{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T13:19:46Z","timestamp":1786713586150,"version":"build-2736575974"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Shenzhen Science and Technology Program","award":["KQTD20190929172835662"],"award-info":[{"award-number":["KQTD20190929172835662"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82,404,371"],"award-info":[{"award-number":["82,404,371"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Previous research indicates that constipation may be an early symptom of Parkinson\u2019s disease (PD). However, it remains uncertain whether constipation is a unique symptom prior to PD or to other major neurological disorders as well. This study aimed to explore the association between premorbid constipation and three major neurological disorders: stroke, dementia and PD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a retrospective cohort study using data from UK Biobank. Constipation was defined based on diagnosed cases in electronic health records, self-reported instances or regular laxative use. The primary outcome was defined as the first onset of any of three neurological disorders: stroke, dementia and PD. Cox regression was used to adjust for socio-demographic characteristics, lifestyle factors, medical conditions and regular medication use.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Out of 462,327 eligible participants, those with constipation were associated with higher incidence of three outcome diseases (1415\/20,263 [7.0%]) than those without (18,848\/442,064 [4.3%]), with adjusted hazard ratio (HR) being 1.35 [1.27\u20131.42]. Specifically, those with constipation had a 20%, 50% and 56% higher risk of stroke, dementia and PD, respectively. Both self-reported and diagnosed constipation were associated with a higher risk of these conditions, with HR being 1.31 (1.23\u20131.40) and 1.44 (1.30\u20131.59), respectively. Interestingly, the association between constipation and neurological disorders was stronger within the first 2 years from baseline.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>These findings support the biological link between constipation and neurological disorders. Given its potential role as a prodromal symptom for these diseases, both diagnosed and self-reported constipation should be considered in risk prediction models.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ageing\/afaf257","type":"journal-article","created":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T13:48:08Z","timestamp":1758462488000},"source":"Crossref","is-referenced-by-count":4,"title":["Constipation preceding stroke, dementia and Parkinson\u2019s disease in middle-aged and older adults: a population-based cohort study"],"prefix":"10.1093","volume":"54","author":[{"given":"Qingping","family":"Yun","sequence":"first","affiliation":[{"name":"School of Public Health, Hainan Medical University , Haikou ,","place":["China"]},{"name":"Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Yong Loo Lin School of Medicine, National University of Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8516-958X","authenticated-orcid":false,"given":"Bingyu","family":"Li","sequence":"additional","affiliation":[{"name":"School of Government, Sociology, Shenzhen University , 803 Minglv Building, Lihu Campus, Shenzhen, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirong","family":"Yang","sequence":"additional","affiliation":[{"name":"Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen, Guangdong ,","place":["China"]},{"name":"Cambridge University , Cambridge, Cambridgeshire ,","place":["UK"]},{"name":"Department of Computational Biology and Medical Big Data, Shenzhen University of Advanced Technology , Shenzhen, Guangdong ,","place":["China"]},{"name":"Center for AI in Medicine, Artificial Intelligence Research Institute, Shenzhen University of Advanced Technology , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Erasmus University Rotterdam , Rotterdam, ZH ,","place":["Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinqiu","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics , Clinical Research Center, , Shenzhen, Guangdong ,","place":["China"]},{"name":"The Seventh Affiliated Hospital Sun Yat-sen University , Clinical Research Center, , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University Shenzhen Hospital , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Li","sequence":"additional","affiliation":[{"name":"Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2386-2431","authenticated-orcid":false,"given":"Zuyao","family":"Yang","sequence":"additional","affiliation":[{"name":"The JC School of Public Health & Primary Care, The Chinese University of Hong Kong ,","place":["Hong Kong"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Sha","sequence":"additional","affiliation":[{"name":"Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinling","family":"Tang","sequence":"additional","affiliation":[{"name":"Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen, Guangdong ,","place":["China"]},{"name":"Department of Computational Biology and Medical Big Data, Shenzhen University of Advanced Technology , Shenzhen, Guangdong ,","place":["China"]},{"name":"Center for AI in Medicine, Artificial Intelligence Research Institute, Shenzhen University of Advanced Technology , Shenzhen, Guangdong ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,21]]},"reference":[{"key":"2025092109480316500_ref1","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/s1474-4422(24)00038-3","article-title":"Global, regional, and national burden of disorders affecting the nervous system, 1990-2021: A systematic analysis for the global burden of disease study 2021","volume":"23","author":"GBD 2021 Nervous System Disorders Collaborators","year":"2024","journal-title":"Lancet Neurol"},{"key":"2025092109480316500_ref2","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1016\/s1474-4422(17)30299-5","article-title":"Global, regional, and national burden of neurological disorders during 1990-2015: A systematic analysis for the global burden of disease study 2015","volume":"16","author":"GBD 2015 Neurological Disorders Collaborator Group","year":"2017","journal-title":"Lancet Neurol"},{"key":"2025092109480316500_ref3","doi-asserted-by":"publisher","first-page":"105840","DOI":"10.1016\/j.phrs.2021.105840","article-title":"The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders","volume":"172","author":"Soca\u0142a","year":"2021","journal-title":"Pharmacol Res"},{"key":"2025092109480316500_ref4","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1007\/s00508-023-02156-w","article-title":"Global prevalence of constipation in older adults: A systematic review and meta-analysis","volume":"135","author":"Salari","year":"2023","journal-title":"Wien Klin Wochenschr"},{"key":"2025092109480316500_ref5","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1136\/jnnp.74.1.13","article-title":"Constipation in neurological diseases","volume":"74","author":"Winge","year":"2003","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2025092109480316500_ref6","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1021\/acschemneuro.9b00607","article-title":"Association of Intestinal Disorders with Parkinson's disease and Alzheimer's disease: A systematic review and meta-analysis","volume":"11","author":"Fu","year":"2020","journal-title":"ACS Chem Nerosci"},{"key":"2025092109480316500_ref7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/2047-9158-4-1","article-title":"Meta-analyses on prevalence of selected Parkinson's nonmotor symptoms before and after diagnosis","volume":"4","author":"Chen","year":"2015","journal-title":"Transl Neurodegener"},{"key":"2025092109480316500_ref8","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.parkreldis.2016.05.016","article-title":"Constipation and risk of Parkinson\u2019s disease: A Danish population-based cohort study","volume":"28","author":"Svensson","year":"2016","journal-title":"Parkinsonism Relat Disord"},{"key":"2025092109480316500_ref9","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1093\/aje\/kwr119","article-title":"A prospective study of bowel movement frequency and risk of Parkinson\u2019s disease","volume":"174","author":"Gao","year":"2011","journal-title":"Am J Epidemiol"},{"key":"2025092109480316500_ref10","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1136\/jnnp-2015-311680","article-title":"Constipation preceding Parkinson's disease: A systematic review and meta-analysis","volume":"87","author":"Adams-Carr","year":"2016","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2025092109480316500_ref11","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1159\/000527513","article-title":"Constipation in Parkinson\u2019s disease: A systematic review and meta-analysis","volume":"86","author":"Yao","year":"2023","journal-title":"Eur Neurol"},{"key":"2025092109480316500_ref12","doi-asserted-by":"publisher","first-page":"e7225","DOI":"10.1097\/md.0000000000007225","article-title":"Incidence of constipation in stroke patients: A systematic review and meta-analysis","volume":"96","author":"Li","year":"2017","journal-title":"Medicine"},{"key":"2025092109480316500_ref13","doi-asserted-by":"publisher","first-page":"821654","DOI":"10.3389\/fnins.2021.821654","article-title":"Prevalence of constipation in elderly and its association with dementia and mild cognitive impairment: A cross-sectional study","volume":"15","author":"Wang","year":"2021","journal-title":"Front Neurosci"},{"key":"2025092109480316500_ref14","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17239006","article-title":"Constipation and its associated factors among patients with dementia","volume":"17","author":"Chen","year":"2020","journal-title":"Int J Environ Res Public Health"},{"key":"2025092109480316500_ref15","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1016\/j.amjmed.2011.03.026","article-title":"Constipation