{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:26:58Z","timestamp":1790008018196,"version":"4.0.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["U54NS065736"],"award-info":[{"award-number":["U54NS065736"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We aimed to describe the clinical features of patients with pure autonomic failure (PAF) preceding phenoconversion that could be useful as predictive markers for advancing \u03b1-synuclein-associated neurodegeneration of the brain.<\/jats:p>\n                  <jats:p>Patients diagnosed with PAF were evaluated at eight centres (seven US-based and one European) and enrolled in a longitudinal observational cohort study (NCT01799915). Subjects underwent detailed assessments of motor, sleep, olfactory, cognitive and autonomic function and were followed prospectively to determine whether they developed parkinsonism or dementia for up to 10 years. We identified incident cases of Parkinson's disease (PD), dementia with Lewy bodies (DLB) or multiple system atrophy (MSA) and computed hazard ratios for phenoconversion as functions of clinical features.<\/jats:p>\n                  <jats:p>A total of 209 participants with PAF with a median disease duration of 6 years (IQR: 3\u201310) were enrolled. Of those, 149 provided follow-up information at an office or telemedicine visit. After a mean follow-up duration of 3 years, 48 (33%) participants phenoconverted (42% to PD, 35% to DLB and 23% to MSA). Faster phenoconversion from study enrolment to any diagnosis was associated with urinary and sexual dysfunction [hazard ratio (HR) 5.9, 95% confidence interval (CI): 1.6\u201322 and HR: 3.6, 95% CI: 1.1\u201312] followed by subtle motor signs (HR: 2.7, 95% CI: 1.2\u20136), trouble swallowing (HR 2.5, 95% CI: 1.4\u20134.5) and changes in speech (HR:2.4, 95% CI:1.1\u20134.8) at enrolment. Subjects reporting deterioration of handwriting were more likely to phenoconvert to PD (HR: 2.6, 95% CI: 1.1\u20135.9) and those reporting difficulty handling utensils were more likely to phenoconvert to DLB (HR: 6.8, 95% CI: 1.2\u201338). Patients with a younger age of PAF onset (HR: 11, 95% CI: 2.6\u201346), preserved olfaction (HR: 8.7, 95% CI: 1.7\u201345), anhidrosis (HR: 1.8, 95% CI: 1\u20133.1, P = 0.042) and severe urinary problems (HR 1.6, 95% CI: 1\u20132.5, P = 0.033) were more likely to phenoconvert to MSA. The best autonomic predictor of PD was a blunted heart rate increase during the tilt-table test (HR: 6.1, 95% CI: 1.4\u201326).<\/jats:p>\n                  <jats:p>Patients with PAF have an estimated 12% (95% CI: 9\u201315%) per year annual risk following study entry of phenoconverting to a manifest CNS synucleinopathy.<\/jats:p>","DOI":"10.1093\/brain\/awae033","type":"journal-article","created":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T17:19:20Z","timestamp":1707844760000},"page":"2440-2448","source":"Crossref","is-referenced-by-count":36,"title":["Phenoconversion in pure autonomic failure: a multicentre prospective longitudinal cohort study"],"prefix":"10.1093","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1330-3321","authenticated-orcid":false,"given":"Patricio","family":"Millar Vernetti","sequence":"first","affiliation":[{"name":"Department of Neurology, New York University Grossman School of Medicine , New York, NY 10016 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Norcliffe-Kaufmann","sequence":"additional","affiliation":[{"name":"Department of Neurology, New York University Grossman School of Medicine , New York, NY 10016 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1345-6774","authenticated-orcid":false,"given":"Jose-Alberto","family":"Palma","sequence":"additional","affiliation":[{"name":"Department of Neurology, New York University Grossman School of Medicine , New York, NY 10016 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Italo","family":"Biaggioni","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University , Nashville, TN 37232 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyndya A","family":"Shibao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University , Nashville, TN 37232 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Peltier","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University , Nashville, TN 37232 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy","family":"Freeman","sequence":"additional","affiliation":[{"name":"Department of Neurology , Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Gibbons","sequence":"additional","affiliation":[{"name":"Department of Neurology , Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5709-9940","authenticated-orcid":false,"given":"David S","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Autonomic Medicine Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, MD 20892 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip A","family":"Low","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1263-6850","authenticated-orcid":false,"given":"Wolfgang","family":"Singer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1206-0222","authenticated-orcid":false,"given":"Elizabeth A","family":"Coon","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8488-0313","authenticated-orcid":false,"given":"Mitchell G","family":"Miglis","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University , Palo Alto, CA 94304 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor K","family":"Wenning","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Innsbruck , Innsbruck, 6020 , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2854-4179","authenticated-orcid":false,"given":"Alessandra","family":"Fanciulli","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Innsbruck , Innsbruck, 6020 , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Vernino","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Texas Southwestern , Dallas, TX 75390 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca A","family":"Betensky","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Global Public Health, New York University , New York, NY 10003 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1851-9981","authenticated-orcid":false,"given":"Horacio","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Department of Neurology, New York University Grossman School of Medicine , New York, NY 10016 , 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