Swallowing and chewing difficulties are associated with presynaptic dopaminergic dysfunction and greater non-motor symptom burden in early drug-naïve Parkinson’s patients

Abstract

Background The underlying pathophysiology of swallowing and chewing difficulties is multifactorial and evidence clarifying the precise mechanisms are scarce. Dysfunction in dopamine-related and non-dopamine-related pathways, changes in cortical networks related with swallowing and peripheral mechanisms have been implicated in the pathogenesis of swallowing difficulties. We aimed at investigating whether swallowing and chewing difficulties are associated with presynaptic dopaminergic deficits, faster motor symptom progression and cognitive decline in a population of early drug-naïve patients with Parkinson’s disease. Methods By exploring the database of Parkinson’s Progression Markers Initiative we identified forty-nine early drug-naïve Parkinson’s disease patients with swallowing difficulties. Swallowing and chewing impairment was identified with SCOPA-AUT question 1 (answer regularly) and was assessed with MDS-UPDRS Part-II, Item 2.3 (Chewing and Swallowing). We compared Parkinson’s disease patients with swallowing and chewing difficulties to Parkinson’s disease patients without difficulties, and investigated differences in striatal [123I]FP-CIT single photon emission computed tomography levels. Using Cox proportional hazards analyses, we also evaluated whether swallowing impairment can predict motor deterioration and cognitive dysfunction. Results Patients with Parkinson’s disease, harbored a greater deterioration regarding motor and non-motor symptoms and decreased [123I]FP-CIT binding when compared with patients without swallowing and chewing impairment. Higher burden of swallowing and chewing dysfunction (MDS-UPDRS-II, item 2.3) was correlated with lower [123I]FP-CIT uptakes within the striatum (rs=−0.157; P=0.002) and the caudate (rs=−0.156; P=0.002). The presence of swallowing and chewing difficulties was not a predictor of motor progression (Hazard ratio [HR]: 1.143, 95% confidence interval [CI]: 0.848–1.541; P=0.379) or cognitive decline (HR: 1.294, 95% CI: 0.616–2.719; P=0.496). Conclusions Swallowing and chewing impairment is associated with decreased presynaptic dopaminergic integrity within caudate and greater motor and non-motor symptoms burden in early drug-naïve PD. Author contributions S.P. and M.P. conceived the study, conceptualized the experimental design. M.P., S.P., G.D. and G.P. gave input to experimental design. S.P. wrote the first draft and prepared the manuscript. G.P. and S.P. performed the statistical analysis. G.P., G.D., T.Y. and S.P. generated the figures. F.N., M.P., S.P., G.P., G.D. interpreted the data. All authors revised and gave input to the manuscript. Financial Disclosure Statement Data used in the preparation of this article were obtained from the Parkinson’s Progression Markers Initiative (PPMI) database (www.ppmi-info.org/data). For up-to-date information on the study, visit www.ppmi-info.org. PPMI – a public-private partnership - is sponsored by the Michael J. Fox Foundation for Parkinson’s Research (MJFF) and is co-funded by MJFF, Abbvie, Avid Radiopharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Covance, Eli Lilly & Co., F. Hoffman-La Roche, Ltd., GE Healthcare, Genentech, GlaxoSmithKline, Lundbeck, Merck, MesoScale, Piramal, Pfizer and UCB.PPMI. Industry partners are contributing to PPMI through financial and in-kind donations and are playing a lead role in providing feedback on study parameters through the Industry Scientific Advisory Board (ISAB). Through close interaction with the study, the ISAB is positioned to inform the selection and review of potential progression markers that could be used in clinical testing. Mr. Polychronis, Dr. Dervenoulas, Ms Yousaf, Dr. Niccolini, Dr. Pagano and Prof. Politis report no disclosures. Potential Conflicts of Interest No potential conflict of interest relevant to this article was reported.