Journal of Neurology

, Volume 262, Issue 2, pp 425–434 | Cite as

Resting-state functional connectivity associated with mild cognitive impairment in Parkinson’s disease

  • Marianna Amboni
  • Alessandro Tessitore
  • Fabrizio Esposito
  • Gabriella Santangelo
  • Marina Picillo
  • Carmine Vitale
  • Alfonso Giordano
  • Roberto Erro
  • Rosa de Micco
  • Daniele Corbo
  • Gioacchino Tedeschi
  • Paolo Barone
Original Communication

Abstract

Cognitive impairment is common in PD, even in early stages. The construct of mild cognitive impairment has been used to identify clinically evident cognitive impairment without functional decline in PD patients (PD-MCI). The aim of the present study was to investigate brain connectivity associated with PD-MCI through RS-fMRI. RS-fMRI at 3T was collected in 42 PD patients and 20 matched healthy controls. Among PD patients, 21 were classified as having MCI (PD-MCI) and 21 as cognitively unimpaired (PD-nMCI) based on criteria for possible PD-MCI (level I category). Single-subject and group-level ICA was used to investigate the integrity of brain networks related to cognition in PD patients with and without MCI. Image data processing and statistical analysis were performed in BrainVoyager QX. In addition, we used VBM to test whether functional connectivity differences were related to structural abnormalities. PD-nMCI and PD-MCI patients compared with controls showed decreased DMN connectivity. PD-MCI patients, but not PD-nMCI, compared with controls, showed decreased functional connectivity of bilateral prefrontal cortex within the frontoparietal network. The decreased prefrontal cortex connectivity correlated with cognitive parameters but not with clinical variables. VBM analysis did not reveal any difference in local gray matter between patients and controls. Our findings suggest that an altered DMN connectivity characterizes PD patients, regardless of cognitive status, whereas a functional disconnection of the frontoparietal network could be associated with MCI in PD in the absence of detectable structural changes.

Keywords

Movement disorders Parkinson’s disease Cognitive disorders and dementia Mild cognitive impairment fMRI Imaging 

Notes

Acknowledgments

We thank Dr. Alessandro Iavarone for his precious statistical contribution.

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical standard

All participants provided written informed consent to the protocol that has been performed in accordance with the Declaration of Helsinki and approved by the local Ethics Committee.

