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Recently, studies have suggested that other neurodegenerative comorbidities such as limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), Lewy body disease (LBD), and cerebrovascular disease frequently co-occur with Alzheimer disease neuropathologic change (ADNC) and may have significant cognitive effects both in isolation and synergistically with ADNC. Herein, we study the relative clinical impact of these multiple neurodegenerative pathologies in 704 subjects. Each of these pathologies is relatively common in the cognitively impaired population, while cerebrovascular pathology and ADNC are the most common in cognitively normal individuals. Moreover, while the number of concurrent neuropathologic entities rises with age and has a progressively deleterious effect on cognition, 44.3% of cognitively intact individuals are resistant to having any neurodegenerative proteinopathy (compared to 15.2% of cognitively impaired individuals) and 83.5% are resistant to having multiple concurrent proteinopathies (compared to 64.6% of cognitively impaired individuals). The presence of at least 1 APOE \u03b54 allele was associated with impaired cognition and the presence of multiple proteinopathies, while APOE \u03b52 was protective against cumulative proteinopathies. These results indicate that maintenance of normal cognition may depend on resistance to the development of multiple concurrent proteinopathies.<\/jats:p>","DOI":"10.1093\/jnen\/nlac115","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T14:57:09Z","timestamp":1669993029000},"page":"110-119","source":"Crossref","is-referenced-by-count":26,"title":["Cognitive resistance to and resilience against multiple comorbid neurodegenerative pathologies and the impact of <i>APOE<\/i> status"],"prefix":"10.1093","volume":"82","author":[{"given":"Jamie M","family":"Walker","sequence":"first","affiliation":[{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai , New York, New York, USA"},{"name":"Department of Neuroscience, Icahn School of Medicine at Mount Sinai , New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy E","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai , New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,12,2]]},"reference":[{"key":"2024032523493343700_nlac115-B1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1002\/ca.980080612","article-title":"An English translation of Alzheimer's 1907 paper, \u201cUber eine eigenartige Erkankung der Hirnrinde\u201d","volume":"8","author":"Alzheimer","year":"1995","journal-title":"Clin Anat"},{"key":"2024032523493343700_nlac115-B2","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41582-019-0244-7","article-title":"Ageing as a risk factor for neurodegenerative disease","volume":"15","author":"Hou","year":"2019","journal-title":"Nat Rev 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