Identifying subtypes of mild cognitive impairment in Parkinson’s disease using cluster analysis

Abstract

Introduction

The concept of Mild Cognitive Impairment (MCI) in Parkinson’s disease (PD) has shown the potential for identifying at-risk dementia patients. Identifying subtypes of MCI is likely to assist therapeutic discoveries and better clinical management of patients with PD (PWP). Recent cluster-based approaches have demonstrated dominance in memory and executive impairment in PD. The present study will further explore the role of memory and executive impairment and associated clinical features in non-demented PWP.

Method

A K-means cluster analysis was performed on ten “frontal” and “posterior” cognitive variables derived from a dataset of 85 non-demented PWP. The resulting cluster structure was chosen based on quantitative, qualitative, theoretical, and clinical validity. Cluster profiles were then created through statistical analysis of cognitive and clinical/demographic variables. A descriptive analysis of each cluster’s performance on a comprehensive PD-MCI diagnostic battery was also explored.

Results

The resulting cluster structure revealed four distinct cognitive phenotypes: (1) frontal-dominant impairment; (2) posterior-cortical-dominant impairment; (3) global impairment, and (4) cognitively intact. Demographic profiling revealed significant differences in the age, gender split, global cognitive ability, and motor symptoms between these clusters. However, there were no significant differences between the clusters on measures of depression, apathy, and anxiety.

Conclusion

These results validate the existence of distinct cognitive phenotypes within PD-MCI and encourage future research into their clinical trajectory and neuroimaging correlates.

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

Fig. 1
Fig. 2

References

  1. 1.

    Hobson P, Meara J (2015) Mild cognitive impairment in Parkinson's disease and its progression onto dementia: a 16-year outcome evaluation of the Denbighshire cohort. Int J Geriatr Psychiatr 30(10):1048–1055. https://doi.org/10.1002/gps.4261

    Article  Google Scholar 

  2. 2.

    Biundo R, Weis L, Antonini A (2016) Cognitive decline in Parkinson’s disease: the complex picture. NPJ Parkinsons Dis 2:16018. https://doi.org/10.1038/npjparkd.2016.18

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Goldman JG, Williams-Gray C, Barker RA, Duda JE, Galvin JE (2014) The spectrum of cognitive impairment in Lewy body diseases. Mov Disord 29(5):608–621. https://doi.org/10.1002/mds.25866

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Kehagia AA, Barker RA, Robbins TW (2012) Cognitive impairment in Parkinson’s disease: the dual syndrome hypothesis. Neurodegener Dis 11(2):79–92. https://doi.org/10.1159/000341998

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Foltynie T, Brayne C, Robbins T, Barker R (2004) The cognitive ability of an incident cohort of Parkinson's patients in the UK. The CamPaIGN study. Brain 127(3):550–560. https://doi.org/10.1093/brain/awh067

    Article  PubMed  Google Scholar 

  6. 6.

    Miller IN, Neargarder S, Risi MM, Cronin-Golomb A (2013) Frontal and posterior subtypes of neuropsychological deficit in Parkinson's disease. Behav Neurosci 127(2):175–183. https://doi.org/10.1037/a0031357

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Dujardin K, Leentjens AFG, Langlois C, Moonen AJH, Duits AA, Carette AS, Duhamel A (2013) The spectrum of cognitive disorders in Parkinson's disease: a data-driven approach. Mov Disord 28(2):183–189. https://doi.org/10.1002/mds.25311

    Article  PubMed  Google Scholar 

  8. 8.

    Dujardin K, Moonen AJH, Behal H, Defebvre L, Duhamel A, Duits AA, Plomhause L, Tard C, Leentjens AFG (2015) Cognitive disorders in Parkinson's disease: confirmation of a spectrum of severity. Parkinsonism Relat Disord 21(11):1299–1305. https://doi.org/10.1016/j.parkreldis.2015.08.032

    Article  PubMed  Google Scholar 

  9. 9.

    Fraiman R, Justel A, Svarc M (2008) Selection of variables for cluster analysis and classification rules. J Am Stat Assoc 103(483):1294–1303. https://doi.org/10.1198/016214508000000544

    CAS  Article  Google Scholar 

  10. 10.

    Alonso-Recio L, Martín-Plasencia P, Ruiz M, Serrano JM (2018) Differences in cognitive performance in nondemented Parkinson’s disease: a latent profile analysis of cognitive subtypes. J Clin Exp Neuropsychol. https://doi.org/10.1080/13803395.2018.1432570

    Article  PubMed  Google Scholar 

  11. 11.

