{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T23:32:21Z","timestamp":1777851141506,"version":"3.51.4"},"reference-count":51,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T00:00:00Z","timestamp":1770422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T00:00:00Z","timestamp":1770422400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U19AG024904"],"award-info":[{"award-number":["U19AG024904"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"St. Michaels Hospital Foundation Heather and Eric Donnelly endowment"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Geriatr Psychiatry Neurol"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Psychosis is a significant neuropsychiatric symptom in Alzheimer\u2019s Disease (AD) and Mild Cognitive Impairment (MCI). While female APOE4 homozygotes are at the highest risk of psychosis, mechanisms underlying this association remain unclear. We investigated whether epigenetic age acceleration (EAA) is associated with psychosis in individuals with AD and MCI, and whether this association varies by sex and APOE4 status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Participants with clinical MCI or AD were drawn from the Alzheimer\u2019s Disease Neuroimaging Initiative database. EAA was calculated from DNA methylation data using the PhenoAge epigenetic clock, with the Horvath and Hannum clocks included for comparison. Psychosis status was defined as experiencing hallucinations or delusions at any time, based on the Neuropsychiatric Inventory Questionnaire. Logistic regression models were used to assess associations between EAA and psychosis, including three-way interactions with sex and APOE4 carrier status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 418 total participants (54 with psychosis, 84 female APOE4 carriers), EAA was not associated with psychosis for any of the 3 clocks utilized. However, a significant three-way interaction between sex, APOE4 carrier status, and PhenoAge EAA in predicting psychosis was observed (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.013). Elevated PhenoAge EAA was associated with higher odds of psychosis in female APOE4 carriers (OR = 1.76 per 5-year,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .025), whereas no associations were observed for other subgroups or clocks.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PhenoAge EAA may serve as a novel biomarker of psychosis among female APOE4 carriers. These findings highlight the potential of second-generation epigenetic clocks for early risk stratification and biological investigations into psychosis in AD and MCI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/08919887261424535","type":"journal-article","created":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T19:22:42Z","timestamp":1770492162000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Peripheral Blood Epigenetic Age Acceleration is Associated With Psychosis in Female APOE4 Carriers With Mild Cognitive Impairment and Alzheimer\u2019s Disease: A Pilot Study"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8051-1156","authenticated-orcid":false,"given":"Dylan","family":"Kwan","sequence":"first","affiliation":[{"name":"St. Michael\u2019s Hospital"},{"name":"McMaster University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neda","family":"Rashidi-Ranjbar","sequence":"additional","affiliation":[{"name":"St. Michael\u2019s Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph E.","family":"Marinas","sequence":"additional","affiliation":[{"name":"University of Toronto"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Namasivayam","sequence":"additional","affiliation":[{"name":"University of Toronto"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan","family":"Churchill","sequence":"additional","affiliation":[{"name":"St. Michael\u2019s Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis R.","family":"Fornazzari","sequence":"additional","affiliation":[{"name":"St. Michael\u2019s Hospital"},{"name":"University of Toronto"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5529-3731","authenticated-orcid":false,"given":"Zahinoor","family":"Ismail","sequence":"additional","affiliation":[{"name":"University of Calgary"},{"name":"University of Calgary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"DeLuca","sequence":"additional","affiliation":[{"name":"St. Michael\u2019s Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom A.","family":"Schweizer","sequence":"additional","affiliation":[{"name":"St. Michael\u2019s Hospital"},{"name":"University of Toronto"},{"name":"University of Toronto"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David G.","family":"Munoz","sequence":"additional","affiliation":[{"name":"St. Michael\u2019s Hospital"},{"name":"St. Michael\u2019s Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinne E.","family":"Fischer","sequence":"additional","affiliation":[{"name":"St. Michael\u2019s Hospital"},{"name":"University of Toronto"},{"name":"University of Toronto"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"For the Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,2,7]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2013.08.020"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.15m10617"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102431"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1159\/000339954"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.2217\/nmt.12.19"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.3928\/00989134-20090706-05"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24135"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1177\/08919887241313225"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci12091266"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.2174\/1567205014666170220150021"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/YCO.0000000000000699"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11682-013-9272-x"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101348"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-10-r115"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.10.016"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101414"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/schizbullopen\/sgac030"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100864"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.2217\/epi-2022-0209"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44400-025-00007-1"},{"key":"e_1_3_5_22_2","unstructured":"ADNI documentation \u2013 cohorts. Accessed January 22 2026.https:\/\/adni.loni.usc.edu\/quick-start-guide-asset101625\/cohorts.html"},{"key":"e_1_3_5_23_2","first-page":"26","article-title":"Alzheimer\u2019s disease neuroimaging initiative. A cross-sectional analysis of APOE gene polymorphism and the risk of cognitive impairments in the alzheimer\u2019s disease neuroimaging initiative study","volume":"10","author":"Wang G","year":"2021","unstructured":"Wang G, Vance DE, Li W. Alzheimer\u2019s disease neuroimaging initiative. A cross-sectional analysis of APOE gene polymorphism and the risk of cognitive impairments in the alzheimer\u2019s disease neuroimaging initiative study. JAR Life. 2021;10:26-31.","journal-title":"JAR Life"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2024.02.013"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1177\/0891988719882102"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1176\/jnp.12.2.233"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/1099-1166(200102)16:2<123::AID-GPS260>3.0.CO;2-1"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-021-00597-3"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu049"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btaa825"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-018-0004-3"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1177\/2633105520942221"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-210517"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.3233\/CH-131745"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-016-0397-2"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.7762\/cnr.2018.7.4.229"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1159\/000343302"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells13060485"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-025-01548-3"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2020.172981"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells14040243"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2008.04.001"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.045098"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1604558113"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1041610200006657"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1177\/0706743716648296"},{"issue":"12","key":"e_1_3_5_47_2","first-page":"CD013304","article-title":"Antipsychotics for agitation and psychosis in people with Alzheimer\u2019s disease and vascular dementia","volume":"12","author":"M\u00fchlbauer V","year":"2021","unstructured":"M\u00fchlbauer V, M\u00f6hler R, Dichter MN, Zuidema SU, K\u00f6pke S, Luijendijk HJ. Antipsychotics for agitation and psychosis in people with Alzheimer\u2019s disease and vascular dementia. Cochrane Database Syst Rev. 2021;12(12):CD013304.","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202913"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13028"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1041610217000874"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-190828"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jagp.2020.09.002"}],"container-title":["Journal of Geriatric Psychiatry and Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/08919887261424535","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/08919887261424535","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/08919887261424535","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:17:24Z","timestamp":1777501044000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/08919887261424535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,7]]},"references-count":51,"alternative-id":["10.1177\/08919887261424535"],"URL":"https:\/\/doi.org\/10.1177\/08919887261424535","relation":{},"ISSN":["0891-9887","1552-5708"],"issn-type":[{"value":"0891-9887","type":"print"},{"value":"1552-5708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,7]]},"article-number":"08919887261424535"}}