{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T06:22:15Z","timestamp":1778134935255,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Parkinson's disease (PD) may result from the combined effect of multiple etiological factors. The relationship between disease incidence and age, as demonstrated in the cancer literature, can be used to model a multistep pathogenic process, potentially affording unique insights into disease development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We tested whether the observed incidence of PD is consistent with a multistep process, estimated the number of steps required and whether this varies with age, and examined drivers of sex differences in PD incidence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Our validated probabilistic modeling process, based on medication prescribing, generated nationwide age\u2010 and sex\u2010adjusted PD incidence data spanning 2006\u20132017. Models of log(incidence) versus log(age) were compared using Bayes factors, to estimate (1) if a linear relationship was present (indicative of a multistep process); (2) the relationship's slope (one less than number of steps); (3) whether slope was lower at younger ages; and (4) whether slope or <jats:italic>y<\/jats:italic>\u2010intercept varied with sex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Across &gt;15,000 incident cases of PD, there was a clear linear relationship between log(age) and log(incidence). Evidence was strongest for a model with an initial slope of 5.2 [3.8, 6.4], an inflexion point at age 45, and beyond this a slope of 6.8 [6.4, 7.2]. There was evidence for the intercept varying by sex, but no evidence for slope being sex\u2010dependent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The age\u2010specific incidence of PD is consistent with a process that develops in multiple, discrete steps \u2013 on average six before age 45 and eight after. The model supports theories emphasizing the primacy of environmental factors in driving sex differences in PD incidence. \u00a9 2021 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.28719","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T07:43:00Z","timestamp":1628581380000},"page":"2530-2538","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["A Multi\u2010Step Model of Parkinson's Disease Pathogenesis"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0618-3795","authenticated-orcid":false,"given":"Campbell","family":"Le Heron","sequence":"first","affiliation":[{"name":"New Zealand Brain Research Institute  Christchurch New Zealand"},{"name":"Department of Neurology Canterbury District 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