Clinical implications of early caudate dysfunction in Parkinson's disease

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DOI

  • Jacopo Pasquini, University of Milan - Department of Neurology-Stroke Unit and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy.
  • ,
  • Rory Durcan, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
  • ,
  • Louise Wiblin, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
  • ,
  • Morten Gersel Stokholm
  • Lynn Rochester, Newcastle upon Tyne Hospitals NHS Foundation Trust
  • ,
  • David James Brooks
  • David Burn, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
  • ,
  • Nicola Pavese

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.

Original languageEnglish
JournalJournal of neurology, neurosurgery, and psychiatry
Volume90
Issue10
Pages (from-to)1098-1104
Number of pages7
ISSN0022-3050
DOIs
Publication statusPublished - 2019

    Research areas

  • MILD COGNITIVE IMPAIRMENT, STRIATAL DOPAMINE TRANSPORTERS, DIAGNOSTIC-CRITERIA, SPECT, PROGRESSION, SYMPTOMS, DISORDER, SYSTEM, DENERVATION, MARKER, caudate, cognitive impairment, gait problems, depression, parkinson's disease

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