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However, little is known about the relationship between LBs and LATE-NC and their combined roles in cognitive impairment and Alzheimer\u2019s dementia in community-dwelling participants. The study included 1670 community-based participants (mean age-at-death, 89.5\u00a0years (SD\u2009=\u20096.65); 69% females) who underwent annual assessments of cognition to create summary measures of global cognition and cognitive domains and evaluation for Alzheimer\u2019s dementia. Systematic neuropathologic evaluations were performed to assess LBs, LATE-NC, and Alzheimer\u2019s disease (AD) pathology. We excluded cases with pathologically confirmed frontotemporal lobar degeneration in this study. Logistic and linear regression analyses were used, adjusted for demographics and AD pathology. LBs were present in 428 (25.6%) decedents (29 nigra-predominant, 165 limbic-type, and 234 neocortical-type) while 865 (51.7%) decedents exhibited LATE-NC (307 stage 1, 167 stage 2, and 391 stage 3). LBs combined with LATE-NC were common (15% of all participants) and in those with Alzheimer\u2019s dementia (25%). Neocortical-type, but not nigral-predominant or limbic-type LBs increased the odds of stage 2\/3 LATE-NC (odds ratio\u2009=\u20091.70; 95% confidence interval\u2009=\u20091.26\u20132.30). The association between neocortical-type LBs and stage 2\/3 LATE-NC was stronger in those under 90\u00a0years of age and in women. In analyses of cognition and Alzheimer\u2019s dementia, LATE-NC and neocortical-type LBs, separately, were related to lower global cognition, five specific cognitive domains, and an increased odds of Alzheimer\u2019s dementia, above and beyond the AD pathology. Limbic-type LBs were related to lower global cognition, and the domains of episodic, working, and semantic memory, and increased odds of Alzheimer\u2019s dementia. Furthermore, there was no interaction between limbic\/neocortical-type LBs and LATE-NC on cognitive function, cognitive domains, or Alzheimer\u2019s dementia. These findings suggest that neocortical-type LBs are associated with LATE-NC, specifically in the younger old and in women. Limbic\/neocortical-type LBs and LATE-NC have separate and additive effects on cognitive function and odds of Alzheimer\u2019s dementia.<\/jats:p>","DOI":"10.1186\/s40478-021-01260-0","type":"journal-article","created":{"date-parts":[[2021,9,25]],"date-time":"2021-09-25T20:02:32Z","timestamp":1632600152000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"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"],"prefix":"10.1186","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2375-8888","authenticated-orcid":false,"given":"Sonal","family":"Agrawal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukriti","family":"Nag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Arfanakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa L.","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,25]]},"reference":[{"key":"1260_CR1","unstructured":"Consensus recommendations for the postmortem diagnosis of Alzheimer's disease (1997) The National Institute on Aging, and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer's Disease. 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