    Gibb WR, Lees AJ (1988) The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. J Neurol Neurosurg Psychiatr 51(6):745. https://doi.org/10.1136/jnnp.51.6.745

    CAS  Article  Google Scholar 

  12. 12.

    Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, Hilten JJV, LaPelle N (2008) Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Scale presentation and clinimetric testing results. Mov Disord 23(15):2129–2170. https://doi.org/10.1002/mds.22340

    Article  PubMed  Google Scholar 

  13. 13.

    Bech P, Coppen A (1990) The Hamilton scales. Springer, Berlin

    Google Scholar 

  14. 14.

    Pedersen FK, Larsen PJ, Tysnes PO-B, Alves PG (2017) Natural course of mild cognitive impairment in Parkinson disease: a 5-year population-based study. Neurology 88(8):767–774. https://doi.org/10.1212/WNL.0000000000003634

    Article  PubMed  Google Scholar 

  15. 15.

    Leentjens AFG, Dujardin K, Pontone GM, Starkstein SE, Weintraub D, Martinez-Martin P (2014) The Parkinson Anxiety Scale (PAS): development and validation of a new anxiety scale. Mov Disord 29(8):1035–1043. https://doi.org/10.1002/mds.25919

    Article  PubMed  Google Scholar 

  16. 16.

    Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE (2010) Systematic review of levodopa dose equivalency reporting in Parkinson's disease. Mov Disord 25(15):2649–2653. https://doi.org/10.1002/mds.23429

    Article  PubMed  Google Scholar 

  17. 17.

    Dalrymple-Alford JC, Macaskill MR, Nakas CT, Livingston L, Graham C, Crucian GP, Melzer TR, Kirwan J, Keenan R, Wells S, Porter RJ, Watts R, Anderson TJ (2010) The MoCA: well-suited screen for cognitive impairment in Parkinson disease. Neurology 75(19):1717–1725. https://doi.org/10.1212/WNL.0b013e3181fc29c9

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Litvan I, Goldman JG, Tröster AI, Schmand BA, Weintraub D, Petersen RC, Mollenhauer B, Adler CH, Marder K, Williams-Gray CH, Aarsland D, Kulisevsky J, Rodriguez-Oroz MC, Burn DJ, Barker RA, Emre M (2012) Diagnostic criteria for mild cognitive impairment in Parkinson's disease: Movement Disorder Society Task Force guidelines. Mov Disord 27(3):349–356. https://doi.org/10.1002/mds.24893

    Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Delis D (2001) Delis Kaplan (D-KEFS) technical manual. San Antonio, TX

  20. 20.

    Benedict RHB, Brandt J (2007) Hopkin’s verbal learning test-revised/brief visuospatial memory test-revised: professional manual supplement. PAR, Lutz

    Google Scholar 

  21. 21.

    Golden CJ, Freshwater SM (2002) STROOP colour and word test: a manual for clinical and experimental uses. Stoelting, Wood Dale

    Google Scholar 

  22. 22.

    Lezak MD (2012) Neuropsychological assessment, 5th edn. Oxford University Press, New York

    Google Scholar 

  23. 23.

    Calamia M, Markon K, Denburg NL, Tranel D (2011) Developing a short form of Benton's judgment of line orientation test: an item response theory approach. Clin Neuropsychol 25(4):670–684. https://doi.org/10.1080/13854046.2011.564209

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Royall DR, Cordes JA, Polk M (1998) CLOX: an executive clock drawing task. J Neurol Neurosurg Psychiatr 64(5):588. https://doi.org/10.1136/jnnp.64.5.588

    CAS  Article  Google Scholar 

  25. 25.

    Kaplan E, Goodglass H, Weintraub S (1983) Boston naming test. Lea & Febiger, Philadelphia

    Google Scholar 

  26. 26.

    Sarstedt M, Mooi E (2014) A concise guide to market research. The process, data, and methods using IBM SPSS statistics. Springer, Berlin. https://doi.org/10.1007/978-3-642-53965-7

    Google Scholar 

  27. 27.

    Ibarretxe-Bilbao N, Junque C, Marti MJ, Tolosa E (2011) Brain structural MRI correlates of cognitive dysfunctions in Parkinson's disease. J Neurol Sci 310(1):70–74. https://doi.org/10.1016/j.jns.2011.07.054

    Article  PubMed  Google Scholar 

  28. 28.

