{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:17:55Z","timestamp":1790021875785,"version":"4.0.1"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T00:00:00Z","timestamp":1654560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["P50 NS053488"],"award-info":[{"award-number":["P50 NS053488"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 NS115139"],"award-info":[{"award-number":["RO1 NS115139"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["U19 AG062418"],"award-info":[{"award-number":["U19 AG062418"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000864","name":"Michael J. 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Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Using a multi\u2010cohort, discovery\u2010replication\u2010validation design, we sought new plasma biomarkers that predict which individuals with Parkinson's disease (PD) will experience cognitive decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In 108 discovery cohort PD individuals and 83 replication cohort PD individuals, we measured 940 plasma proteins on an aptamer\u2010based platform. Using proteins associated with subsequent cognitive decline in both cohorts, we trained a logistic regression model to predict which patients with PD showed fast (&gt;\u00a0=\u00a01 point drop\/year on Montreal Cognitive Assessment [MoCA]) versus slow (&lt;\u20091 point drop\/year on MoCA) cognitive decline in the discovery cohort, testing it in the replication cohort. We developed alternate assays for the top 3 proteins and confirmed their ability to predict cognitive decline \u2013 defined by change in MoCA or development of incident mild cognitive impairment (MCI) or dementia \u2013 in a validation cohort of 118 individuals with PD. We investigated the top plasma biomarker for causal influence by Mendelian randomization (MR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A model with only 3 proteins (melanoma inhibitory activity protein [MIA], C\u2010reactive protein [CRP], and albumin) separated fast versus slow cognitive decline subgroups with an area under the curve (AUC) of 0.80 in the validation cohort. The individuals with PD in the validation cohort in the top quartile of risk for cognitive decline based on this model were 4.4 times more likely to develop incident MCI or dementia than those in the lowest quartile. Genotypes at MIA single nucleotide polymorphism (SNP) rs2233154 associated with MIA levels and cognitive decline, providing evidence for MIA's causal influence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>An easily obtained plasma\u2010based predictor identifies individuals with PD at risk for cognitive decline. MIA may participate causally in development of cognitive decline. ANN NEUROL 2022;92:255\u2013269<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.26410","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T03:54:56Z","timestamp":1653018896000},"page":"255-269","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Plasma\n                    <scp>MIA<\/scp>\n                    ,\n                    <scp>CRP<\/scp>\n                    , and Albumin Predict Cognitive Decline in Parkinson's Disease"],"prefix":"10.1002","volume":"92","author":[{"given":"Junchao","family":"Shen","sequence":"first","affiliation":[{"name":"Departments of Neurology, Perelman School of Medicine University of Pennsylvania  Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noor","family":"Amari","sequence":"additional","affiliation":[{"name":"Departments of Neurology, Perelman School of Medicine University of Pennsylvania  Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Zack","sequence":"additional","affiliation":[{"name":"Departments of Neurology, Perelman School of Medicine University of Pennsylvania  Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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