Skip to main content

Advertisement

SpringerLink
Log in

Cognitive and behavioral disorders in Parkinson’s disease: an update. I: cognitive impairments

  • Review Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by motor symptoms such as rigidity, rest tremor, and bradykinesia. However, a growing body of evidence demonstrated that PD encompasses several non-motor disturbances as well, such as cognitive impairment. Cognitive defects can be present since early stages of the disease but tend to dominate the clinical picture as the disease progresses. Around 40% of patients with PD present with cognitive impairments in several cognitive domains including attention, working memory and executive functions, language, visuospatial skills, and episodic memory; in later stages of the disease, cognitive defects and associated behavioral disorders concur to determine clinically relevant PD-associated dementia. Part of these defects is ascribed to a dopamine-dependent dysfunction of fronto-striatal pathways, but there is a considerable heterogeneity in the cognitive impairments as well as a suggestion of the role of other neurotransmitter systems, such as the cholinergic one, mainly responsible for Parkinson-dementia syndrome. In this paper, we review recent literature with particular attention to the last 5 years on the main cognitive deficits described in PD patients as well as on the hypothesized neuro-functional substrate of such impairments. Finally, we provide some suggestions on how to test cognitive functions in PD appropriately.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Schapira AHV, Chaudhuri KR, Jenner P (2017) Non-motor features of Parkinson disease. Nat Rev Neurosci. https://doi.org/10.1038/nrn.2017.62

  2. Schrag A, Hovris A, Morley D, Quinn N, Jahanshahi M (2006) Caregiver-burden in Parkinson’s disease is closely associated with psychiatric symptoms, falls, and disability. Park Relat Disord 12:35–41

    Article  Google Scholar 

  3. Marras C, Chaudhuri KR (2016) Nonmotor features of Parkinson’s disease subtypes. Mov Disord 31:1095–1102

    Article  CAS  PubMed  Google Scholar 

  4. Przedborski S (2017) The two-century journey of Parkinson disease research. Nat Rev Neurosci 18:251–259. https://doi.org/10.1038/nrn.2017.25

    Article  CAS  PubMed  Google Scholar 

  5. Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, Schrag AE, Lang AE (2017) Parkinson disease. Nat Rev Dis Primers 3:17013. https://doi.org/10.1038/nrdp.2017.13

    Article  PubMed  Google Scholar 

  6. Jahanshahi M, Obeso I, Rothwell JC, Obeso JA (2015) A fronto-striato-subthalamic-pallidal network for goal-directed and habitual inhibition. Nat Rev Neurosci 16:719–732. https://doi.org/10.1038/nrn4038

    Article  CAS  PubMed  Google Scholar 

  7. DeLong MR (1990) Primate models of movement disorders of basal ganglia origin. Trends Neurosci 13:281–285

    Article  CAS  PubMed  Google Scholar 

  8. Calabresi P, Picconi B, Tozzi A, Ghiglieri V, Di Filippo M (2014) Direct and indirect pathways of basal ganglia: a critical reappraisal. Nat Neurosci 17:1022–1030. https://doi.org/10.1038/nn.3743

    Article  CAS  PubMed  Google Scholar 

  9. Xu J, Zhang J, Wang J, Li G, Hu Q, Zhang Y (2016) Abnormal fronto-striatal functional connectivity in Parkinson’s disease. Neurosci Lett 613:66–71. https://doi.org/10.1016/j.neulet.2015.12.041

    Article  CAS  PubMed  Google Scholar 

  10. Nagano-Saito A, Al-Azzawi MS, Hanganu A et al (2016) Patterns of longitudinal neural activity linked to different cognitive profiles in Parkinson’s disease. Front Aging Neurosci 8:275

    Article  PubMed  PubMed Central  Google Scholar 

  11. Wile DJ, Agarwal PA, Schulzer M et al (2017) Serotonin and dopamine transporter PET changes in the premotor phase of LRRK2 parkinsonism: cross-sectional studies. Lancet Neurol 16:351–359