and risk of cardiovascular disease among postmenopausal women","volume":"124","author":"Salmoirago-Blotcher","year":"2011","journal-title":"Am J Med"},{"key":"2025092109480316500_ref16","doi-asserted-by":"publisher","first-page":"e037080","DOI":"10.1136\/bmjopen-2020-037080","article-title":"Constipation and risk of cardiovascular diseases: A Danish population-based matched cohort study","volume":"10","author":"Sundb\u00f8ll","year":"2020","journal-title":"BMJ Open"},{"key":"2025092109480316500_ref17","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.atherosclerosis.2018.12.021","article-title":"Constipation and risk of death and cardiovascular events","volume":"281","author":"Sumida","year":"2019","journal-title":"Atherosclerosis"},{"key":"2025092109480316500_ref18","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1016\/j.parkreldis.2014.09.026","article-title":"Risk of Parkinson's disease following severe constipation: A nationwide population-based cohort study","volume":"20","author":"Lin","year":"2014","journal-title":"Parkinsonism Relat Disord"},{"key":"2025092109480316500_ref19","volume-title":"British National Formulary (BNF) 80: September 2020\u2013March 2021","author":"Joint Formulary Committee","year":"2020"},{"key":"2025092109480316500_ref20","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1016\/j.biopsych.2020.11.019","article-title":"Socioeconomic deprivation index is associated with psychiatric disorders: An observational and genome-wide gene-by-environment interaction analysis in the UK biobank cohort","volume":"89","author":"Ye","year":"2021","journal-title":"Biol Psychiatry"},{"key":"2025092109480316500_ref21","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1161\/circulationaha.109.192703","article-title":"Defining and setting national goals for cardiovascular health promotion and disease reduction: The American Heart Association's strategic impact goal through 2020 and beyond","volume":"121","author":"Lloyd-Jones","year":"2010","journal-title":"Circulation"},{"key":"2025092109480316500_ref22","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/s2468-1253(19)30199-2","article-title":"Chronic constipation: New insights, better outcomes?","volume":"4","author":"Schiller","year":"2019","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"2025092109480316500_ref23","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1111\/jgs.13562","article-title":"Prescription opioids and risk of dementia or cognitive decline: A prospective cohort study","volume":"63","author":"Dublin","year":"2015","journal-title":"J Am Geriatr Soc"},{"key":"2025092109480316500_ref24","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.neubiorev.2021.04.031","article-title":"Anticholinergic drugs and the risk of dementia: A systematic review and meta-analysis","volume":"127","author":"Zheng","year":"2021","journal-title":"Neurosci Biobehav Rev"},{"key":"2025092109480316500_ref25","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1016\/S0140-6736(04)16305-8","article-title":"Parkinson's disease","volume":"363","author":"Samii","year":"2004","journal-title":"Lancet"},{"key":"2025092109480316500_ref26","doi-asserted-by":"publisher","first-page":"e646","DOI":"10.1161\/strokeaha.120.033272","article-title":"Drugs associated with ischemic stroke: A review for clinicians","volume":"52","author":"Marto","year":"2021","journal-title":"Stroke"},{"key":"2025092109480316500_ref27","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1080\/03610910902859574","article-title":"Using the standardized difference to compare the prevalence of a binary variable between two groups in observational research","volume":"38","author":"Austin","year":"2009","journal-title":"Commun Stat Simul Comput"},{"key":"2025092109480316500_ref28","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1136\/bmj.330.7497.960","article-title":"Reader's guide to critical appraisal of cohort studies: 2. Assessing potential for confounding","volume":"330","author":"Mamdani","year":"2005","journal-title":"BMJ"},{"key":"2025092109480316500_ref29","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/S1474-4422(14)70287-X","article-title":"Prediagnostic presentations of Parkinson's disease in primary care: A case-control study","volume":"14","author":"Schrag","year":"2015","journal-title":"Lancet Neurol"},{"key":"2025092109480316500_ref30","doi-asserted-by":"publisher","first-page":"e1702","DOI":"10.1212\/wnl.0000000000207081","article-title":"Association between regular laxative use and incident dementia in UK biobank participants","volume":"100","author":"Yang","year":"2023","journal-title":"Neurology"},{"key":"2025092109480316500_ref31","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1002\/mds.23499","article-title":"The patients' perception of prodromal symptoms before the initial diagnosis of Parkinson's disease","volume":"26","author":"Gaenslen","year":"2011","journal-title":"Mov