@article{0e6b29a85dc545e3805a16dc49e69add,
title = "Lysosomal Polygenic Burden Drives Cognitive Decline in Parkinson's Disease with Low Alzheimer Risk",
abstract = "Background: 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. Objectives: To assess the influence of lysosomal polygenic burden on cognitive progression in Parkinson's disease patients with low Alzheimer's disease risk. Methods: Using Cox regression we assessed association between lysosomal polygenic scores and time to Montreal Cognitive Assessment score ≤ 21 in the Parkinson's Progression Markers Initiative cohort (n = 374), with replication in data from the Parkinson's Disease Biomarker Program (n = 777). Patients were stratified by Alzheimer's disease polygenic risk. Results: The lysosomal polygenic score was associated with faster progression of cognitive decline in patients with low Alzheimer's disease risk in both datasets (P = 0.0032 and P = 0.0054, respectively). Conclusion: Our study supports complex interplay between genetics and neuropathology in Parkinson's disease-related cognitive impairment, emphasizing the role of lysosomal polygenic burden.",
keywords = "Parkinson's disease, cognition, lysosomal pathway, neuropathology, polygenic risk score",
author = "Jon-Anders Tunold and Tan, {Manuela M X} and Mathias Toft and Owen Ross and {van de Berg}, {Wilma D J} and Lasse Pihlstr{\o}m",
note = "Funding Information: M.T. and L.P. have recieved grants from the South‐Eastern Regional Health Authority, Norway. W.B. has received funding from the Dutch Parkinson association, Health Holland, and Rotary Club Aalsmeer‐Uithoorn. O.R. is supported by NIH (RF1 NS085070; U54‐NS100693; U01 NS100620; R01 AG056366; U19 AG071754), DOD (W81XWH‐17‐1‐0249), The Michael J. Fox Foundation, The Little Family Foundation, the Mayo Clinic Dorothy and Harry T. Mangurian Jr. Lewy Body Dementia Program at Mayo Clinic, Ted Turner and family with the Functional Genomics of LBD Program and the Mayo Clinic LBD Center without Walls (U54‐NS110435). Mayo Clinic (O.R.) was a recipient of the inaugural Cure One, Cure Many Award from the American Brain Foundation for the study of Lewy body dementia. Mayo Clinic is an American Parkinson Disease Association (APDA) Mayo Clinic Information and Referral Center, an APDA Center for Advanced Research, and a Lewy Body Dementia Association Research Center of Excellence. Publisher Copyright: {\textcopyright} 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.",
year = "2023",
month = dec,
day = "20",
doi = "https://doi.org/10.1002/mds.29698",
language = "English",
journal = "Movement disorders",
issn = "0885-3185",
publisher = "John Wiley and Sons Inc.",
}