    Article  CAS  PubMed  Google Scholar 

  12. Ye Z, Altena E, Nombela C et al (2015) Selective serotonin reuptake inhibition modulates response inhibition in Parkinson’s disease. Brain 137:1145–1155

    Article  Google Scholar 

  13. Bohnen EJ, Kaufer DI, Ivanco LS et al (2003) Cortical cholinergic function is more severely affected in parkinsonian dementia than in Alzheimer disease: an in vivo positron emission tomographic study. Arch Neurol 60:1745–1748

    Article  PubMed  Google Scholar 

  14. Litvan I, Goldman JG, Tröster AI et al (2012) Diagnostic criteria for mild cognitive impairment in Parkinson’s disease: Movement Disorder Society Task Force guidelines. Mov Disord 27:349–356. https://doi.org/10.1002/mds.24893

    Article  PubMed  PubMed Central  Google Scholar 

  15. Lawrence BJ, Gasson N, Loftus AM (2016) Prevalence and subtypes of mild cognitive impairment in Parkinson’s disease. Sci Rep 6:33929. https://doi.org/10.1038/srep33929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Pedersen KF, Larsen JP, Tysnes OB, Alves G (2017) Natural course of mild cognitive impairment in Parkinson disease: a 5-year population-based study. Neurology 88:767–774. https://doi.org/10.1212/WNL.0000000000003634

    Article  PubMed  Google Scholar 

  17. Litvan I, Aarsland D, Adler CH et al (2011) MDS task force on mild cognitive impairment in Parkinson’s disease: critical review of PD-MCI. Mov Disord 26:1814–1824. https://doi.org/10.1002/mds.23823

    Article  PubMed  PubMed Central  Google Scholar 

  18. Dubois B, Burn D, Goetz C et al (2007) Diagnostic procedures for Parkinson’s disease dementia: recommendations from the movement disorder society task force. Mov Disord 22:2314–2324

    Article  PubMed  Google Scholar 

  19. Galasko D (2017) Lewy body disorders. Neurol Clin 35:325–338. https://doi.org/10.1016/j.ncl.2017.01.004

    Article  PubMed  Google Scholar 

  20. Bjornestad A, Pedersen KF, Tysnes OB, Alves G (2017) Clinical milestones in Parkinson’s disease: a 7-year population-based incident cohort study. Parkinsonism Relat Disord. https://doi.org/10.1016/j.parkreldis.2017.05.025

  21. Liu G, Locascio JJ, Corvol JC et al (2017) Prediction of cognition in Parkinson’s disease with a clinical-genetic score: a longitudinal analysis of nine cohorts. Lancet Neurol. https://doi.org/10.1016/S1474-4422(17)30122-9

  22. Chung SJ, Shin JH, Cho KH, Lee Y, Sohn YH, Seong JK, Lee PH (2017) Subcortical shape analysis of progressive mild cognitive impairment in Parkinson’s disease. Mov Disord. https://doi.org/10.1002/mds.27106

  23. Schrag A, Siddiqui UF, Anastasiou Z, Weintraub D, Schott JM (2017) Clinical variables and biomarkers in prediction of cognitive impairment in patients with newly diagnosed Parkinson’s disease: a cohort study. Lancet Neurol 16:66–75. https://doi.org/10.1016/S1474-4422(16)30328-3

    Article  CAS  PubMed  Google Scholar 

  24. Kehagia AA, Barker RA, Robbins TW (2013) Cognitive impairment in Parkinson’s disease: the dual syndrome hypothesis. Neurodegener Dis 11:79–92. https://doi.org/10.1159/000341998

    Article  PubMed  Google Scholar 

  25. Baba T, Hosokai Y, Nishio Y et al (2017) Longitudinal study of cognitive and cerebral metabolic changes in Parkinson’s disease. J Neurol Sci 372:288–293. https://doi.org/10.1016/j.jns.2016.11.068

