{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T10:09:22Z","timestamp":1787998162966,"version":"build-2784847793"},"reference-count":69,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Diffusion\u2010weighted imaging derived mean diffusivity (MD) correlates with Alzheimer's disease (AD) biomarkers, yet its neuropathological correlates remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Diffusion\u2010weighted imaging,\n                      <jats:italic>post mortem<\/jats:italic>\n                      neuropathology, and cognitive performance data were obtained from the National Alzheimer's Coordinating Center (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a097), Alzheimer's Disease Neuroimaging Initiative (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a021), and Arizona Study of Aging and Neurodegenerative Disorders (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a015). We examined MD associations with neuropathology, cognitive decline, and expression profiles of AD\u2010implicated genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Results revealed two latent variables\u2014one linked to amyloid\/tau, the other to vascular pathology\u2014explaining between 70% and 16% of MD\u2010pathology covariance, respectively. Higher MD correlated with worse cognitive performance, both cross\u2010sectionally and up to 16 years prior to death. MD was regionally associated with Thal phase, neuritic plaque density, Braak stage (temporal\/limbic), and infarcts (thalamus), and reflected gene expression patterns related to AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>In vivo MD captures distinct AD\u2010related pathologies across brain regions and relates to cognitive trajectories and gene expression.<\/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>Diffusion\u2010weighted imaging (DWI) can detect early gray matter microstructural differences in the Alzheimer's disease (AD) continuum.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Mean diffusivity (MD) is associated with tau, amyloid and vascular neuropathologies.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Thal amyloid phase and Braak tau score correlate with MD in temporal and limbic regions.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Multivariate MD scores differentially relate to proteinopathies vs. vascular damage.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            MD can serve as a non\u2010invasive biomarker to predict\n                            <jats:italic>post mortem<\/jats:italic>\n                            AD neuropathology.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71037","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T14:10:30Z","timestamp":1768399830000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Gray matter microstructure from in vivo diffusion magnetic resonance imaging reflects\n                    <i>post mortem<\/i>\n                    neuropathology severity and clinical progression of Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1164-6950","authenticated-orcid":false,"given":"Zaki","family":"Alasmar","sequence":"first","affiliation":[{"name":"Cerebral Imaging Centre Douglas Mental Health University Institute  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Department of Psychiatry McGill University  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Integrated Program in Neuroscience McGill University  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cilia","family":"Tremblay","sequence":"additional","affiliation":[{"name":"Cerebral Imaging Centre Douglas Mental Health University Institute  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Department of Psychiatry McGill University  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Banner Sun Health Research Institute  Sun City Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roqaie","family":"Moqadam","sequence":"additional","affiliation":[{"name":"Cerebral Imaging Centre Douglas Mental Health University Institute  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Department of Medicine University of Montreal  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geidy E","family":"Serrano","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute  Sun City Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G","family":"Beach","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute  Sun City Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Atri","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute  Sun City Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Su","sequence":"additional","affiliation":[{"name":"Banner Alzheimer's Institute  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer's Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yashar","family":"Zeighami","sequence":"additional","affiliation":[{"name":"Cerebral Imaging Centre Douglas Mental Health University Institute  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Department of Psychiatry McGill University  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahsa","family":"Dadar","sequence":"additional","affiliation":[{"name":"Cerebral Imaging Centre Douglas Mental Health University Institute  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Department of Psychiatry McGill University  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311\u2010021\u201001146\u2010y"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.037509"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1119"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2017.09.013"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2020.108951"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000153076.46126.E9"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010020\u201000679\u20102"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.08.047"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.25271"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac013"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac343"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2005.06.029"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010021\u201001290\u2010z"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad428"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14528"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2024.106429"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010022\u201002408\u20105"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12997"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.121.263195"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31825018f7"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010023\u201001309\u20103"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010201213"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/neup.12189"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nly049"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.21049"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nic.2005.09.008"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0b013e318191c7dd"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.10.007"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010011\u20100910\u20103"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.58.12.1791"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750\u20103639.2008.00147.x"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010006\u20100127\u2010z"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.41.4.479"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1109\/TMI.2007.906087"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1109\/42.668698"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.54294\/uvnhin"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.media.2007.06.004"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2012.09.005"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.10.019"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.116137"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1109\/TMI.2010.2046908"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2022.119634"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2019.05.008"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0236418"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/mpr.329"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1162\/imag_a_00071"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0254720"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.08.047"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxj037"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2004.07.020"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010psych\u2010113011\u2010143804"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13439"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4171"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002058"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2020.117038"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.01.021"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00338.2011"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlad026"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cccb.2022.100148"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12224"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010023\u201002321\u20107"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2018.09.027"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41374\u2010019\u20100197\u2010x"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2024.1384294"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010170061"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010018\u20100298\u20109"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhq264"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.24711"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.71037","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.71037","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.71037","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T14:51:51Z","timestamp":1785941511000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.71037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":69,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/alz.71037"],"URL":"https:\/\/doi.org\/10.1002\/alz.71037","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-05-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71037"}}