Download PDF
Pharmacopsychiatry 2025; 58(01): 5-13
DOI: 10.1055/a-2446-6877
Original Paper

Impact of Parkinson Medication on Neuropsychiatric and Neurocognitive Symptoms in Patients with Advanced Parkinson Disease Prior to Deep Brain Stimulation

Jan Haeckert
1   Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, Augsburg, Germany
,
Astrid Roeh
1   Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, Augsburg, Germany
,
Susanne Karch
2   Department of Psychiatry and Psychotherapy, University Hospital Munich, LMU Munich, München, Germany
,
Thomas Koeglsperger
3   Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany
4   Department of Translational Brain Research, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
,
Alkomiet Hasan
1   Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, Augsburg, Germany
5   DZPG (German Center for Mental Health), partner site Munich/Augsburg, Germany
,
Irina Papazova
1   Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, Augsburg, Germany
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

Introduction This study evaluates the impact of Parkinson disease (PD) medication in advanced PD on neuropsychological performance, psychiatric symptoms, impulsivity and the quality of life. In the 4-year period 27 patients with advanced PD, scheduled for deep brain stimulation (DBS) surgery (N=27, mean age: 58.9±7.1, disease duration: 10.0 years±4.2) were examined preoperatively. We hypothesized that a high dosage of PD medication or current use of dopamine agonists affect cognitive functioning and psychiatric wellbeing.

Methods We performed two subgroup analyses with low versus high levodopa-equivalent Dosage (LED) medication and without versus with dopaminagonistic medication.

Results The neuropsychological testing revealed significant differences in the verbal learn- and memory-test (VLMT) during the learning passage (U=36.500, Z=− 2.475, p=0.012) and in the subtest of the semantic fluency of Regensburg verbal fluency test (RWT) (t(25)=− 2.066, p=0.049) with better results for patients without dopaminagonistic medication. Pearson correlation analyses of LED in correlation with the clinical and cognitive dependent variables showed a significant higher PANSS total score in patients with higher LED medication (r=0.491, p=0.009). In addition, lower LED treatment was associated with significant higher scores in the impulsivity perseverance subtest (r=− 0.509, p=0.008).

Discussion In conclusion, we found lower LEDs to be correlated with a better perseverance in the impulsivity test and additional treatment with a dopamine agonist influenced some verbal learning tasks and the PANSS total score in patients with advanced PD. This should be considered prior to DBS surgery.

Keywords

advanced Parkinson disease - Parkinson medication - dopamine agonists - neurocognitive deficits - impulsivity