    Article  CAS  PubMed  Google Scholar 

  26. Trojano L, Papagno C (2017) Cognitive and behavioural disorders in Parkinson’s disease: an update. II: behavioural disorders. Neurol Sci Submitted

  27. Dirnberger G, Jahanshahi M (2013) Executive dysfunction in Parkinson’s disease: a review. J Neuropsychol 7:193–224. https://doi.org/10.1111/jnp.12028

    Article  PubMed  Google Scholar 

  28. Kudlicka A, Clare L, Hindle JV (2011) Executive functions in Parkinson’s disease: systematic review and meta-analysis. Mov Disord 26:2305–2315. https://doi.org/10.1002/mds.23868

    Article  PubMed  Google Scholar 

  29. Gawrys L, Falkiewicz M, Pilacinski A et al (2014) The neural correlates of specific executive dysfunctions in Parkinson’s disease. Acta Neurobiol Exp (Wars) 74:465–478

    Google Scholar 

  30. Goldman JG, Bledsoe IO, Merkitch D, Dinh V, Bernard B, Stebbins GT (2017) Corpus callosal atrophy and associations with cognitive impairment in Parkinson disease. Neurology 88:1265–1272. https://doi.org/10.1212/WNL.0000000000003764

    Article  PubMed  Google Scholar 

  31. Kudlicka A, Clare L, Hindle JV (2013) Pattern of executive impairment in mild to moderate Parkinson’s disease. Dement Geriatr Cogn Disord 36:50–66. https://doi.org/10.1159/000348355

    Article  PubMed  Google Scholar 

  32. Fallon SJ, Hampshire A, Barker RA, Owen AM (2016) Learning to be inflexible: enhanced attentional biases in Parkinson’s disease. Cortex 82:24–34. https://doi.org/10.1016/j.cortex.2016.05.005

    Article  PubMed  Google Scholar 

  33. Gruszka A, Hampshire A, Barker RA, Owen AM (2017) Normal aging and Parkinson’s disease are associated with the functional decline of distinct frontal-striatal circuits. Cortex 93:178–192. https://doi.org/10.1016/j.cortex.2017.05.020

    Article  PubMed  PubMed Central  Google Scholar 

  34. Uitvlugt MG, Pleskac TJ, Ravizza SM (2016) The nature of working memory gating in Parkinson’s disease: a multi-domain signal detection examination. Cogn Affect Behav Neurosci 16:289–301. https://doi.org/10.3758/s13415-015-0389-9

    Article  PubMed  Google Scholar 

  35. Evens R, Hoefler M, Biber K, Lueken U (2016) The Iowa Gambling Task in Parkinson’s disease: a meta-analysis on effects of disease and medication. Neuropsychologia 91:163–172. https://doi.org/10.1016/j.neuropsychologia.2016.07.032

    Article  PubMed  Google Scholar 

  36. Trujillo JP, Gerrits NJ, Veltman DJ, Berendse HW, van der Werf YD, van den Heuvel OA (2015) Reduced neural connectivity but increased task-related activity during working memory in de novo Parkinson patients. Hum Brain Mapp 36(4):1554–1566. https://doi.org/10.1002/hbm.22723

    Article  PubMed  Google Scholar 

  37. Fallon SJ, Smulders K, Esselink RA, van de Warrenburg BP, Bloem BR, Cools R (2015) Differential optimal dopamine levels for set-shifting and working memory in Parkinson’s disease. Neuropsychologia 77:42–51. https://doi.org/10.1016/j.neuropsychologia.2015.07.031

    Article  PubMed  Google Scholar 

  38. Poston KL, YorkWilliams S, Zhang K, Cai W, Everling D, Tayim FM, Llanes S, Menon V (2016) Compensatory neural mechanisms in cognitively unimpaired Parkinson disease. Ann Neurol 79:448–463. https://doi.org/10.1002/ana.24585