References

  1. 1.
    Muslimovic D, Post B, Speelman JD, Schmand B (2005) Cognitive profile of patients with newly diagnosed Parkinson disease. Neurology 65:1239–1245CrossRefPubMedGoogle Scholar
  2. 2.
    Barone P, Aarsland D, Burn D, Emre M, Kulisevsky J, Weintraub D (2011) Cognitive impairment in nondemented Parkinson’s disease. Mov Disord 26:2483–2495CrossRefPubMedGoogle Scholar
  3. 3.
    Caviness JN, Driver-Dunckley E, Connor DJ et al (2007) Defining mild cognitive impairment in Parkinson’s disease. Mov Disord 22:1272–1277CrossRefPubMedGoogle Scholar
  4. 4.
    Litvan I, Goldman JG, Troster AI et al (2012) Diagnostic criteria for mild cognitive impairment in Parkinson’s disease: movement disorder society task force guidelines. Mov Disord 27:349–356PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Broeders M, de Bie RMA, Velseboer DC, Speelman JD, Muslimovic D, Schmand B (2013) Evolution of mild cognitive impairment in Parkinson disease. Neurology 81:1–7CrossRefGoogle Scholar
  6. 6.
    Aarsland D, Larsen JP, Tandberg E, Laake K (2000) Predictors of nursing home placement in Parkinson’s disease: a population-based, prospective study. J Am Geriatr Soc 48:938–942CrossRefPubMedGoogle Scholar
  7. 7.
    Levy G, Tang MX, Louis ED et al (2002) The association of incident dementia with mortality in PD. Neurology 59:1708–1713CrossRefPubMedGoogle Scholar
  8. 8.
    Beyer MK, Janvin CC, Larsen JP, Aarsland D (2007) A magnetic resonance imaging study of patients with Parkinson’s disease with mild cognitive impairment and dementia using voxel-based morphometry. J Neurol Neurosurg Psychiatry 78:254–259PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Song SK, Lee JE, Park H-J, Sohn YH, Lee JD, Lee PH (2011) The pattern of cortical atrophy in patients with Parkinson’s disease according to cognitive status. Mov Disord 26:289–296CrossRefPubMedGoogle Scholar
  10. 10.
    Weintraub D, Doshi J, Koka D et al (2011) Neurodegeneration across stages of cognitive decline in Parkinson disease. Arch Neurol 68:1562–1568PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Melzer TR, Watts R, MacAskill MR et al (2012) Grey matter atrophy in cognitively impaired Parkinson’s disease. J Neurol Neurosurg Psychiatry 83:188–194CrossRefPubMedGoogle Scholar
  12. 12.
    Lyoo CH, Jeong Y, Ryu YH, Rinne JO, Lee MS (2010) Cerebral glucose metabolism of Parkinson’s disease patients with mild cognitive impairment. Eur Neurol 64:65–73CrossRefPubMedGoogle Scholar
  13. 13.
    Huang C, Mattis P, Perrine K, Brown N, Dhawan V, Eidelberg D (2008) Metabolic abnormalities associated with mild cognitive impairment in Parkinson disease. Neurology 70:1470–1477PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Pappatà S, Santangelo G, Aarsland D et al (2011) Mild cognitive impairment in drug-naïve patients with PD is associated with cerebral hypometabolism. Neurology 77:1357–1362CrossRefPubMedGoogle Scholar
  15. 15.
    Damoiseaux JS, Rombouts SA, Barkhof F et al (2006) Consistent resting-state networks across healthy subjects. Proc Natl Acad Sci USA 103:13848–13853PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Esposito F, Aragri A, Pesaresi I et al (2008) Independent component model of the default-mode brain function: combining individual-level and population-level analyses in resting-state fMRI. Magn Reson Imaging 26:905–913CrossRefPubMedGoogle Scholar
  17. 17.
    Filippi M, Agosta F, Scola E et al (2013) Functional network connectivity in the behavioral variant of frontotemporal dementia. Cortex 49(9):2389–2401CrossRefPubMedGoogle Scholar
  18. 18.
    Pievani M, de Haan W, Wu T, Seeley WW, Frisoni GB (2011) Functional network disruption in the degenerative dementias. Lancet Neurol 10(9):829–843PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    van Eimeren T, Monchi O, Ballanger B, Strafella AP (2009) Dysfunction of the default mode network in Parkinson disease: a functional magnetic resonance imaging study. Arch Neurol 66:877–883PubMedCentralPubMedGoogle Scholar
  20. 20.
    Tessitore A, Esposito F, Vitale C et al (2012) Default-mode network connectivity in cognitively unimpaired patients with Parkinson disease. Neurology 79:2226–2232CrossRefPubMedGoogle Scholar
  21. 21.
    Ibarretxe-Bilbao N, Zarei M, Junque C et al (2011) Dysfunctions of cerebral networks precede recognition memory deficits in early Parkinson’s disease. Neuroimage 57(2):589–597CrossRefPubMedGoogle Scholar
