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Constipation is not associated with dopamine transporter pathology in early drug-naïve patients with Parkinson's disease

Research output: Contribution to journalArticle

Original languageEnglish
JournalEuropean Journal of Neurology
Early online date11 Dec 2017
DOIs
StateE-pub ahead of print - 11 Dec 2017

King's Authors

Abstract

Background and purpose: Constipation is a common non-motor symptom of Parkinson's disease (PD). Deposition of α-synuclein inclusions that spread from the gut to the substantia nigra through the vagus nerve has recently been speculated to be a pre-motor and early stage of PD. The aim of the study was to investigate whether constipation is associated with dopaminergic pathology on dopamine transporter (DAT) single-photon emission computed tomography in early drug-naïve patients with PD. Our hypothesis was that constipation is associated with other signs of pre-motor PD and is independent of DAT pathology. We then investigated for associations with motor and non-motor symptoms, and with cerebrospinal fluid biomarkers of PD pathology. Methods: Using the Parkinson's Progression Markers Initiative database, we investigated the prevalence of constipation and the association between constipation and clinical features, striatal [123I]Ioflupane uptake and non-imaging (cerebrospinal fluid and serum) biomarkers. Constipation was evaluated using Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I item 1.11. Results: One third (132/398) of de-novo patients with PD had constipation. Higher severity of constipation correlated with older age (r = 0.728, P < 0.001), higher MDS-UPDRS total score (r = 0.285, P < 0.001), worse postural instability (r = 0.190, P = 0.012), rapid eye movement sleep behaviour disorder (r = 0.228, P < 0.0001) and depression (r = 0.187, P = 0.024). No correlation was found with cerebrospinal fluid, serum and imaging markers of PD pathology. Conclusions: Constipation was not associated with DAT pathology but with rapid eye movement sleep behaviour disorder and depression, which are speculated to be pre-motor symptoms of PD. This confirms the hypothesis that constipation may be a pre-motor sign of PD due to an impairment of non-dopaminergic pathways.

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