    Article  PubMed  PubMed Central  Google Scholar 

  39. Barnish MS, Horton SM, Butterfint ZR, Clark AB, Atkinson RA, Deane KH (2017) Speech and communication in Parkinson’s disease: a cross-sectional exploratory study in the UK. BMJ Open 7:e014642

    Article  PubMed  PubMed Central  Google Scholar 

  40. Cotelli M, Borroni B, Manenti R, Zanetti M, Arévalo A, Cappa SF, Padovani A (2007) Action and object naming in Parkinson’s disease without dementia. Eur J Neurol 14:632–637

    Article  CAS  PubMed  Google Scholar 

  41. Rodrigues IT, Ferreira JJ, Coelho M, Rosa MM, Castro-Caldas A (2015) Action verbal fluency in Parkinson’s patients. Arq Neuropsiquiatr 73:520–525. https://doi.org/10.1590/0004-282X20150056

    Article  PubMed  Google Scholar 

  42. Fernandino L, Conant LL, Binder JR et al (2013) Parkinson’s disease disrupts both automatic and controlled processing of action verbs. Brain Lang 127:65–74

    Article  PubMed  Google Scholar 

  43. Bocanegra Y, García AM, Pineda D et al (2015) Syntax, action verbs, action semantics, and object semantics in Parkinson’s disease: dissociability, progression, and executive influences. Cortex 69:237–254

    Article  PubMed  Google Scholar 

  44. Friederici A (2003) Syntactic comprehension in Parkinson’s disease: investigating early automatic and late integrational processes using event-related brain potentials. Neuropsychology 17:133–142

    Article  PubMed  Google Scholar 

  45. Salmazo-Silva H, de Mattos Pimenta Parente MA, Rocha MS, Roque Baradel R, Cravo AM, Sato JR, Godinho F, Carthery-Goulart MT (2017) Lexical-retrieval and semantic memory in Parkinson’s disease: the question of noun and verb dissociation. Brain Lang 163:10–20

    Article  Google Scholar 

  46. Henry JD, Crawford JR (2004) Verbal fluency deficits in Parkinson’s disease: a meta-analysis. J Int Neuropsychol Soc 10:608–622. https://doi.org/10.1017/S1355617704104141

    Article  PubMed  Google Scholar 

  47. Speed LJ, van Dam WO, Hirath P, Vigliocco G, Desai RH (2017) Impaired comprehension of speed verbs in Parkinson’s disease. J Int Neuropsychol Soc 23:412–420

    Article  PubMed  Google Scholar 

  48. Papagno C, Romero Lauro LJ (2010) The neural basis of idiom processing: neuropsychological, neurophysiological and neuroimaging evidence. Ital J Linguistics 22:21–40

    Google Scholar 

  49. Papagno C, Mattavelli G, Cattaneo Z, Romito L, Albanese A (2014) Ambiguous idiom processing in PD patients. Cogn Neuropsychol 30:495–506

    Article  Google Scholar 

  50. Monetta L, Grindrod CM, Pell MD (2009) Irony comprehension and theory of mind deficits in patients with Parkinson’s disease. Cortex 45:972–981

    Article  PubMed  Google Scholar 

  51. Dubois B, Pillon B (1997) Cognitive deficits in Parkinson’s disease. J Neurol 244:2–8

    Article  CAS  PubMed  Google Scholar 

  52. Trojano L, Gainotti G (2016) Drawing disorders in Alzheimer’s disease and other forms of dementia. J Alzheimers Dis 53:31–52. https://doi.org/10.3233/JAD-160009

    Article  PubMed  Google Scholar 

  53. De Lucia N, Grossi D, Mauro A, Trojano L (2015) Closing-in in Parkinson’s disease individuals with dementia: an experimental study. J Clin Exp Neuropsychol 37:946–955. https://doi.org/10.1080/13803395.2015.1071339

    Article  PubMed  Google Scholar 

  54. De Lucia N, Trojano L, Vitale C, Grossi D, Barone P, Santangelo G (2015) The closing-in phenomenon in Parkinson’s disease. Parkinsonism Relat Disord 21:793–796. https://doi.org/10.1016/j.parkreldis.2015.04.013

