{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T18:02:38Z","timestamp":1793988158393,"version":"4.8.0"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:00:00Z","timestamp":1738195200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30AG072975"],"award-info":[{"award-number":["P30AG072975"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30AG010161"],"award-info":[{"award-number":["P30AG010161"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG067482"],"award-info":[{"award-number":["R01 AG067482"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG015819"],"award-info":[{"award-number":["R01AG015819"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG017917"],"award-info":[{"award-number":["R01AG017917"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG064233"],"award-info":[{"award-number":["R01AG064233"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG022018"],"award-info":[{"award-number":["R01AG022018"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG056405"],"award-info":[{"award-number":["R01AG056405"]}],"id":[{"id":"10.13039\/100000002","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":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>This study investigates the inter\u2010related roles of hippocampal neuronal loss (HNL), limbic\u2010predominant age\u2010related TAR\u2010DNA binding protein of 43 kDa (TDP\u201043) encephalopathy neuropathologic changes (LATE\u2010NC), and Alzheimer's disease neuropathologic changes (ADNC) on cognitive decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Participants underwent annual cognitive testing and autopsy. HNL, ADNC, LATE\u2010NC, and other age\u2010related pathologies were evaluated. Regression and mixed\u2010effects models examined the association of HNL with ADNC and LATE\u2010NC, and separately with cognitive decline. Path analyses examined the extent to which associations of LATE\u2010NC and ADNC with cognitive decline were attributable to HNL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>LATE\u2010NC was associated with more severe HNL, but ADNC was associated only after excluding subjects with hippocampal sclerosis (HS). HNL was associated with faster decline in global cognition and episodic, semantic, and working memory. In path analyses, about 61% of the association of LATE\u2010NC with cognitive decline was attributable to HNL, whereas for ADNC it was mostly independent of HNL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>HNL has an independent contribution to cognitive decline and acts as a major step in LATE\u2010NC\u2010related cognitive decline.<\/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>Hippocampal neuronal loss (HNL) is associated with cognitive decline.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>HNL is a prominent feature of limbic\u2010predominant age\u2010related TDP\u201043 encephalopathy neuropathologic changes (LATE\u2010NC) and less so with Alzheimer's disease neuropathologic changes (ADNC).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>HNL acts as a major pathway in cognitive decline for LATE\u2010NC.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Differential mechanisms in hippocampal degeneration are associated with LATE\u2010NC versus ADNC.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14500","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T04:44:51Z","timestamp":1738212291000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Hippocampal neuronal loss and cognitive decline in LATE\u2010NC and ADNC among community\u2010dwelling older persons"],"prefix":"10.1002","volume":"21","author":[{"given":"Sonal","family":"Agrawal","sequence":"first","affiliation":[{"name":"Rush Alzheimer's Disease Center Rush University Medical Center  Chicago Illinois USA"},{"name":"Department of Pathology Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yu","sequence":"additional","affiliation":[{"name":"Rush Alzheimer's Disease Center Rush University Medical Center  Chicago Illinois USA"},{"name":"Department of Neurological Sciences Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue E.","family":"Leurgans","sequence":"additional","affiliation":[{"name":"Rush Alzheimer's Disease Center Rush University Medical Center  Chicago Illinois USA"},{"name":"Department of Neurological Sciences Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukriti","family":"Nag","sequence":"additional","affiliation":[{"name":"Rush Alzheimer's Disease Center Rush University Medical Center  Chicago Illinois USA"},{"name":"Department of Pathology Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa L","family":"Barnes","sequence":"additional","affiliation":[{"name":"Rush Alzheimer's Disease Center Rush University Medical Center  Chicago Illinois USA"},{"name":"Department of Behavioral Sciences Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Bennett","sequence":"additional","affiliation":[{"name":"Rush Alzheimer's Disease Center Rush University Medical Center  Chicago Illinois USA"},{"name":"Department of Neurological Sciences Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A","family":"Schneider","sequence":"additional","affiliation":[{"name":"Rush Alzheimer's Disease Center Rush University Medical Center  Chicago Illinois USA"},{"name":"Department of Pathology Rush University Medical Center  Chicago Illinois USA"},{"name":"Department of Neurological Sciences Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072\u2010199704000\u201000010"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr053"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.59.7.1099"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00296500"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.3961"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlw033"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008679"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410410106"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440\u20101819.2000.00747.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-179939"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/156720512801322627"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002175"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000055863.87435.B2"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000042478.08543.F7"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.10.007"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003610"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12939"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24388"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010602"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.61.3.378"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlad086"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000207497"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30029-1"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200182"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1154-1"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2019.00099"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0905529106"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.01.022"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad8373"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.06.026"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13780"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010023\u201002606\u20109"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt273"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000324924.91351.7d"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.58.10.1476"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002923"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074069"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410270502"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1006\/brcg.2001.1500"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318200d6f9"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000200959.50898.26"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.54.4.843"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.48.1.154"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750\u20103639.2003.tb00027.x"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab092"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.66"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010171068"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz277"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab262"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.14500","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.14500","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.14500","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:41:16Z","timestamp":1789558876000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.14500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,30]]},"references-count":49,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/alz.14500"],"URL":"https:\/\/doi.org\/10.1002\/alz.14500","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,30]]},"assertion":[{"value":"2024-08-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14500"}}