Supplementary Material



Publication History

Received: 09 March 2024

Accepted after revision: 23 July 2024

Article published online:
21 November 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Poewe W, Seppi K, Tanner CM. et al. Parkinson disease. Nat Rev Dis Primer 2017; 3: 17013
    CrossrefPubMedSearch in Google Scholar
  • 2 Hughes AJ, Daniel SE, Kilford L. et al. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: A clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992; 55: 181-184
    CrossrefPubMedSearch in Google Scholar
  • 3 Yang W, Hamilton JL, Kopil C. et al. Current and projected future economic burden of Parkinson’s disease in the U.S. Npj Park Dis. 2020; 6: 15
    CrossrefPubMedSearch in Google Scholar
  • 4 Schuepbach WMM, Rau J, Knudsen K. et al. Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med 2013; 368: 610-622
    CrossrefPubMedSearch in Google Scholar
  • 5 Broeders M, de Bie RMA, Velseboer DC. et al. Evolution of mild cognitive impairment in Parkinson disease. Neurology 2013; 81: 346-352
    CrossrefPubMedSearch in Google Scholar
  • 6 Aarsland D, Creese B, Politis M. et al. Cognitive decline in Parkinson disease. Nat Rev Neurol 2017; 13: 217-231
    CrossrefPubMedSearch in Google Scholar
  • 7 Foltynie T, Brayne CEG, Robbins TW. et al. The cognitive ability of an incident cohort of Parkinson’s patients in the UK. The CamPaIGN study. Brain 2004; 127: 550-560
    CrossrefPubMedSearch in Google Scholar
  • 8 Williams-Gray CH, Foltynie T, Brayne CEG. et al. Evolution of cognitive dysfunction in an incident Parkinson’s disease cohort. Brain 2007; 130: 1787-1798
    CrossrefPubMedSearch in Google Scholar
  • 9 Cools R. Dopaminergic modulation of cognitive function-implications for l-DOPA treatment in Parkinson’s disease. Neurosci Biobehav Rev 2006; 30: 1-23
    CrossrefPubMedSearch in Google Scholar
  • 10 Voon V, Kubu C, Krack P. et al. Deep brain stimulation: Neuropsychological and neuropsychiatric issues. Mov Disord 2006; 21: S305-S327
    CrossrefPubMedSearch in Google Scholar
  • 11 Munhoz RP, Picillo M, Fox SH. et al. Eligibility criteria for deep brain stimulation in Parkinson’s disease, tremor, and dystonia. Can J Neurol Sci J Can Sci Neurol 2016; 43: 462-471
    CrossrefPubMedSearch in Google Scholar
  • 12 Massano J, Garrett C. Deep brain stimulation and cognitive decline in Parkinson’s disease: A clinical review. Front Neurol 2012; 3
    CrossrefPubMedSearch in Google Scholar
  • 13 Höglinger G, Trenkwalder C. et al Parkinson-Krankheit, S2k-Leitlinie, in: Deutsche Gesellschaft für Neurologie (Hrsg.). Leitlinien für Diagnostik und Therapie in der Neurologie. 2023
    PubMedSearch in Google Scholar
  • 14 Nilsson FM, Kessing LV, Sørensen TM. et al. Major depressive disorder in Parkinson’s disease: A register-based study. Acta Psychiatr Scand 2002; 106: 202-211
    CrossrefPubMedSearch in Google Scholar
  • 15 Aarsland D, Påhlhagen S, Ballard CG. et al. Depression in Parkinson disease – epidemiology, mechanisms and management. Nat Rev Neurol 2012; 8: 35-47
    CrossrefPubMedSearch in Google Scholar
  • 16 Voon V, Krack P, Lang AE. et al. A multicentre study on suicide outcomes following subthalamic stimulation for Parkinson’s disease. Brain 2008; 131: 2720-2728
    CrossrefPubMedSearch in Google Scholar
  • 17 Follett KA, Weaver FM, Stern M. et al. Pallidal versus subthalamic deep-brain stimulation for Parkinson’s disease. N Engl J Med 2010; 362: 2077-2091
    CrossrefPubMedSearch in Google Scholar
  • 18 Samudra N, Patel N, Womack KB. et al. Psychosis in Parkinson disease: A review of etiology, phenomenology, and management. Drugs Aging 2016; 33: 855-863
    CrossrefPubMedSearch in Google Scholar
