{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T05:42:08Z","timestamp":1784266928106,"version":"3.55.0"},"reference-count":37,"publisher":"SAGE Publications","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPD"],"published-print":{"date-parts":[[2021,8,2]]},"abstract":"<jats:p>Background: Constipation is regarded as one of the prodromal features of Parkinson\u2019s disease (PD) and there is emerging evidence linking gastrointestinal dysfunction and cognitive impairment (CI) in PD. Objective: We explored whether constipation is associated with development of CI in two independent cohorts of de novo PD patients (n\u200a=\u200a196 from the Non-motor International Longitudinal Study [NILS] and n\u200a=\u200a423 from the Parkinson\u2019s Progression Markers Initiative [PPMI] study). Methods: Constipation was clinically defined using the Non-Motor Symptoms Scale (NMSS) item-21 [NILS] and Scales for Outcomes in PD-Autonomic (SCOPA-AUT) item-5 [PPMI]. We assessed baseline group differences (PD with or without constipation) in CI, global non-motor symptoms burden, motor dysfunction, and striatal dopaminergic denervation. Kaplan-Meier method estimated group differences in cumulative proportion of patients with incident CI over three years. In PPMI, we subsequently performed univariate and multivariate Cox survival analyses to evaluate whether constipation predicts incident mild cognitive impairment or dementia over a 6-year period, including constipation and other known predictors of CI as covariates. Results: Patients with constipation had greater motor and global non-motor burden in both cohorts at baseline (p\u200a&lt;\u200a0.05). Kaplan-Meier plots showed faster conversion to CI in patients with constipation in both cohorts (p\u200a&lt;\u200a0.05). In PPMI, 37 subjects developed dementia during a mean follow-up of 4.9 years, and constipation was an independent predictor of dementia onset (hazard ratio\u200a=\u200a2.311; p\u200a=\u200a0.02). Conclusion: Constipation in de novo PD patients is associated with development of cognitive decline and may serve as a clinical biomarker for identification of patients at risk for cognitive impairment.<\/jats:p>","DOI":"10.3233\/jpd-212570","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T13:05:09Z","timestamp":1617714309000},"page":"1209-1219","source":"Crossref","is-referenced-by-count":53,"title":["Constipation is Associated with Development of Cognitive Impairment in de novo Parkinson\u2019s Disease: A Longitudinal Analysis of Two International Cohorts"],"prefix":"10.1177","volume":"11","author":[{"given":"Valentina","family":"Leta","sequence":"first","affiliation":[{"name":"Institute of Psychiatry, Psychology & Neuroscience, Department of Neurosciences, King\u2019s College London, London, United Kingdom"},{"name":"Parkinson\u2019s Foundation Centre of Excellence, King\u2019s College Hospital, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Urso","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry, Psychology & Neuroscience, Department of Neurosciences, King\u2019s College London, London, United Kingdom"},{"name":"Parkinson\u2019s Foundation Centre of Excellence, King\u2019s College Hospital, London, United Kingdom"},{"name":"Center for Neurodegenerative Diseases and the Aging Brain, Department of Clinical Research in Neurology, University of Bari \u2018Aldo Moro\u2019, Tricase, Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Batzu","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry, Psychology & Neuroscience, Department of Neurosciences, King\u2019s College London, London, United Kingdom"},{"name":"Parkinson\u2019s Foundation Centre of Excellence, King\u2019s College Hospital, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Weintraub","sequence":"additional","affiliation":[{"name":"University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataliya","family":"Titova","sequence":"additional","affiliation":[{"name":"Federal State Autonomous Educational Institution of Higher Education \u201cN.I. Pirogov Russian National Research Medical University\u201d of the Ministry of Health of the Russian Federation, Department of Neurology, Neurosurgery and Medical Genetics, Moscow, Russia"},{"name":"Federal State Budgetary Institution \u201cFederal Center of Brain and Neurotechnologies\u201d of the Ministry of Health of the Russian Federation, Department of Neurodegenerative Diseases, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dag","family":"Aarsland","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry, Psychology & Neuroscience, Department of Neurosciences, King\u2019s College London, London, United Kingdom"},{"name":"Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Martinez-Martin","sequence":"additional","affiliation":[{"name":"Centre for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), Carlos III Institute of Health, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Borghammer","sequence":"additional","affiliation":[{"name":"Institute for Clinical Medicine, Aarhus University, Aarhus, Denmark"},{"name":"Nuclear Medicine and PET, Aarhus University Hospital, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"van Wamelen","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry, Psychology & Neuroscience, Department of Neurosciences, King\u2019s College London, London, United Kingdom"},{"name":"Parkinson\u2019s Foundation Centre of Excellence, King\u2019s College Hospital, London, United Kingdom"},{"name":"Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tayyabah","family":"Yousaf","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry, Psychology & Neuroscience, Department of Neurosciences, King\u2019s College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Rizos","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry, Psychology & Neuroscience, Department of Neurosciences, King\u2019s College London, London, United Kingdom"},{"name":"Parkinson\u2019s Foundation Centre of Excellence, King\u2019s College Hospital, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Rodriguez-Blazquez","sequence":"additional","affiliation":[{"name":"National Centre of Epidemiology, Carlos III Institute of Health, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Chung-Faye","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, King\u2019s College Hospital Foundation NHS Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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