Early constipation predicts faster dementia onset in Parkinson’s disease

Marta Camacho* (Corresponding Author), Angus MacLeod, Jodi Maple-Grødem, Jonathan Evans, David Breen, Gemma Cummings, Ruwani Wijeyekoon, Julia Greenland, Guido Alves, Ole-Bjørn Tysnes, Rachel Lawson, Roger A Barker, Caroline Williams-Gray

*Corresponding author for this work

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Constipation is a common but not a universal feature in early PD, suggesting that gut involvement is heterogeneous and may be part of a distinct PD subtype with prognostic implications. We analysed data from the Parkinson’s Incidence Cohorts Collaboration, composed of incident community-based cohorts of PD patients assessed longitudinally over 8 years. Constipation was assessed with the MDS-UPDRS constipation item or a comparable categorical scale. Primary PD outcomes of interest were dementia, postural instability and death. PD patients were stratified according to constipation severity at diagnosis: none (n = 313, 67.3%), minor (n = 97, 20.9%) and major (n = 55, 11.8%). Clinical progression to all three outcomes was more rapid in those with more severe constipation at baseline (Kaplan–Meier survival analysis). Cox regression analysis, adjusting for relevant confounders, confirmed a significant relationship between constipation severity and progression to dementia, but not postural instability or death. Early constipation may predict an accelerated progression of neurodegenerative pathology.
Original languageEnglish
Article number45
Number of pages7
Journalnpj Parkinson's Disease
Early online date26 May 2021
Publication statusPublished - 2021

Bibliographical note

We would like to thank all participants and funders of PICC and of the individual cohort studies. Members of PICC Steering Group: Dr. Angus D. Macleod, Dr. Carl E. Counsell, University of Aberdeen (chairperson), UK; Prof. Ole-Bjørn Tysnes, University of Bergen, Norway; Marta Camacho, Dr. Caroline Williams-Gray, University of Cambridge, UK; Dr. Rachael A. Lawson, Newcastle University, UK; Dr. Jodi Maple-Grødem, Prof. Guido Alves, Stavanger University Hospital, Norway; Prof. Lars Forgren, Umeå, Dr. David Backstrom, University, Sweden. We acknowledge the contributions of members of the individual study groups: PICNICS study: Principal investigators: Roger A. Barker, Caroline H. Williams-Gray. Study personnel: Jonathan Evans, Gemma Cummins, David P. Breen, Ruwani Wijeyekoon, Kirsten Scott, Tom Stoker, Julia Greenland, Marta Camacho, Natalie Valle Guzman, Lucy Collins, Simon Stott and Sarah Mason. ParkWest Study: ParkWest Principal investigators: Guido Alves (Norwegian Centre for Movement Disorders, Stavanger University Hospital) and Ole-Bjørn Tysnes (Haukeland University Hospital). Study personnel: Michaela Dreetz Gjerstad, Kenn Freddy Pedersen, Elin Bjelland Forsaa, Veslemøy Hamre Frantzen, Anita Laugaland, Jodi Maple-Grødem, Johannes Lange, Karen Simonsen, Eldbjørg Fiske and Ingvild Dalen, Bernd Müller, Geir Olve Skeie and Marit Renså; Wenche Telstad, Aliaksei Labusau and Jane Kastet; Ineke HogenEsch, Marianne Kjerandsen and Liv Kari Håland; Karen Herlofson, Solgunn Ongre and Siri Bruun. The PICC collaboration was funded by the Chief Scientist Office of the Scottish Government, NHS Education for Scotland, and the Academy of Medical Sciences. The PICNICS study has received funding from the Cure Parkinson’s Trust, the Van Geest Foundation, the Medical Research Council (MRC) and Parkinson’s UK. This work was also supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre Dementia and Neurodegeneration Theme (grant no. 146281). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. M.C. is supported by Centre for Parkinson’s Plus and funded by the Evelyn Trust (proj ref 19/24). R.A.B. is supported by the Wellcome Trust Stem Cell Institute (Cambridge 203151/Z/16/Z). D.P.B. is supported by a Wellcome Clinical Research Career Development Fellowship (214571/Z/18/Z). C.H.W.G. is supported by a RCUK/UKRI Research Innovation Fellowship awarded by the MRC (MR/R007446/1) and by the Cambridge Centre for Parkinson-Plus. The Norwegian ParkWest study has been funded by the Research Council of Norway (grant number 177966) and the Western Norway Regional Health Authority (grant number 911218), and the Norwegian Parkinson’s Disease Association. J.M.-G. and G.A. are supported by the Research Council of Norway (grant number 287842). R.A.L. is supported by a Senior Research Fellowship from Parkinson’s UK (F-1801).

Data Availability Statement

Data availability
Anonymized data for all six cohorts included in PICC are available upon reasonable request by any qualified investigator.

Code availability
No custom codes were used. All software and packages, their versions, relevant specification and parameters are stated in the ‘Methods' section.


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