  • 19 Schaeffer E, Berg D. Dopaminergic therapies for non-motor symptoms in Parkinson’s disease. CNS Drugs 2017; 31: 551-570
    CrossrefPubMedSearch in Google Scholar
  • 20 Lehrl S. Mehrfach-Wortschatz-Intelligenztest:. MWT-B 5. Aufl., Balingen: Spitta. 2005
    PubMedSearch in Google Scholar
  • 21 Randolph C. Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Psychological Corporation San Antonio, TX. 1998
    PubMedSearch in Google Scholar
  • 22 Gold JM, Carpenter C, Randolph C. et al. Auditory working memory and Wisconsin Card Sorting Test performance in schizophrenia. Arch Gen Psychiatry 1997; 54: 159-165
    CrossrefPubMedSearch in Google Scholar
  • 23 Helmstaedter C, Lendt M, Lux S. Veerbaler Lern- und Merkfähigkeitstest: VLMT. Göttingen:. Beltz Test. 2001
    PubMedSearch in Google Scholar
  • 24 Aschenbrenner S, Tucha O, Lange KW. Regensburger Wortflüssigkeits-Test: RWT. Göttingen; Bern; Toronto; Seattle:. Hogrefe, Verl. Für Psychologie. 2000
    PubMedSearch in Google Scholar
  • 25 Kohler J, Beck U, Hohnecker B. Neuropsychological assessment of basic planning competence. Journal of the International Neuropsychological Society. 2003 9. 519
    PubMedSearch in Google Scholar
  • 26 Wittchen -U H, Zaudig M, Fydrich T. Strukturiertes klinisches Interview für DSM-IV: SKID; eine deutschsprachige, erweiterte Bearbeitung der amerikanischen Originalversion des SCID. Göttingen [u.a.]: Hogrefe. 1997
    PubMedSearch in Google Scholar
  • 27 Jenkinson C, Fitzpatrick R, Peto V. et al. The Parkinson’s Disease Questionnaire (PDQ-39): Development and validation of a Parkinson’s disease summary index score. Age Ageing 1997; 26: 353-357
    CrossrefPubMedSearch in Google Scholar
  • 28 Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987 13. 261-276
    PubMedSearch in Google Scholar
  • 29 Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23: 56
    CrossrefPubMedSearch in Google Scholar
  • 30 Beck AT, Steer RA, Brown GK. Manual for The Beck Depression Inventory Second Edition (BDI-II). San Antonio: Psychological Corporation. 1996 a
    PubMedSearch in Google Scholar
  • 31 Yesavage JA. Geriatric depression scale. Psychopharmacol Bull 1988; 24: 709-711
    PubMedSearch in Google Scholar
  • 32 Whiteside SP, Lynam DR. The five factor model and impulsivity: Using a structural model of personality to understand impulsivity. Personal Individ Differ 2001; 30: 669-689
    CrossrefPubMedSearch in Google Scholar
  • 33 Goetz CG, Tilley BC, Shaftman SR. et al. Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): Scale presentation and clinimetric testing results. Mov Disord 2008; 23: 2129-2170
    CrossrefPubMedSearch in Google Scholar
  • 34 Schade S, Mollenhauer B, Trenkwalder C. Levodopa equivalent dose conversion factors: An updated proposal including opicapone and safinamide. Mov Disord Clin Pract 2020; 7: 343-345
    CrossrefPubMedSearch in Google Scholar
  • 35 Tomlinson CL, Stowe R, Patel S. et al. Systematic review of levodopa dose equivalency reporting in Parkinson’s disease: Systematic review of LED reporting in PD. Mov Disord 2010; 25: 2649-2653
    CrossrefPubMedSearch in Google Scholar
  • 36 Hagell P, Nygren C. The 39 item Parkinson’s disease questionnaire (PDQ-39) revisited: Implications for evidence based medicine. J Neurol Neurosurg Amp Psychiatry 2007; 78: 1191-1198
    CrossrefPubMedSearch in Google Scholar
  • 37 Martínez-Martín P, Rodríguez-Blázquez C, Mario Alvarez et al. Parkinson’s disease severity levels and MDS-Unified Parkinson’s Disease Rating Scale. Parkinsonism Relat Disord 2015; 21: 50-54
    CrossrefPubMedSearch in Google Scholar
  • 38 Herrera E, Cuetos F, Ribacoba R. Verbal fluency in Parkinson’s disease patients on/off dopamine medication. Neuropsychologia 2012; 50: 3636-3640
    CrossrefPubMedSearch in Google Scholar
