{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T18:02:39Z","timestamp":1793988159924,"version":"4.8.0"},"reference-count":73,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2025,8]]},"abstract":"Abstract<\/jats:title>\n \n INTRODUCTION<\/jats:title>\n The presence and interaction of multiple comorbid neuropathologies are a major contributor to the worldwide dementia burden.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n We analyzed 1183 subjects from the National Alzheimer's Coordinating Center dataset with various combinations of isolated and mixed neurodegenerative pathologies and conducted mixed\u2010effects multiple linear regression modeling to comprehensively compare the neurocognitive and neuropsychological trajectories between groups over time.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n In combination with Alzheimer's disease neuropathologic change, various combinations of limbic\u2010predominant age\u2010related transactive response DNA\u2010binding protein 43 encephalopathy, Lewy body dementia, and cerebrovascular disease further impair global cognition and specific neurocognitive domains; however, they do not appear to extensively affect the rate of decline with time across these domains, suggesting an additive but not synergistic effect.<\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n These findings corroborate the known cumulative effects of mixed pathologies on cognition and add nuance to our understanding of their specific interactions, which is crucial for the development of biomarkers and effective therapeutics.<\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n Mixed neurodegenerative pathologies are common in the elderly population.<\/jats:p>\n <\/jats:list-item>\n \n The most common neurodegenerative pathologies were Alzheimer's disease neuropathologic change (ADNC), cerebrovascular disease (CVD), Lewy body dementia (LBD), and limbic\u2010predominant age\u2010related transactive response DNA\u2010binding protein 43 encephalopathy (LATE).<\/jats:p>\n <\/jats:list-item>\n \n The addition of various combinations of comorbid CVD, LBD, and LATE to ADNC worsened overall performance on cognitive and neuropsychological testing across time.<\/jats:p>\n <\/jats:list-item>\n \n \n In general, the addition of multiple comorbid neurodegenerative pathologies did not influence the\n rate<\/jats:italic>\n of decline across the evaluated time period.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.70575","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T06:45:56Z","timestamp":1754376356000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Cognitive and neuropsychological trajectories in patients with mixed neurodegenerative pathologies"],"prefix":"10.1002","volume":"21","author":[{"given":"Francisco C.","family":"Almeida","sequence":"first","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine University of Minho, Campus Gualtar Braga Portugal"},{"name":"ICVS\/3B's\u2010PT Government Associate Laboratory University of Minho, Campus Gualtar Braga Portugal"},{"name":"Department of Neuroradiology Centro Hospitalar Universit\u00e1rio do Porto Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel A.","family":"Marx","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular and Cell\u2010Based Medicine Icahn School of Medicine at Mount Sinai New York New York USA"},{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai New York New York USA"},{"name":"Nash Family Department of Neuroscience Icahn School of Medicine at Mount Sinai New York New York USA"},{"name":"Department of Artificial Intelligence & Human Health Icahn School of Medicine at Mount Sinai New York New York USA"},{"name":"Ronald M. 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