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Research paper
Clinical implications of early caudate dysfunction in Parkinson’s disease
  1. Jacopo Pasquini1,2,
  2. Rory Durcan3,
  3. Louise Wiblin3,
  4. Morten Gersel Stokholm4,
  5. Lynn Rochester3,5,
  6. David James Brooks3,4,
  7. David Burn5,6,
  8. Nicola Pavese3,4
  1. 1Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, University of Milan, Milan, Italy
  2. 2Department of Neurology - Stroke Unit and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy
  3. 3Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
  4. 4Department of Nuclear Medicine and PET Centre, Aarhus Universitetshospital, Aarhus, Denmark
  5. 5Newcastle upon Tyne Hospitals, NHS Foundation Trust, Newcastle upon Tyne, UK
  6. 6Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
  1. Correspondence to Professor Nicola Pavese, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE1 7RU, Tyne and Wear, UK; Nicola.Pavese{at}newcastle.ac.uk

Abstract

Objective Although not typical of Parkinson’s disease (PD), caudate dopaminergic dysfunction can occur in early stages of the disease. However, its frequency and longitudinal implications in large cohorts of recently diagnosed patients remain to be established. We investigated the occurrence of caudate dopaminergic dysfunction in the very early phases of PD (<2 years from diagnosis) using 123I-FP-CIT single photon emission CT and determined whether it was associated with the presence or subsequent development of cognitive impairment, depression, sleep and gait problems.

Methods Patients with PD and healthy controls were identified from the Parkinson’s Progression Markers Initiative (PPMI) database. We defined a clinically significant caudate dysfunction as 123I-FP-CIT binding <–2 SDs compared with the controls’ mean and categorised three groups accordingly (no reduction, unilateral reduction, bilateral reduction). All statistical analyses were adjusted for mean putamen binding.

Results At baseline, 51.6% of 397 patients had normal caudate dopamine transporter binding, 26.0% had unilateral caudate involvement, 22.4% had bilaterally impaired caudate.

Compared with those with a baseline normal caudate function, at the4-year follow-up patients with a baseline bilateral caudate involvement showed a higher frequency of cognitive impairment (p<0.001) and depression (p<0.001), and worse cognitive (p<0.001), depression (<0.05) and gait (<0.001) ratings. Significant caudate involvement was observed in 83.9% of the population after 4 years (unilateral 22.5%, bilateral 61.4%).

Conclusions Early significant caudate dopaminergic denervation was found in half of the cases in the PPMI series. Baseline bilateral caudate involvement was associated with increased risk of developing cognitive impairment, depression and gait problems over the next 4 years.

  • parkinson’s disease
  • caudate
  • cognitive impairment
  • depression
  • gait problems

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Footnotes

  • JP and RD contributed equally.

  • Contributors Study conception and design: JP, RD, NP. Data analysis organisation and execution: JP, RD, NP. Writing of the manuscript: JP, RD, LW, MGS, LR, DJB, DB, NP. Critical revision of the manuscript: LR, DJB, DB, NP.

  • Funding No funding was provided for the analysis reported in this study. The Parkinson’s Progression Markers Initiative—a public- private partnership—is funded by the Michael J. Fox Foundation for Parkinson’s Research and funding partners including AbbVie, Allergan, Avid, Biogen, BioLegend, Bristol-Myers Squibb, Celgene, Denali Therapeutics, GE Healthcare, Genentech, GlaxoSmithKline, Lilly, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Prevail Therapeutics, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Verily, Voyager Therapeutics and Golub Capital.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval All participating PPMI sites received approval from an ethical standards committee prior to study initiation and written informed consent for research was obtained from all participants in the study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request.

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