{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:57:39Z","timestamp":1791928659350,"version":"4.3.4"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Alzheimer\u2019s disease (AD) is the leading cause of neurodegenerative dementia, and mixed neuropathological changes including Lewy body (LB-NC) and TDP-43 (LATE-NC) are commonly observed in patients with AD. We examined the baseline cross-sectional and longitudinal effects of these co-pathologies on cognitive and neuropsychiatric trajectories.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated 77 participants who had available autopsy data and showed intermediate to high levels of AD neuropathological change from the ADNI database. Participants were categorized based on the presence or absence of LB-NC or LATE-NC. The impact of LB-NC and LATE-NC on baseline and longitudinal clinical features was assessed using linear regression and linear mixed-effects models, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirty-eight (49.4%) had LB-NC, and 39 (50.6%) had LATE-NC. At baseline, the presence of LB-NC was not associated with cognitive function or neuropsychiatric symptoms, whereas the presence of LATE-NC was associated with better trail-making test performance and less severe sleep disturbance. Longitudinally, the presence of LB-NC was associated with faster cognitive decline in global cognitive function, memory, language, and executive function, whereas the presence of LATE-NC was associated with a slower decline in language function. Neither LB-NC nor LATE-NC influenced the longitudinal trajectory of neuropsychiatric symptoms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Among patients with pathologically confirmed AD, the presence of LB-NC accelerated cognitive decline, whereas the presence of LATE-NC was not associated with overall cognitive trajectories. Investigating comorbid pathologies is essential for prognostic stratification and the development of personalized therapeutic strategies in AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1724274","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T05:19:49Z","timestamp":1776403189000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of Lewy body and limbic-predominant TDP-43 neuropathology on cognitive and neuropsychiatric trajectory in Alzheimer\u2019s disease: a retrospective neuropathological study"],"prefix":"10.3389","volume":"18","author":[{"given":"Jarok","family":"Koo","sequence":"first","affiliation":[{"name":"Chung-Ang University College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyungjin","family":"Lee","sequence":"additional","affiliation":[{"name":"Chung-Ang University College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyeong","family":"Choi","sequence":"additional","affiliation":[{"name":"Chung-Ang University College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoungwon","family":"Baik","sequence":"additional","affiliation":[{"name":"Anam Hospital, Korea University College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mincheol","family":"Park","sequence":"additional","affiliation":[{"name":"Chung-Ang University College of Medicine","place":["Seoul, Republic of Korea"]},{"name":"Department of Neurology, Chung-Ang University College of Medicine","place":["Seoul, Republic of Korea"]},{"name":"Yonsei University College of Medicine","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1186\/s40478-021-01260-0","article-title":"The association of Lewy bodies with limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes and their role in cognition and Alzheimer\u2019s dementia in older persons.","volume":"9","author":"Agrawal","year":"2021","journal-title":"Acta Neuropathol. 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