{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T04:12:17Z","timestamp":1793160737762,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:00:00Z","timestamp":1703030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Genetics influence cognitive progression in Parkinson's disease, possibly through mechanisms related to Lewy and Alzheimer's disease pathology. Lysosomal polygenic burden has recently been linked to more severe Lewy pathology post mortem.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To assess the influence of lysosomal polygenic burden on cognitive progression in Parkinson's disease patients with low Alzheimer's disease risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using Cox regression we assessed association between lysosomal polygenic scores and time to Montreal Cognitive Assessment score\u2009\u2264\u200921 in the Parkinson's Progression Markers Initiative cohort (n\u2009=\u2009374), with replication in data from the Parkinson's Disease Biomarker Program (n\u2009=\u2009777). Patients were stratified by Alzheimer's disease polygenic risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The lysosomal polygenic score was associated with faster progression of cognitive decline in patients with low Alzheimer's disease risk in both datasets (<jats:italic>P<\/jats:italic>\u2009=\u20090.0032 and <jats:italic>P<\/jats:italic>\u2009=\u20090.0054, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study supports complex interplay between genetics and neuropathology in Parkinson's disease\u2010related cognitive impairment, emphasizing the role of lysosomal polygenic burden. \u00a9 2023 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.29698","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T01:50:20Z","timestamp":1703123420000},"page":"596-601","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Lysosomal Polygenic Burden Drives Cognitive Decline in Parkinson's Disease with Low Alzheimer Risk"],"prefix":"10.1002","volume":"39","author":[{"given":"Jon\u2010Anders","family":"Tunold","sequence":"first","affiliation":[{"name":"Department of Neurology Oslo University Hospital  Oslo Norway"},{"name":"Institute of Clinical Medicine University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela M.X.","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Neurology Oslo University Hospital  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Toft","sequence":"additional","affiliation":[{"name":"Department of Neurology Oslo University Hospital  Oslo Norway"},{"name":"Institute of Clinical Medicine University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4813-756X","authenticated-orcid":false,"given":"Owen","family":"Ross","sequence":"additional","affiliation":[{"name":"Mayo Clinic, Department of Neuroscience  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilma D.J.","family":"van de Berg","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurosciences Amsterdam UMC, Vrije Universiteit  Amsterdam The Netherlands"},{"name":"Amsterdam Neuroscience, Program Neurodegeneration  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7635-8645","authenticated-orcid":false,"given":"Lasse","family":"Pihlstr\u00f8m","sequence":"additional","affiliation":[{"name":"Department of Neurology Oslo University Hospital  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21956"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp245"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00280-3"},{"issue":"11","key":"e_1_2_9_5_1","first-page":"1234","article-title":"Neuropathology of dementia in patients with Parkinson's disease: a systematic review of autopsy studies","volume":"90","author":"Smith C","year":"2019","journal-title":"J Neurol Neurosurg 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