    Article  PubMed  Google Scholar 

  55. Seichepine DR, Neargarder S, Davidsdottir S, Reynolds GO, Cronin-Golomb A (2015) Side and type of initial motor symptom influences visuospatial functioning in Parkinson’s disease. J Parkinsons Dis 5:75–83. https://doi.org/10.3233/JPD-140365

    PubMed  PubMed Central  Google Scholar 

  56. Mata IF, Johnson CO, Leverenz JB et al (2017) Large-scale exploratory genetic analysis of cognitive impairment in Parkinson’s disease. Neurobiol Aging 56:211.e1–211.e7. https://doi.org/10.1016/j.neurobiolaging.2017.04.009

    Article  Google Scholar 

  57. Mills KA, Mari Z, Pontone GM et al (2016) Cognitive impairment in Parkinson’s disease: association between patient-reported and clinically measured outcomes. Parkinsonism Relat Disord 33:107–114. https://doi.org/10.1016/j.parkreldis.2016.09.025

    Article  PubMed  PubMed Central  Google Scholar 

  58. Santangelo G, Vitale C, Picillo M et al (2015) Mild cognitive impairment in newly diagnosed Parkinson’s disease: a longitudinal prospective study. Parkinsonism Relat Disord 21:1219–1226. https://doi.org/10.1016/j.parkreldis.2015.08.024

    Article  PubMed  Google Scholar 

  59. Pereira JB, Junqué C, Martí MJ, Ramirez-Ruiz B, Bargalló N, Tolosa E (2009) Neuroanatomical substrate of visuospatial and visuoperceptual impairment in Parkinson’s disease. Mov Disord 24:1193–1199. https://doi.org/10.1002/mds.22560

    Article  PubMed  Google Scholar 

  60. Schneider CB, Linse K, Schönfeld R, Brown S, Koch R, Reichmann H, Leplow B, Storch A (2017) Spatial learning deficits in Parkinson’s disease with and without mild cognitive impairment. Parkinsonism Relat Disord 36:83–88. https://doi.org/10.1016/j.parkreldis.2016.12.020

    Article  PubMed  Google Scholar 

  61. Thurm F, Schuck NW, Fauser M et al (2016) Dopamine modulation of spatial navigation memory in Parkinson’s disease. Neurobiol Aging 38:93–103. https://doi.org/10.1016/j.neurobiolaging.2015.10.019

    Article  CAS  PubMed  Google Scholar 

  62. Calabresi P, Castrioto A, Di Filippo M, Picconi B (2013) New experimental and clinical links between the hippocampus and the dopaminergic system in Parkinson’s disease. Lancet Neurol 12:811–821. https://doi.org/10.1016/S1474-4422(13)70118-2

    Article  CAS  PubMed  Google Scholar 

  63. Massman PJ, Delis DC, Butters N, Levin BE, Salmon DP (1990) Are all subcortical dementias alike? Verbal learning and memory in Parkinson’s and Huntington’s disease patients. J Clin Exp Neuropsychol 12:729–744

    Article  CAS  PubMed  Google Scholar 

  64. Pirogovsky-Turk E, Filoteo VJ, Litvan I, Harrington DL (2015) Structural MRI correlates of episodic memory processes in Parkinson’s disease without mild cognitive impairment. J Parkinsons Dis 5:971–981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Beyer MK, Bronnick KS, Hwang KS et al (2013) Verbal memory is associated with structural hippocampal changes in newly diagnosed Parkinson’s disease. J Neurol Neurosurg Psychiatry 84:23–28

    Article  PubMed  Google Scholar 

  66. Costa A, Monaco M, Zabberoni S et al (2014) Free and cued recall memory in Parkinson’s disease associated with amnestic mild cognitive impairment. PLoS One 9(1):e86233. https://doi.org/10.1371/journal.pone.0086233

