{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:40:24Z","timestamp":1787841624431,"version":"build-2784847793"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Dysautonomia affects many patients with Parkinson's disease and correlates with increased cardiovascular mortality. We describe the frequency and onset time of autonomic dysfunction relative to disease onset in early\u2010onset Parkinson's disease (EOPD) and explore its association with mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We identified all incident Parkinson cases with motor\u2010symptom onset before age 50\u2009years evaluated at the Mayo Clinic Health System (1990\u20132022) including sex\u2010 and age\u2010matched controls for each patient. Medical record review confirmed clinical diagnosis and assessed the presence and onset of autonomic symptoms, relative to Parkinson onset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We included 829 patients with EOPD and 829 healthy controls. The median age at disease onset was 42\u2009years (interquartile range [IQR]\u2009=\u200937\u201346\u2009years). Autonomic symptoms were present in 63.4% of patients, compared with 27.0% of unaffected controls, and proceeded motor symptoms in 91.4%. Forty\u2010seven percent of patients with early\u2010onset Parkinson's disease had constipation, 27.4% had bladder urgency, 19.3% had orthostatic intolerance, and 15.4% had sweat dysfunction. Among male patients, 36.8% had erectile dysfunction. In our EOPD population only, the presence of any autonomic\u2010impairment symptoms correlated with a 2.71\u2010fold increased mortality risk; each additional reported symptom increased the relative mortality risk by 50% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Patients with constipation or orthostatic intolerance had a 3.22\u2010 and 2.78\u2010fold higher mortality than patients without these symptoms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Autonomic impairment affects 63.4% of patients with EOPD and carries a 3\u2010fold higher mortality risk, which increases with every additional autonomic symptom reported. In our cohort, autonomic symptoms appeared most commonly after motor onset, contrasting with prodromal autonomic impairment seen in late\u2010onset Parkinson's disease (LOPD). ANN NEUROL 2026;99:964\u2013975<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78143","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:59:41Z","timestamp":1767182381000},"page":"964-975","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Autonomic Dysfunction and Risk of Mortality in Early\u2010Onset Parkinson's Disease"],"prefix":"10.1002","volume":"99","author":[{"given":"Capucine","family":"Piat","sequence":"first","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester MN"},{"name":"Department of Neurology Nantes University Hospital  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aidan F.","family":"Mullan","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Research Mayo Clinic  Rochester 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