Disord"},{"key":"2025092109480316500_ref32","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.parkreldis.2020.01.009","article-title":"Gastrointestinal symptoms are predictive of trajectories of cognitive functioning in de novo Parkinson's disease","volume":"72","author":"Jones","year":"2020","journal-title":"Parkinsonism Relat Disord"},{"key":"2025092109480316500_ref33","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.3233\/jpd-212570","article-title":"Constipation is associated with development of cognitive impairment in de novo Parkinson's disease: A longitudinal analysis of two international cohorts","volume":"11","author":"Leta","year":"2021","journal-title":"J Parkinsons Dis"},{"key":"2025092109480316500_ref34","doi-asserted-by":"publisher","first-page":"315","DOI":"10.3233\/jpd-212868","article-title":"Constipation predicts cognitive decline in Parkinson's disease: Results from the COPPADIS cohort at 2-year follow-up and comparison with a control group","volume":"12","author":"Santos Garc\u00eda","year":"2022","journal-title":"J Parkinsons Dis"},{"key":"2025092109480316500_ref35","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1176\/appi.ajp.2018.18050566","article-title":"Development and validation of a dementia risk prediction model in the general population: An analysis of three longitudinal studies","volume":"176","author":"Licher","year":"2019","journal-title":"Am J Psychiatry"},{"key":"2025092109480316500_ref36","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/s1474-4422(19)30356-4","article-title":"The gut microbiome in neurological disorders","volume":"19","author":"Cryan","year":"2020","journal-title":"Lancet Neurol"},{"key":"2025092109480316500_ref37","doi-asserted-by":"publisher","first-page":"eabo2984","DOI":"10.1126\/scitranslmed.abo2984","article-title":"Gut microbiome composition may be an indicator of preclinical Alzheimer's disease","volume":"15","author":"Ferreiro","year":"2023","journal-title":"Sci Transl Med"},{"key":"2025092109480316500_ref38","doi-asserted-by":"publisher","first-page":"2068","DOI":"10.1161\/strokeaha.120.030601","article-title":"Autonomic imbalance and risk of dementia and stroke: The Framingham study","volume":"52","author":"Weinstein","year":"2021","journal-title":"Stroke"},{"key":"2025092109480316500_ref39","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1002\/mds.25445","article-title":"Prodromal autonomic symptoms and signs in Parkinson's disease and dementia with Lewy bodies","volume":"28","author":"Postuma","year":"2013","journal-title":"Mov Disord"},{"key":"2025092109480316500_ref40","first-page":"95","article-title":"Autonomic dysfunction","volume":"75","author":"Nakamura","year":"2017","journal-title":"Nihon Rinsho"},{"key":"2025092109480316500_ref41","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1212\/wnl.57.3.456","article-title":"Frequency of bowel movements and the future risk of Parkinson's disease","volume":"57","author":"Abbott","year":"2001","journal-title":"Neurology"},{"key":"2025092109480316500_ref42","doi-asserted-by":"publisher","first-page":"242","DOI":"10.2188\/jea.JE20150123","article-title":"Bowel movement frequency, laxative use, and mortality from coronary heart disease and stroke among Japanese men and women: The Japan collaborative cohort (JACC) study","volume":"26","author":"Kubota","year":"2016","journal-title":"J Epidemiol"},{"key":"2025092109480316500_ref43","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.1111\/j.1572-0241.2003.07591.x","article-title":"Association between physical activity, fiber intake, and other lifestyle variables and constipation in a study of women","volume":"98","author":"Dukas","year":"2003","journal-title":"Am J Gastroenterol"},{"key":"2025092109480316500_ref44","doi-asserted-by":"publisher","first-page":"895","DOI":"10.14309\/ajg.0000000000000614","article-title":"Chronic constipation in the United States: Results from a population-based survey assessing healthcare seeking and use of pharmacotherapy","volume":"115","author":"Oh","year":"2020","journal-title":"Am J Gastroenterol"}],"container-title":["Age and Ageing"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ageing\/article-pdf\/54\/9\/afaf257\/64333815\/afaf257.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ageing\/article-pdf\/54\/9\/afaf257\/64333815\/afaf257.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T13:48:09Z","timestamp":1758462489000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ageing\/article\/doi\/10.1093\/ageing\/afaf257\/8259882"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,29]]},"references-count":44,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,8,29]]}},"URL":"https:\/\/doi.org\/10.1093\/ageing\/afaf257","relation":{},"ISSN":["0002-0729","1468-2834"],"issn-type":[{"value":"0002-0729","type":"print"},{"value":"1468-2834","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,9]]},"published":{"date-parts":[[2025,8,29]]},"article-number":"afaf257"}}