak AW, Bayles KA, et al. Contributions of frontal system dysfunction to memory and perceptual abilities in Parkinson’s disease. Neuropsychology. 1993;7(1):89-102.
  • 52. Herman JP, Arcizet F, Krauzlis RJ. Attention-related modulation of caudate neurons depends on superior colliculus activity. Elife. 2020;9:53998.
There are 51 citations in total.

Details

Primary Language English
Subjects Neurology and Neuromuscular Diseases
Journal Section Research Article
Authors

Evrim Gökçe 0000-0003-1548-8785

Project Number -
Submission Date July 29, 2024
Acceptance Date October 22, 2024
Publication Date December 31, 2024
Published in Issue Year 2024 Volume: 77 Issue: 4

Cite

APA Gökçe, E. (2024). The Mediating Effect of Caudate Nucleus Dopaminergic Activity on the Relationship Between Age and Cognitive Functions in Parkinson’s Disease Patients. Ankara Üniversitesi Tıp Fakültesi Mecmuası, 77(4), 367-373. https://doi.org/10.4274/atfm.galenos.2024.15010
AMA Gökçe E. The Mediating Effect of Caudate Nucleus Dopaminergic Activity on the Relationship Between Age and Cognitive Functions in Parkinson’s Disease Patients. Ankara Üniversitesi Tıp Fakültesi Mecmuası. December 2024;77(4):367-373. doi:10.4274/atfm.galenos.2024.15010
Chicago Gökçe, Evrim. “The Mediating Effect of Caudate Nucleus Dopaminergic Activity on the Relationship Between Age and Cognitive Functions in Parkinson’s Disease Patients”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 77, no. 4 (December 2024): 367-73. https://doi.org/10.4274/atfm.galenos.2024.15010.
EndNote Gökçe E (December 1, 2024) The Mediating Effect of Caudate Nucleus Dopaminergic Activity on the Relationship Between Age and Cognitive Functions in Parkinson’s Disease Patients. Ankara Üniversitesi Tıp Fakültesi Mecmuası 77 4 367–373.
IEEE E. Gökçe, “The Mediating Effect of Caudate Nucleus Dopaminergic Activity on the Relationship Between Age and Cognitive Functions in Parkinson’s Disease Patients”, Ankara Üniversitesi Tıp Fakültesi Mecmuası, vol. 77, no. 4, pp. 367–373, 2024, doi: 10.4274/atfm.galenos.2024.15010.
ISNAD Gökçe, Evrim. “The Mediating Effect of Caudate Nucleus Dopaminergic Activity on the Relationship Between Age and Cognitive Functions in Parkinson’s Disease Patients”. Ankara Üniversitesi Tıp Fakültesi Mecmuası 77/4 (December2024), 367-373. https://doi.org/10.4274/atfm.galenos.2024.15010.
JAMA Gökçe E. The Mediating Effect of Caudate Nucleus Dopaminergic Activity on the Relationship Between Age and Cognitive Functions in Parkinson’s Disease Patients. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 2024;77:367–373.
MLA Gökçe, Evrim. “The Mediating Effect of Caudate Nucleus Dopaminergic Activity on the Relationship Between Age and Cognitive Functions in Parkinson’s Disease Patients”. Ankara Üniversitesi Tıp Fakültesi Mecmuası, vol. 77, no. 4, 2024, pp. 367-73, doi:10.4274/atfm.galenos.2024.15010.
Vancouver Gökçe E. The Mediating Effect of Caudate Nucleus Dopaminergic Activity on the Relationship Between Age and Cognitive Functions in Parkinson’s Disease Patients. Ankara Üniversitesi Tıp Fakültesi Mecmuası. 2024;77(4):367-73.