Neurological Sciences

, Volume 39, Issue 2, pp 215–223 | Cite as

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

  • Costanza PapagnoEmail author
  • Luigi TrojanoEmail author
Review Article


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.


Parkinson’s disease Cognitive impairment Dementia Fronto-striatal pathways Executive functions 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Schapira AHV, Chaudhuri KR, Jenner P (2017) Non-motor features of Parkinson disease. Nat Rev Neurosci.
  2. 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 12:35–41CrossRefGoogle Scholar
  3. 3.
    Marras C, Chaudhuri KR (2016) Nonmotor features of Parkinson’s disease subtypes. Mov Disord 31:1095–1102CrossRefPubMedGoogle Scholar
  4. 4.
    Przedborski S (2017) The two-century journey of Parkinson disease research. Nat Rev Neurosci 18:251–259. CrossRefPubMedGoogle Scholar
  5. 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. CrossRefPubMedGoogle Scholar
  6. 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. CrossRefPubMedGoogle Scholar
  7. 7.
    DeLong MR (1990) Primate models of movement disorders of basal ganglia origin. Trends Neurosci 13:281–285CrossRefPubMedGoogle Scholar
  8. 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. CrossRefPubMedGoogle Scholar
  9. 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. CrossRefPubMedGoogle Scholar
  10. 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 8:275CrossRefPubMedPubMedCentralGoogle Scholar
  11. 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 16:351–359CrossRefPubMedGoogle Scholar
  12. 12.
    Ye Z, Altena E, Nombela C et al (2015) Selective serotonin reuptake inhibition modulates response inhibition in Parkinson’s disease. Brain 137:1145–1155CrossRefGoogle Scholar
  13. 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 60:1745–1748CrossRefPubMedGoogle Scholar
  14. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Lawrence BJ, Gasson N, Loftus AM (2016) Prevalence and subtypes of mild cognitive impairment in Parkinson’s disease. Sci Rep 6:33929. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 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. CrossRefPubMedGoogle Scholar
  17. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 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 22:2314–2324CrossRefPubMedGoogle Scholar
  19. 19.
    Galasko D (2017) Lewy body disorders. Neurol Clin 35:325–338. CrossRefPubMedGoogle Scholar
  20. 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.
  21. 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.
  22. 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.
  23. 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. CrossRefPubMedGoogle Scholar
  24. 24.
    Kehagia AA, Barker RA, Robbins TW (2013) Cognitive impairment in Parkinson’s disease: the dual syndrome hypothesis. Neurodegener Dis 11:79–92. CrossRefPubMedGoogle Scholar
  25. 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. CrossRefPubMedGoogle Scholar
  26. 26.
    Trojano L, Papagno C (2017) Cognitive and behavioural disorders in Parkinson’s disease: an update. II: behavioural disorders. Neurol Sci SubmittedGoogle Scholar
  27. 27.
    Dirnberger G, Jahanshahi M (2013) Executive dysfunction in Parkinson’s disease: a review. J Neuropsychol 7:193–224. CrossRefPubMedGoogle Scholar
  28. 28.
    Kudlicka A, Clare L, Hindle JV (2011) Executive functions in Parkinson’s disease: systematic review and meta-analysis. Mov Disord 26:2305–2315. CrossRefPubMedGoogle Scholar
  29. 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) 74:465–478Google Scholar
  30. 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. CrossRefPubMedGoogle Scholar
  31. 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. CrossRefPubMedGoogle Scholar
  32. 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. CrossRefPubMedGoogle Scholar
  33. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  34. 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. CrossRefPubMedGoogle Scholar
  35. 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. CrossRefPubMedGoogle Scholar
  36. 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. CrossRefPubMedGoogle Scholar
  37. 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. CrossRefPubMedGoogle Scholar
  38. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  39. 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:e014642CrossRefPubMedPubMedCentralGoogle Scholar