  22. 22.
    Seibert TM, Murphy EA, Kaestner EJ, Brewer JB (2012) Interregional correlations in Parkinson disease and Parkinson-related dementia with resting functional MR Imaging. Radiology 263:226–234PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Rektorova I, Krajcovicova L, Marecek R, Mikl M (2012) Default mode network and extrastriate visual resting state network in patients with Parkinson’s disease dementia. Neurodegener Dis 10(1–4):232–237CrossRefPubMedGoogle Scholar
  24. 24.
    Rektorova I, Krajcovicova L, Marecek R, Novakova M, Mikl M (2014) Default mode network connectivity patterns associated with visual processing at different stages of Parkinson’s disease. J Alzheimers Dis 42(Suppl 3):S217–S228PubMedGoogle Scholar
  25. 25.
    Baggio HC, Segura B, Sala-Llonch R et al (2014) Cognitive impairment and resting-state network connectivity in Parkinson’s disease. Hum Brain Mapp. 28 Aug (Epub ahead of print)Google Scholar
  26. 26.
    Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) The accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinicopathological study. J Neurol Neurosurg Psychiatry 55:181–184PubMedCentralCrossRefPubMedGoogle Scholar
  27. 27.
    Emre M, Aarsland D, Brown R et al (2007) Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov Disord 22:1689–1707CrossRefPubMedGoogle Scholar
  28. 28.
    American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatry Association, Washington, DCGoogle Scholar
  29. 29.
    Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E (1999) Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 56:303–308CrossRefPubMedGoogle Scholar
  30. 30.
    Caltagirone C, Gainotti G, Masullo C, Miceli G (1979) Validity of some neuropsychological tests in the assessment of mental deterioration. Acta Psychiatr Scand 60:50–56CrossRefPubMedGoogle Scholar
  31. 31.
    Dubois B, Slachevsky A, Litvan I, Pillon B (2000) The FAB: a frontal assessment battery at bedside. Neurology 55:1621–1626CrossRefPubMedGoogle Scholar
  32. 32.
    Barbarotto R, Laiacona M, Frosio R, Vecchio M, Farinato A, Capitani E (1998) A normative study on visual reaction times and two Stroop colour-word tests. Ital J Neurol Sci 19:161–170CrossRefPubMedGoogle Scholar
  33. 33.
    Spinnler H, Tognoni G (1987) Standardizzazione e taratura italiana di test neuropsicologici. Ital J Neurol Sci 6(8):1–20Google Scholar
  34. 34.
    Caffarra P, Vezzadini G, Dieci F, Zonato F, Venneri A (2002) Rey–Osterrieth complex figure: normative values in an Italian population sample. Neurol Sci 22:443–447CrossRefPubMedGoogle Scholar
  35. 35.
    Mondini S, Mapelli D, Vestri A, Bisiacchi PS (2003) Esame neuropsicologico breve: una batteria di test per lo screening neuropsicologico. Raffaello Cortina Editore, MilanoGoogle Scholar
  36. 36.
    Aarsland D, Bronnick K, Williams-Gray C et al (2010) Mild cognitive impairment in Parkinson disease: a multicenter pooled analysis. Neurology 75:1062–1069PubMedCentralCrossRefPubMedGoogle Scholar
  37. 37.
    Hyvarinen A, Hoyer PO, Inki M (2001) Topographic independent component analysis. Neural Comput 13:1527–1558CrossRefPubMedGoogle Scholar
  38. 38.
    Esposito F, Scarabino T, Hyvarinen A et al (2005) Independent component analysis of fMRI group studies by self-organizing clustering. Neuroimage 25:193–205CrossRefPubMedGoogle Scholar
  39. 39.
    Greicius MD, Flores BH, Menon V et al (2007) Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus. Biol Psychiatry 62:429–437PubMedCentralCrossRefPubMedGoogle Scholar
  40. 40.
    Hyvärinen A, Karhunen J, Oja E (2001) Independent component analysis. Wiley, New YorkCrossRefGoogle Scholar
  41. 41.
    Forman SD, Cohen JD, Fitzgerald M, Eddy WF, Mintun MA, Noll DC (1995) Improved assessment of significant activation in functional magnetic resonance imaging (fMRI): use of a cluster-size threshold. Magn Reson Med 33:636–647CrossRefPubMedGoogle Scholar
  42. 42.
    Ashburner J, Friston KJ (2005) Unified segmentation. Neuroimage 26:839–851CrossRefPubMedGoogle Scholar
  43. 43.
    Foltynie T, Brayne CE, Robbins TW, Barker RA (2004) The cognitive ability of an incident cohort of Parkinson’s patients in the UK. The CamPaIGN study. Brain 127:550–560CrossRefPubMedGoogle Scholar
  44. 44.
    Aarsland D, Bronnick K, Larsen JP, Tysnes OB, Alves G (2009) Cognitive impairment in incident, untreated Parkinson disease: the Norwegian ParkWest study. Neurology 72:1121–1126CrossRefPubMedGoogle Scholar