  • 39 Brusa L, Pavino V, Massimetti MC. et al. The effect of dopamine agonists on cognitive functions in non-demented early-mild Parkinson’s disease patients. Funct Neurol 2013; 28: 13-17
    PubMedSearch in Google Scholar
  • 40 Santangelo G, Piscopo F, Barone P. et al. Personality in Parkinson’s disease: Clinical, behavioural and cognitive correlates. J Neurol Sci 2017; 374: 17-25
    CrossrefPubMedSearch in Google Scholar
  • 41 Volpato C, Signorini M, Meneghello F. et al. Cognitive and personality features in Parkinson disease: 2 sides of the same coin?. Cogn Behav Neurol 2009; 22: 258-263
    CrossrefPubMedSearch in Google Scholar
  • 42 Bodi N, Keri S, Nagy H. et al. Reward-learning and the novelty-seeking personality: A between- and within-subjects study of the effects of dopamine agonists on young Parkinson’s patients. Brain 2009; 132: 2385-2395
    CrossrefPubMedSearch in Google Scholar
  • 43 Sieurin J, Gustavsson P, Weibull CE. et al. Personality traits and the risk for Parkinson disease: A prospective study. Eur J Epidemiol 2016; 31: 169-175
    CrossrefPubMedSearch in Google Scholar
  • 44 Evans AH, Lawrence AD, Potts J. et al. Factors influencing susceptibility to compulsive dopaminergic drug use in Parkinson disease. Neurology 2005; 65: 1570-1574
    CrossrefPubMedSearch in Google Scholar
  • 45 Voon V, Fernagut P-O, Wickens J. et al. Chronic dopaminergic stimulation in Parkinson’s disease: From dyskinesias to impulse control disorders. Lancet Neurol 2009; 8: 1140-1149
    CrossrefPubMedSearch in Google Scholar
  • 46 Weintraub D. Impulse control disorders in Parkinson’s disease: Prevalence and possible risk factors. Parkinsonism Relat Disord 2009; 15: S110-S113
    CrossrefPubMedSearch in Google Scholar
  • 47 Antonelli F, Ko JH, Miyasaki J. et al. Dopamine-agonists and impulsivity in Parkinson’s disease: Impulsive choices vs. impulsive actions. Hum Brain Mapp 2014; 35: 2499-2506
    CrossrefPubMedSearch in Google Scholar
  • 48 Fénelon G, Alves G. Epidemiology of psychosis in Parkinson’s disease. J Neurol Sci 2010; 289: 12-17
    CrossrefPubMedSearch in Google Scholar
  • 49 Williams DR, Warren JD, Lees AJ. Using the presence of visual hallucinations to differentiate Parkinson’s disease from atypical parkinsonism. J Neurol Neurosurg Psychiatry 2007; 79: 652-655
    CrossrefPubMedSearch in Google Scholar
  • 50 Pollak P. Clozapine in drug induced psychosis in Parkinson’s disease: A randomised, placebo controlled study with open follow up. J Neurol Neurosurg Psychiatry 2004; 75: 689-695
    CrossrefPubMedSearch in Google Scholar
  • 51 Munhoz RP, Teive HA, Eleftherohorinou H. et al. Demographic and motor features associated with the occurrence of neuropsychiatric and sleep complications of Parkinson’s disease. J Neurol Neurosurg Psychiatry 2013; 84: 883-887
    CrossrefPubMedSearch in Google Scholar
  • 52 Aarsland D, Marsh L, Schrag A. Neuropsychiatric symptoms in Parkinson’s disease. Mov Disord 2009; 24: 2175-2186
    CrossrefPubMedSearch in Google Scholar
  • 53 Ishihara L, Brayne C. A systematic review of depression and mental illness preceding Parkinson’s disease. Acta Neurol Scand 2006; 113: 211-220
    CrossrefPubMedSearch in Google Scholar
  • 54 Laux G. Parkinson and depression: Review and outlook. J Neural Transm 2022; 129: 601-608
    CrossrefPubMedSearch in Google Scholar
  • 55 Leentjens AF. The role of dopamine agonists in the treatment of depression in patients with Parkinson’s disease: A systematic review. Drugs 2011; 71: 273-286
    CrossrefPubMedSearch in Google Scholar
  • 56 MacCallum RC, Zhang S, Preacher KJ. et al. On the practice of dichotomization of quantitative variables. Psychol Methods 2002; 7: 19-40
    CrossrefPubMedSearch in Google Scholar