    Schmidt CSM, Nitschke K, Bormann T, Römer P, Kümmerer D, Martin M, Umarova RM, Leonhart R, Egger K, Dressing A, Musso M, Willmes K, Weiller C, Kaller CP (2019) Dissociating frontal and temporal correlates of phonological and semantic fluency in a large sample of left hemisphere stroke patients. Neuroimage Clin 23:101840. https://doi.org/10.1016/j.nicl.2019.101840

    Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Müller LD, Guhn A, Zeller JB, Biehl SC, Dresler T, Hahn T, Fallgatter AJ, Polak T, Deckert J, Herrmann MJ (2014) Neural correlates of a standardized version of the trail making test in young and elderly adults: a functional near-infrared spectroscopy study. Neuropsychologia 56:271–279. https://doi.org/10.1016/j.neuropsychologia.2014.01.019

    Article  PubMed  Google Scholar 

  30. 30.

    Owen AM, Lee ACH, Williams EJ (2000) Dissociating aspects of verbal working memory within the human frontal lobe: further evidence for a “process-specific” model of lateral frontal organization. Psychobiology 28(2):146–155. https://doi.org/10.3758/BF03331974

    Article  Google Scholar 

  31. 31.

    Pagonabarraga J, Kulisevsky J, Llebaria G, García-Sánchez C, Pascual-Sedano B, Gironell A (2008) Parkinson's disease-cognitive rating scale: a new cognitive scale specific for Parkinson's disease. Mov Disord 23(7):998–1005. https://doi.org/10.1002/mds.22007

    Article  PubMed  Google Scholar 

  32. 32.

    Malika C, Nadia G, Véronique B, Azam N (2014) NbClust: an R package for determining the relevant number of clusters in a data set. J Stat Softw 61(1):1–36. https://doi.org/10.18637/jss.v061.i06

    Article  Google Scholar 

  33. 33.

    Maechler M, Rousseeuw P, Struyf A, Hubert M, Hornik K (2018) Cluster: cluster analysis basics and extensions. R package v2.0.7-1

  34. 34.

    Palavra NC, Naismith SL, Lewis SJG (2013) Mild cognitive impairment in Parkinson's disease: a review of current concepts. Neurol Res Int 2013:8. https://doi.org/10.1155/2013/576091

    Article  Google Scholar 

  35. 35.

    Sachdev P, Blacker D, Blazer D, Ganguli M, V Jeste D, Paulsen J, Petersen R (2014) Classifying neurocognitive disorders: the DSM-5 approach, vol 10. https://doi.org/10.1038/nrneurol.2014.181

  36. 36.

    Koerts J, Meijer H, Colman K, Tucha L, Lange K, Tucha O (2013) What is measured with verbal fluency tests in Parkinson’s disease patients at different stages of the disease? J Neural Transm 120(3):403–411. https://doi.org/10.1007/s00702-012-0885-9

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the Royal Brisbane and Woman’s Foundation for Grant funding, and all participants of the study. Dr. Nadeeka is supported by the Lions Medical Research Foundation Fellowship and National Health and Medical Research Boosting Dementia Research Leadership Fellowship (APP1137339).

Funding

This work was supported by the Royal Brisbane and Woman’s Hospital Foundation and Lions Medical Research Foundation.

Author information

Affiliations

Authors

Contributions

DP—conceptualization, design of study, data analysis, writing of the first draft, and revision of subsequent drafts. JJY—conceptualization, design of the test battery, data collection, critical revision. GJB—design of the test battery, supervision, financial support, and critical revision. JDO—recruitment of participants and critical revision. LM—design of the test battery. KLM—design of the test battery, student supervision, and critical revision. DAC—design of the test battery, student supervision, and critical revision. NND—conceptualization, design of study, design of the test battery, student supervision, and critical revision of subsequent drafts.

Corresponding author

Correspondence to Nadeeka N. Dissanayaka.

Ethics declarations

Conflicts of interest

The authors declare that there was no potential conflict of interest.

Ethical standard statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Availability of data and material (data transparency)

Available upon request.

Code availability (software application or custom code)

Available upon request.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Pourzinal, D., Yang, J.H.J., Byrne, G.J. et al. Identifying subtypes of mild cognitive impairment in Parkinson’s disease using cluster analysis. J Neurol (2020). https://doi.org/10.1007/s00415-020-09977-z

Download citation

Keywords

  • Parkinson’s disease
  • Mild cognitive impairment
  • Cluster analysis