{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:45:31Z","timestamp":1792813531625,"version":"4.5.0"},"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["PJT-173540"],"award-info":[{"award-number":["PJT-173540"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Queen Elizabeth II Graduate Scholarship in Science & Technology"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Cognitive impairment is a common non-motor symptom of Parkinson\u2019s disease (PD), yet its underlying mechanisms remain poorly understood.\n                      <jats:italic>Apolipoprotein E4 (APOE4)<\/jats:italic>\n                      , a genetic risk factor of Alzheimer\u2019s Disease, has been associated with PD-related cognitive impairment. However, findings are inconsistent, highlighting the need for further investigation. Neuroimaging studies have found gray matter abnormalities, mainly reductions in gray matter volume (GMV) and cortical thickness (CTh), in both cognitively impaired PD patients and\n                      <jats:italic>APOE4<\/jats:italic>\n                      carriers. Yet,\n                      <jats:italic>APOE4\u2019s<\/jats:italic>\n                      role in these structural changes and their cognitive impact in PD is underexplored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      This study aimed to determine whether\n                      <jats:italic>APOE4<\/jats:italic>\n                      influences early structural brain differences in terms of GMV and CTh in PD prior to the emergence of cognitive dysfunction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 51 PD\n                      <jats:italic>APOE4<\/jats:italic>\n                      carriers and 120 non-carriers who were cognitively unimpaired from the Parkinson\u2019s Progression Markers Initiative (PPMI) database were included. T1-weighted MRI scans were used to calculate GMV and CTh in regions previously associated with PD-related cognitive impairment, including hippocampal subregions. Cognitive scores assessing global cognition and specific cognitive domains were used to examine associations between regions showing significant GMV or CTh group differences and cognitive performance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PD\n                      <jats:italic>APOE4<\/jats:italic>\n                      carriers showed increased GMV in the left angular gyrus (AnG) and decreased GMV in the left nucleus accumbens (NAcc) compared to non-carriers, though neither survived multiple comparison correction. Left AnG GMV correlated with visuospatial function in both groups but did not remain significant after co-variate adjustment. Left NAcc GMV correlated with visuospatial function and working memory, but only in non-carriers even after co-variate adjustment. No group differences were observed in CTh measures and hippocampal subregion GMVs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study suggests that\n                      <jats:italic>APOE4<\/jats:italic>\n                      may not influence cognitive function in PD by affecting GMV and CTh. However, longitudinal analyses must confirm these observations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0341240","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T18:38:35Z","timestamp":1768934315000},"page":"e0341240","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["The effect of Apolipoprotein E4 on cognitive function in Parkinson\u2019s disease: A structural MRI study in the PPMI cohort"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1198-1306","authenticated-orcid":true,"given":"Angenelle 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