Extrastriatal dopaminergic and serotonergic pathways in Parkinson’s disease and in dementia with Lewy bodies: a 123I-FP-CIT SPECT study

  • Andrea PilottoEmail author
  • Francesca Schiano di Cola
  • Enrico Premi
  • Roberto Grasso
  • Rosanna Turrone
  • Stefano Gipponi
  • Andrea Scalvini
  • Elisabetta Cottini
  • Barbara Paghera
  • Valentina Garibotto
  • Maria Cristina Rizzetti
  • Laura Bonanni
  • Barbara Borroni
  • Silvia Morbelli
  • Flavio Nobili
  • Ugo Paolo Guerra
  • Daniela Perani
  • Alessandro Padovani
Original Article



The aim of the study was to evaluate extrastriatal dopaminergic and serotonergic pathways in patients with Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) using 123I-FP-CIT SPECT imaging.


The study groups comprised 56 PD patients without dementia, 41 DLB patients and 54 controls. Each patient underwent a standardized neurological examination and 123I-FP-CIT SPECT. Binding in nigrostriatal and extrastriatal regions of interest was calculated in each patient from spatially normalized images. The occipital-adjusted specific to nondisplaceable binding ratio (SBR) in the different regions was compared among the PD patients, DLB patients and controls adjusting for the effects of age, sex, disease duration and serotonergic/dopaminergic treatment. Covariance analysis was used to determine the correlates of local and long-distance regions with extrastriatal 123I-FP-CIT deficits.


Both PD and DLB patients showed lower 123I-FP-CIT SPECT SBR in several regions beyond the nigrostriatal system, especially the insula, cingulate and thalamus. DLB patients showed significantly lower 123I-FP-CIT SBR in the thalamus than controls and PD patients. Thalamic and cingulate 123I-FP-CIT SBR deficits were correlated, respectively, with limbic serotonergic and widespread cortical monoaminergic projections only in DLB patients but exhibited only local correlations in PD patients and controls.


PD and DLB patients both showed insular dopamine deficits, whereas impairment of thalamic serotonergic pathways was specifically associated with DLB. Longitudinal studies are necessary to determine the clinical value of the assessment of extrastriatal 123I-FP-CIT SPECT.


Parkinson’s disease Dementia with Lewy bodies 123I-FP-CIT SPECT Serotonin Dopamine 


Authors’ roles

Andrea Pilotto: study concept and design, acquisition of data, statistical analysis design and execution, interpretation of data, drafting/revising the manuscript for content.

Francesca Schiano di Cola: acquisition of data, statistical analysis execution, interpretation of data, drafting/revising the manuscript for content.

Enrico Premi: statistical analysis design and interpretation of data, revising the manuscript for content.

Roberto Grasso: acquisition of data, revising the manuscript for content.

Rosanna Turrone: acquisition of data, revising the manuscript for content.

Stefano Gipponi: acquisition of data, revising the manuscript for content.

Andrea Scalvini acquisition of data, revising the manuscript for content.

Elisabetta Cottini: acquisition of data, revising the manuscript for content.

Barbara Paghera: acquisition of data, revising the manuscript for content.

Valentina Garibotto: revising the manuscript for content.

Maria Cristina Rizzetti: revising the manuscript for content.

Laura Bonanni: revising the manuscript for content.

Barbara Borroni: revising the manuscript for content.

Silvia Morbelli: revising the manuscript for content.

Flavio Nobili: revising the manuscript for content.

Ugo Paolo Guerra: revising the manuscript for content.

Daniela Perani: revising the manuscript for content.

Alessandro Padovani: study concept and design, acquisition of data, analysis and interpretation of data, drafting/revising the manuscript for content.

Compliance with ethical standards

Conflicts of interest

Andrea Pilotto received speaker honoraria from BioMarin Pharmaceutical, Chiesi Pharmaceuticals, Nutricia Pharmaceuticals, UCB Pharma and Zambon Pharmaceuticals. He received travel grants from AbbVie Pharmaceuticals, BioMarin Pharmaceutical, Nutricia Pharmaceuticals, Zambon Pharmaceuticals and the Italian Movement Disorder Society.

Valentina Garibotto is funded by a grant from the Swiss National Science Foundation (SNF 320030_169876) and from the Velux Foundation (project 1123).

Silvia Morbelli acted as consultant for Eli Lilly in 2014 and for Avid Radiopharmaceuticals in 2016. She received speaker honoraria from General Electric Healthcare in 2017.

Daniela Perani is funded by a grant from Fondazione Cariplo, Bando Ricerca 2014 Malattie Invecchiamento, project title “Evaluation of autonomic, genetic, imaging and biochemical markers for Parkinson-related dementia,” 2015–2017, and the EU FP7 INMIND project (FP7-HEALTH-2013, grant agreement 278,850).

Alessandro Padovani is a consultant for and served on the scientific advisory board of GE Healthcare, Eli Lilly, and Actelion Ltd. Pharmaceuticals, received speaker honoraria from Nutricia, PIAM, Langstone Technology, GE Healthcare, Lilly, UCB Pharma, Zambon and Chiesi Pharmaceuticals. He is funded by a grant from the Ministry of University and Research (MURST).

All other authors declare no conflicts of interest.

Ethical approval

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 principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Andrea Pilotto
    • 1
    • 2
    Email author
  • Francesca Schiano di Cola
    • 1
  • Enrico Premi
    • 1
    • 3
  • Roberto Grasso
    • 1
  • Rosanna Turrone
    • 1
  • Stefano Gipponi
    • 1
  • Andrea Scalvini
    • 1
  • Elisabetta Cottini
    • 1
  • Barbara Paghera
    • 4
  • Valentina Garibotto
    • 5
  • Maria Cristina Rizzetti
    • 2
  • Laura Bonanni
    • 6
  • Barbara Borroni
    • 1
  • Silvia Morbelli
    • 7
    • 8
  • Flavio Nobili
    • 8
    • 9
  • Ugo Paolo Guerra
    • 10
  • Daniela Perani
    • 11
  • Alessandro Padovani
    • 1
  1. 1.Neurology Unit, Department of Clinical and Experimental SciencesUniversity of BresciaBresciaItaly
  2. 2.Parkinson’s Disease Rehabilitation Centre, FERB ONLUS – S. Isidoro HospitalTrescore BalnearioItaly
  3. 3.Stroke Unit, Azienda Socio Sanitaria Territoriale Spedali CiviliSpedali Civili HospitalBresciaItaly
  4. 4.Nuclear Medicine UnitUniversity of BresciaBresciaItaly
  5. 5.Department of Medical ImagingGeneva University HospitalGenevaSwitzerland
  6. 6.Department of Neuroscience Imaging and Clinical SciencesUniversity G. d’Annunzio of Chieti-PescaraChietiItaly
  7. 7.Nuclear Medicine Unit, Department of Health SciencesUniversity of GenoaGenoaItaly
  8. 8.IRCCS ospedale Policlinico San MartinoGenoaItaly
  9. 9.Department of Neuroscience (DINOGMI)University of GenoaGenoaItaly
  10. 10.Nuclear Medicine UnitPoliambulanza HospitalBresciaItaly
  11. 11.Nuclear Medicine Unit San Raffaele HospitalDivision of Neuroscience San Raffaele Scientific InstituteMilanItaly

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