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Clinical implications of early caudate dysfunction in Parkinson’s disease

Lookup NU author(s): Dr Rory Durcan, Dr Lou Wiblin, Professor Lynn Rochester, Professor David Brooks, Professor David Burn, Professor Nicola Pavese

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by BMJ, 2019.

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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 SPECT and determined whether it was associated with the presence or subsequent development of cognitive impairment, depression, sleep and gait problems. MethodsPD patients and healthy controls were identified from the Parkinson’s Progression Markers Initiative database. We defined a clinically significant caudate dysfunction as 123I-FP-CIT binding <-2 standard deviations compared to 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 DAT binding, 26.0% had unilateral caudate involvement, 22.4% had bilaterally impaired caudate. Compared to those with a baseline normal caudate function, at the four-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 four years (unilateral 22.5%, bilateral 66.5%).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 four years.


Publication metadata

Author(s): Pasquini J, Durcan R, Wiblin L, Stokholm MG, Lynn Rochester L, Brooks DJ, Burn D, Pavese N

Publication type: Article

Publication status: Published

Journal: Journal of Neurology, Neurosurgery & Psychiatry

Year: 2019

Pages: Epub ahead of print

Online publication date: 11/05/2019

Acceptance date: 15/04/2019

Date deposited: 29/04/2019

ISSN (print): 0022-3050

ISSN (electronic): 1468-330X

Publisher: BMJ

URL: https://doi.org/10.1136/jnnp-2018-320157

DOI: 10.1136/jnnp-2018-320157


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