  40. 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 14:632–637CrossRefPubMedGoogle Scholar
  41. 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. CrossRefPubMedGoogle Scholar
  42. 42.
    Fernandino L, Conant LL, Binder JR et al (2013) Parkinson’s disease disrupts both automatic and controlled processing of action verbs. Brain Lang 127:65–74CrossRefPubMedGoogle Scholar
  43. 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 69:237–254CrossRefPubMedGoogle Scholar
  44. 44.
    Friederici A (2003) Syntactic comprehension in Parkinson’s disease: investigating early automatic and late integrational processes using event-related brain potentials. Neuropsychology 17:133–142CrossRefPubMedGoogle Scholar
  45. 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 163:10–20CrossRefGoogle Scholar
  46. 46.
    Henry JD, Crawford JR (2004) Verbal fluency deficits in Parkinson’s disease: a meta-analysis. J Int Neuropsychol Soc 10:608–622. CrossRefPubMedGoogle Scholar
  47. 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 23:412–420CrossRefPubMedGoogle Scholar
  48. 48.
    Papagno C, Romero Lauro LJ (2010) The neural basis of idiom processing: neuropsychological, neurophysiological and neuroimaging evidence. Ital J Linguistics 22:21–40Google Scholar
  49. 49.
    Papagno C, Mattavelli G, Cattaneo Z, Romito L, Albanese A (2014) Ambiguous idiom processing in PD patients. Cogn Neuropsychol 30:495–506CrossRefGoogle Scholar
  50. 50.
    Monetta L, Grindrod CM, Pell MD (2009) Irony comprehension and theory of mind deficits in patients with Parkinson’s disease. Cortex 45:972–981CrossRefPubMedGoogle Scholar
  51. 51.
    Dubois B, Pillon B (1997) Cognitive deficits in Parkinson’s disease. J Neurol 244:2–8CrossRefPubMedGoogle Scholar
  52. 52.
    Trojano L, Gainotti G (2016) Drawing disorders in Alzheimer’s disease and other forms of dementia. J Alzheimers Dis 53:31–52. CrossRefPubMedGoogle Scholar
  53. 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. CrossRefPubMedGoogle Scholar
  54. 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. CrossRefPubMedGoogle Scholar
  55. 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. PubMedPubMedCentralGoogle Scholar
  56. 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. CrossRefGoogle Scholar
  57. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  58. 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. CrossRefPubMedGoogle Scholar
  59. 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. CrossRefPubMedGoogle Scholar
  60. 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. CrossRefPubMedGoogle Scholar
  61. 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. CrossRefPubMedGoogle Scholar
  62. 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. CrossRefPubMedGoogle Scholar
  63. 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 12:729–744CrossRefPubMedGoogle Scholar
  64. 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 5:971–981CrossRefPubMedPubMedCentralGoogle Scholar
  65. 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 84:23–28CrossRefPubMedGoogle Scholar
  66. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  67. 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 90:25–32CrossRefPubMedGoogle Scholar
  68. 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 84:1258–1264CrossRefPubMedGoogle Scholar
  69. 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. CrossRefPubMedGoogle Scholar
  70. 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. CrossRefPubMedGoogle Scholar
  71. 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 28:121–125PubMedPubMedCentralGoogle Scholar
  72. 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 57:304–308CrossRefPubMedGoogle Scholar
  73. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Dujardin K, Auzou N, Lhomméee E et al (2016) French consensus procedure for assessing cognitive function in Parkinson’s disease. Revue Neurol (Paris) 172:696–702CrossRefGoogle Scholar
  75. 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:
  76. 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 28:1972–1979CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Italia S.r.l. 2017

Authors and Affiliations

  1. 1.CIMeCUniversity of TrentoTrentoItaly
  2. 2.Department of PsychologyUniversity of Milano-BicoccaMilanItaly
  3. 3.Department of PsychologyUniversity of Campania ‘Luigi Vanvitelli’CasertaItaly
  4. 4.ICS MaugeriIRCCSTelese TermeItaly

Personalised recommendations