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In this study, we developed cognitive trajectories for patients with common co-pathologies in the presence and absence of Alzheimer\u2019s disease neuropathology. Cognitive trajectories were modelled in a Bayesian hierarchical regression framework to estimate the effects of each neuropathology on cognitive decline as assessed by the mini-mental state examination and the clinical dementia rating scale sum of boxes scores. We show that both TDP-43 proteinopathy and cerebral amyloid angiopathy associate with cognitive impairment of similar magnitude to that associated with Alzheimer\u2019s disease neuropathology. Within our study population, 63% of individuals given the \u2018gold-standard\u2019 neuropathological diagnosis of Alzheimer\u2019s disease in fact possessed either TDP-43 proteinopathy or cerebral amyloid angiopathy of sufficient severity to independently explain the majority of their cognitive impairment. This suggests that many individuals diagnosed with Alzheimer\u2019s disease may actually suffer from a mixed dementia, and therapeutics targeting only Alzheimer\u2019s disease-related processes may have severely limited efficacy in these co-morbid populations.<\/jats:p>","DOI":"10.1038\/s41598-020-71305-2","type":"journal-article","created":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T06:04:10Z","timestamp":1599113050000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Association of TDP-43 proteinopathy, cerebral amyloid angiopathy, and Lewy bodies with cognitive impairment in individuals with or without Alzheimer\u2019s disease neuropathology"],"prefix":"10.1038","volume":"10","author":[{"given":"David X.","family":"Thomas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumali","family":"Bajaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"McRae-McKee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoforos","family":"Hadjichrysanthou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy M.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Collinge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,3]]},"reference":[{"key":"71305_CR1","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1016\/S1474-4422(11)70156-9","volume":"10","author":"ME Murray","year":"2011","unstructured":"Murray, M. 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