{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T12:23:01Z","timestamp":1782994981659,"version":"3.54.5"},"reference-count":32,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:00:00Z","timestamp":1690156800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2023,8,29]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Decedents with late-life dementia are often found at autopsy to have vascular pathology, cortical Lewy bodies, hippocampal sclerosis, and\/or TDP-43 encephalopathy alone or with concurrent Alzheimer\u2019s disease (AD) lesions. Nonetheless, it is commonly believed that AD neuropathologic changes (NC) are the dominant or exclusive drivers of late-life dementia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Assess associations of end-of-life cognitive impairment with any one or any combination of five distinct NC. Assess impairment prevalence among subjects having natural resistance to each type of NC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Brains from 1,040 autopsied participants of the Honolulu-Asia Study, the Nun Study, and the 90\u200a+\u200aStudy were examined for NC of AD, Lewy body dementia, microvascular brain injury, hippocampal sclerosis, and limbic predominate TDP-43 encephalopathy. Associations with impairment were assessed for each NC and for NC polymorbidity (variable combinations of 2-5 concurrent NC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Among 387 autopsied decedents with severe cognitive impairment, 20.4% had only AD lesions (ADNC), 25.3% had ADNC plus 1 other NC, 11.1% had ADNC plus 2 or more other NC, 28.7% had no ADNC but 1-4 other NC, and 14.5% had no\/negligible NC. Combinations of any two, three, or four NC were highly frequent among the impaired. Natural resistance to ADNC or any other single NC had a modest impact on overall cohort impairment levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Polymorbidity involving 1-5 types of concurrent NC is a dominant neuropathologic feature of AD and related dementias. This represents a daunting challenge to future prevention and could explain failures of prior preventive intervention trials and of efforts to identify risk factors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-230331","type":"journal-article","created":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T12:17:08Z","timestamp":1690287428000},"page":"307-316","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Neuropathologic Changes of Alzheimer\u2019s Disease and Related Dementias: Relevance to Future Prevention"],"prefix":"10.1177","volume":"95","author":[{"given":"Lon R.","family":"White","sequence":"first","affiliation":[{"name":"Pacific Health Research and Education Institute, Honolulu, HI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria M.","family":"Corrada","sequence":"additional","affiliation":[{"name":"Department of Neurology, UC Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia H.","family":"Kawas","sequence":"additional","affiliation":[{"name":"Department of Neurology, UC Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenna A.","family":"Cholerton","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University, Palo Alto, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve E.","family":"Edland","sequence":"additional","affiliation":[{"name":"School of Public Health and Human Longevity Science, University of California at San Diego, School of Public Health, La Jolla, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret E.","family":"Flanagan","sequence":"additional","affiliation":[{"name":"University of Texas Health San Antonio, Biggs Institute for Alzheimer\u2019s and Neurodegenerative Diseases and Department of Pathology, San Antonio, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Montine","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University, Palo Alto, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,7,24]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.34.7.939"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410340410"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.1007\/BF00293396"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2002.tb04794.x"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.2174\/156720512801322555"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0910-3"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.10.007"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.66"},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-130281"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.04.006"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2017.01.017"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002267"},{"key":"ref013","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25123"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-180162"},{"key":"ref015","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0000000000000265"},{"key":"ref016","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25246"},{"key":"ref017","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz099"},{"key":"ref018","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab092"},{"key":"ref019","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcac052"},{"key":"ref020","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001831"},{"key":"ref021","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002480"},{"key":"ref022","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25380"},{"key":"ref023","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa438"},{"key":"ref024","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab099"},{"key":"ref025","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200832"},{"key":"ref026","doi-asserted-by":"publisher","DOI":"10.2174\/156720512801322618"},{"key":"ref027","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlx030"},{"key":"ref028","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.147389"},{"key":"ref029","doi-asserted-by":"publisher","DOI":"10.1017\/S1041610294001602"},{"key":"ref030","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.01.004"},{"key":"ref031","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-019-0479-y"},{"key":"ref032","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.21442"}],"container-title":["Journal 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