  45. 45.
    Goldman JG, Weis H, Stebbins G, Bernard B, Goetz CG (2012) Clinical differences among mild cognitive impairment subtypes in Parkinson’s disease. Mov Disord 27:1129–1136PubMedCentralCrossRefPubMedGoogle Scholar
  46. 46.
    Marras C, Armstrong MJ, Meaney CA et al (2013) Measuring mild cognitive impairment in patients with Parkinson’s disease. Mov Disord 28:626–633PubMedCentralCrossRefPubMedGoogle Scholar
  47. 47.
    Ray NJ, Strafella AP (2012) The neurobiology and neural circuitry of cognitive changes in Parkinson’s disease revealed by functional neuroimaging. Mov Disord 27:1484–1492PubMedCentralCrossRefPubMedGoogle Scholar
  48. 48.
    Kehagia AA, Barker RA, Robbins TW (2010) Neuropsychological and clinical heterogeneity of cognitive impairment and dementia in patients with Parkinson’s disease. Lancet Neurol 9:1200–1213CrossRefPubMedGoogle Scholar
  49. 49.
    Lee JE, Cho KH, Song SK et al (2014) Exploratory analysis of neuropsychological and neuroanatomical correlates of progressive mild cognitive impairment in Parkinson’s disease. J Neurol Neurosurg Psychiatry 85(1):7–16CrossRefPubMedGoogle Scholar
  50. 50.
    Ekman U, Eriksson J, Forsgren L, Mo SJ, Riklund K, Nyberg L (2012) Functional brain activity and presynaptic dopamine uptake in patients with Parkinson’s disease and mild cognitive impairment: a cross-sectional study. Lancet Neurol 11:679–687CrossRefPubMedGoogle Scholar
  51. 51.
    Nagano-Saito A, Habak C, Mejìa-Constaìn B et al (2014) Effect of mild cognitive impairment on the patterns of neural activity in early Parkinson’s disease. Neurobiol Aging 35:223–231CrossRefPubMedGoogle Scholar
  52. 52.
    Possin KL, Knag GA, Guo C et al (2013) Rivastigmine is associated with restoration of left frontal brain activity in Parkinson’s disease. Mov Disord 28:1384–1390PubMedCentralCrossRefPubMedGoogle Scholar
  53. 53.
    Crucian GP, Barrett AM, Schwartz RL et al (2000) Cognitive and vestibulo-proprioceptive components of spatial ability in Parkinson’s disease. Neuropsychologia 38(6):757–767CrossRefPubMedGoogle Scholar
  54. 54.
    Chow TW, Cummings J (2007) Frontal-subcortical circuits. In: Miller BL, Cummings J (eds) The human frontal lobes: functions and disorders: (science and practice of neuropsychology series). The Guilford Press, New YorkGoogle Scholar
  55. 55.
    Cohn M, Moscovitch M, Davidson PS (2010) Double dissociation between familiarity and recollection in Parkinson’s disease as a function of encoding tasks. Neuropsychologia 48:4142–4147CrossRefPubMedGoogle Scholar
  56. 56.
    Hanganu A, Bedetti C, Jubault T et al (2013) Mild cognitive impairment in patients with Parkinson’s disease is associated with increased cortical degeneration. Mov Disord 28:1360–1369CrossRefPubMedGoogle Scholar
  57. 57.
    Segura B, Baggio HC, Marti MJ, et al (2014) Cortical thinning associated with mild cognitive impairment in Parkinson’s disease. Mov Disord 2014 Aug 7. (Epub ahead of print)Google Scholar
  58. 58.
    Pereira JB, Ibarretxe-Bilbao N, Marti MJ, Compta Y (2012) Assessment of cortical degeneration in patients with Parkinson’s disease by voxel-based morphometry, cortical folding, and cortical thickness. Hum Brain Mapp 33(11):2521–2534CrossRefPubMedGoogle Scholar
  59. 59.
    Tang-Wai DF, Knopman DS, Geda YE et al (2003) Comparison of the short test of mental status and the mini-mental state examination in mild cognitive impairment. Arch Neurol 60(12):1777–1781CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Marianna Amboni
    • 1
    • 2
  • Alessandro Tessitore
    • 3
  • Fabrizio Esposito
    • 1
    • 4
  • Gabriella Santangelo
    • 5
  • Marina Picillo
    • 1
  • Carmine Vitale
    • 2
    • 6
  • Alfonso Giordano
    • 2
    • 3
  • Roberto Erro
    • 1
  • Rosa de Micco
    • 3
  • Daniele Corbo
    • 3
  • Gioacchino Tedeschi
    • 3
  • Paolo Barone
    • 1
    • 2
  1. 1.Neurodegenerative Diseases Center, Department of Medicine and SurgeryUniversity of SalernoBaronissiItaly
  2. 2.Istituto di Diagnosi e Cura Hermitage-CapodimonteNaplesItaly
  3. 3.Department of NeurologySecond University of NaplesNaplesItaly
  4. 4.Department of Cognitive NeuroscienceMaastricht UniversityMaastrichtThe Netherlands
  5. 5.Neuropsychology Laboratory, Department of PsychologySecond University of NaplesCasertaItaly
  6. 6.University ParthenopeNaplesItaly

Personalised recommendations