    Article  PubMed  PubMed Central  Google Scholar 

  67. Cohn M, Giannolys I, De Belder M, Saint-Cyr JA, McAndrews MP (2016) Associative reinstatement memory measures hippocampal function in Parkinson’s disease. Neuropsychologia 90:25–32

    Article  PubMed  Google Scholar 

  68. Williams-Gray CH, Mason SL, Evans JR, Foltynie T, Brayne C, Robbins TW, Barker RA (2013) The CamPaIGN study of Parkinson’s disease: 10-year outlook in an incident population-based cohort. J Neurol Neurosurg Psychiatry 84:1258–1264

    Article  PubMed  Google Scholar 

  69. Santangelo G, Siciliano M, Pedone R et al (2015) Normative data for the Montreal Cognitive Assessment in an Italian population sample. Neurol Sci 36:585–591. https://doi.org/10.1007/s10072-014-1995-y

    Article  PubMed  Google Scholar 

  70. Santangelo G, Barone P, Abbruzzese G et al (2014) Validation of the Italian version of Parkinson’s disease-cognitive rating scale (PD-CRS). Neurol Sci 35:537–544. https://doi.org/10.1007/s10072-013-1538-y

    Article  PubMed  Google Scholar 

  71. Isella V, Mapelli C, Morielli N et al (2013) Psychometric properties of the Italian version of the Scales for Outcomes in Parkinson’s disease-Cognition (SCOPA-Cog). Funct Neurol 28:121–125

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Nazem S, Siderowf AD, Duda JE et al (2009) Montreal cognitive assessment performance in patients with Parkinson’s disease with ‘normal’ global cognition according to Mini-Mental State Examination Score. J Am Geriatr Soc 57:304–308

    Article  PubMed  Google Scholar 

  73. Fengler S, Kessler J, Timmermann L, Zapf A, Elben S, Wojtecki L, Tucha O, Kalbe E (2016) Screening for cognitive impairment in Parkinson’s disease: improving the diagnostic utility of the MoCA through subtest weighting. PLoS One 11:e0159318. https://doi.org/10.1371/journal.pone.0159318

    Article  PubMed  PubMed Central  Google Scholar 

  74. Dujardin K, Auzou N, Lhomméee E et al (2016) French consensus procedure for assessing cognitive function in Parkinson’s disease. Revue Neurol (Paris) 172:696–702

    Article  CAS  Google Scholar 

  75. Hoogland J, Boel JA, DeBie RMA, Geskus RB, Schmand BA, Dalrympe-Alford JC, Marras C, Adler CH, Goldman JG, et al. on behalf of th MDS Study Group Validation of Mild Cognitive Impairment in Parkinson Disease (2017) Mild cognitive impairment as a risk factor for Parkinson’s disease dementia. Mov Disord 32. Doi: https://doi.org/10.1002/mds.27002

  76. Goldman JG, Holdan S, Bernard B, Ouyang B, Goetz CG, Stebbins GT (2013) Defining optimal cutoff scores for cognitive impairment using Movement Disorder Society Task Force criteria for mild cognitive impairment in Parkinson’s disease. Mov Disord 28:1972–1979

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. CIMeC, University of Trento, Trento, Italy

    Costanza Papagno

  2. Department of Psychology, University of Milano-Bicocca, Piazza dell’Ateneo 1, 02100, Milan, Italy

    Costanza Papagno

  3. Department of Psychology, University of Campania ‘Luigi Vanvitelli’, Viale Ellittico 31, 81100, Caserta, Italy

    Luigi Trojano

  4. ICS Maugeri, IRCCS, Telese Terme, Italy

    Luigi Trojano

Authors
  1. Costanza Papagno
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luigi Trojano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Costanza Papagno or Luigi Trojano.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Papagno, C., Trojano, L. Cognitive and behavioral disorders in Parkinson’s disease: an update. I: cognitive impairments. Neurol Sci 39, 215–223 (2018). https://doi.org/10.1007/s10072-017-3154-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-017-3154-8

Keywords

Search

Navigation