{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T16:57:42Z","timestamp":1789750662813,"version":"4.0.1"},"reference-count":70,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R012RF1AG025516"],"award-info":[{"award-number":["R012RF1AG025516"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG067018"],"award-info":[{"award-number":["R01AG067018"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P01AG025204"],"award-info":[{"award-number":["P01AG025204"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG085566"],"award-info":[{"award-number":["R01AG085566"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG063752"],"award-info":[{"award-number":["R01AG063752"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003653","name":"Korea National Institute of Health","doi-asserted-by":"publisher","award":["2024\u2010ER0505\u201000"],"award-info":[{"award-number":["2024\u2010ER0505\u201000"]}],"id":[{"id":"10.13039\/501100003653","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Altered glymphatic\u2010related fluid dynamics are increasingly recognized as a feature of Alzheimer's disease (AD). We generalized an established diffusion imaging framework to quantify periventricular diffusivity (PVeD), hypothesizing that fast diffusion signals in the periventricular region can reflect amyloid beta (A\u03b2) deposition across the AD continuum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Participants from two multi\u2010site cohorts (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0440 and 414), comprising cognitively unimpaired individuals, those with mild cognitive impairment, and patients with AD, were included. We tested and validated the association of PVeD with A\u03b2 burden and core AD characteristics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Lower PVeD was extensively associated with greater A\u03b2 burden, neurodegeneration, cognitive impairment, and clinical severity in the clinical cohort. Importantly, the relationship between PVeD and A\u03b2 burden was significantly modulated by apolipoprotein E (\n                      <jats:italic>APOE<\/jats:italic>\n                      ) \u03b54 status;\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 carriers exhibited a replicable stronger negative association. Baseline PVeD also predicted longitudinal cognitive decline.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      These findings suggest that periventricular diffusion signals reflect\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54\u2013modulated A\u03b2 burden and cognitive decline in AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>An automated method for quantifying periventricular diffusivity (PVeD) is developed.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Lower PVeD is associated with higher amyloid load only in a mild cognitive impairment\u2013dominant cohort.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Higher amyloid burden may mediate the link between lower PVeD and poorer cognitive outcomes in the clinical cohort.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Apolipoprotein E \u03b54 carriers show a reproducibly stronger inverse PVeD\u2014amyloid association than non\u2010carriers.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Baseline PVeD can predict longitudinal Mini\u2010Mental State Examination decline in two independent cohorts.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70659","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T13:25:33Z","timestamp":1758201933000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Periventricular diffusivity reflects\n                    <i>APOE<\/i>\n                    \u03b54\u2013modulated amyloid accumulation and cognitive impairment in the Alzheimer's disease continuum"],"prefix":"10.1002","volume":"21","author":[{"given":"Chang\u2010Le","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Bioengineering University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Joon","family":"Son","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Ajou University School of Medicine  Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah","family":"Schweitzer","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hecheng","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linghai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaolin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Pittsburgh  Pittsburgh Pennsylvania USA"},{"name":"Department of Psychiatry University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang Hyung","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Ajou University School of Medicine  Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Woong","family":"Roh","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Ajou University School of Medicine  Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bumhee","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics Ajou University School of Medicine  Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Wook","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Radiology Ajou University School of Medicine  Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young\u2010Sil","family":"An","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Molecular Imaging Ajou University School of Medicine  Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Woon","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Neurology Samsung Medical Centre Sungkyunkwan University School of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Hyuk","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Ajou University School of Medicine  Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunhwa","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Ajou University School of Medicine  Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You Jin","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Ajou University School of Medicine  Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davneet S.","family":"Minhas","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles M.","family":"Laymon","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Pittsburgh  Pittsburgh Pennsylvania USA"},{"name":"Department of Radiology University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George D.","family":"Stetten","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana L.","family":"Tudorascu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"},{"name":"Department of Biostatistics University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard J.","family":"Aizenstein","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Pittsburgh  Pittsburgh Pennsylvania USA"},{"name":"Department of Psychiatry University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjie","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Mayo Clinic Study of Aging","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01296-0"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2022.105986"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(18)30318\u20101"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.26892"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab428"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010020\u20100731\u20107"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2019.0572"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2022.119329"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003748"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP277635"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0244442"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12987\u2010021\u201000282\u2010z"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104987"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2020.04.003"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00031.2020"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.827398"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.844938"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13139\u2010020\u201000665\u20104"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2021204088"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.5162"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.2463\/mrms.rev.2020\u20100122"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.28977"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20230016"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.04.070"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11604\u2010017\u20100617\u2010z"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/jon.12837"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2023.0321\u20102"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00234-023-03270-2"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.2463\/mrms.rev.2023\u20100175"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13789"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14149"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.042259"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-024-01598-2"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1159\/000115751"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181f11d85"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.091346"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giae049"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2001.0978"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14094"},{"key":"e_1_2_10_41_1","first-page":"332","article-title":"The use of Centiloids for applying [11C] PiB classification cutoffs across region\u2010of\u2010interest delineation methods","volume":"10","author":"Tudorascu DL","year":"2018","journal-title":"Alzheimer's Dement"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.08.005"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.06.021"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1109\/TMI.2010.2045126"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.05.027"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.10.009"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.093872"},{"key":"e_1_2_10_48_1","volume-title":"Statistical parametric mapping: the analysis of functional brain images","author":"Penny WD","year":"2011"},{"issue":"1","key":"e_1_2_10_49_1","first-page":"8","article-title":"A validity study of K\u2010MMSE as a screening test for dementia: comparison against a comprehensive neuropsychological evaluation","volume":"9","author":"Oh E\u2010A","year":"2010","journal-title":"Dement Neurocognit Disorder"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.65.8.1091"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2010.25.7.1071"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.12779\/dnd.2023.22.1.1"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2013.12.040"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.55.10.967"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1162\/imag_a_00306"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.08.047"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.11.024"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000201300"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2012.263"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.11.013"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-221016"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1186\/s42466-021-00102-7"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI169131"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI171838"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002156"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010020\u20100312\u2010z"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20160381"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26364"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13629"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-024-00673-7"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2022.03.006"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70659","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.70659","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70659","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T11:08:22Z","timestamp":1771153702000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.70659"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":70,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/alz.70659"],"URL":"https:\/\/doi.org\/10.1002\/alz.70659","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"2025-05-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70659"}}