{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:28:10Z","timestamp":1792506490840,"version":"4.5.0"},"reference-count":45,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2023,5,1]]},"abstract":"<jats:sec id=\"ab-noi230006-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Cross-sectional evidence implicates high prevalent frailty in patients with Parkinson disease (PD), whereas the longitudinal association remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi230006-5\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To examine the longitudinal association of the frailty phenotype with the development of PD and to explore the modification role of genetic risk of PD in such an association.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi230006-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>This prospective cohort study launched in 2006 to 2010 with a follow-up of 12 years. Data were analyzed from March 2022 to December 2022. The UK Biobank recruited over 500\u202f000 middle-aged and older adults from 22 assessment centers across the United Kingdom. Participants who were younger than 40 years (n\u2009=\u2009101), diagnosed with dementia or PD at baseline, and developed dementia, PD, or died within 2 years from baseline were excluded (n\u2009=\u20094050). Participants who had no genetic data or mismatch between genetic sex and reported gender (n\u2009=\u200915\u202f350), were not of self-reported British White descent (n\u2009=\u200927\u202f850), and had no data for frailty assessment (n\u2009=\u2009100\u202f450) or any covariates were also excluded (n\u2009=\u200939\u202f706). The final analysis included 314\u202f998 participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi230006-7\">\n                    <jats:title>Exposures<\/jats:title>\n                    <jats:p>The physical frailty was assessed by the Fried criteria\u2019s frailty phenotype through 5 domains, ie, weight loss, exhaustion, low physical activity, slow walking speed, and low grip strength. The polygenic risk score (PRS) for PD comprised 44 single-nucleotide variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi230006-8\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>New-onset PD was identified through the hospital admission electronic health records and death register.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi230006-9\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 314\u202f998 participants (mean age, 56.1 years; 49.1% male), 1916 new-onset PD cases were documented. Compared with nonfrailty, the hazard ratio (HR) of incident PD in prefrailty and frailty was 1.26 (95% CI, 1.15-1.39) and 1.87 (95% CI, 1.53-2.28), respectively, and the absolute rate difference per 100\u202f000 person-years was 1.6 (95% CI, 1.0-2.3) for prefrailty and 5.1 (95% CI, 2.9-7.3) for frailty. Exhaustion (HR, 1.41; 95% CI, 1.22-1.62), slow gait speed (HR, 1.32; 95% CI, 1.13-1.54), low grip strength (HR, 1.27; 95% CI, 1.13-1.43), and low physical activity (HR, 1.12; 95% CI, 1.00-1.25) were associated with incident PD. A significant interaction between frailty and PRS on PD was found and the highest hazard was observed in participants with frailty and high genetic risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-noi230006-10\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>Physical prefrailty and frailty were associated with incident PD independent of sociodemographic factors, lifestyles, multiple morbidities, and genetic background. These findings may have implications for the assessment and management of frailty for PD prevention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaneurol.2023.0183","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T11:07:22Z","timestamp":1678705642000},"page":"455","source":"Crossref","is-referenced-by-count":97,"title":["Physical Frailty, Genetic Predisposition, and Incident Parkinson Disease"],"prefix":"10.1001","volume":"80","author":[{"given":"Zekun","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"},{"name":"Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 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