{"doi":"10.1038/s41598-020-71305-2","title":"Association of TDP-43 proteinopathy, cerebral amyloid angiopathy, and Lewy bodies with cognitive impairment in individuals with or without Alzheimer’s disease neuropathology","abstract":"Alzheimer's disease patients typically present with multiple co-morbid neuropathologies at autopsy, but the impact of these pathologies on cognitive impairment during life is poorly understood. In this study, we developed cognitive trajectories for patients with common co-pathologies in the presence and absence of Alzheimer's 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's disease neuropathology. Within our study population, 63% of individuals given the 'gold-standard' neuropathological diagnosis of Alzheimer's 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's disease may actually suffer from a mixed dementia, and therapeutics targeting only Alzheimer's disease-related processes may have severely limited efficacy in these co-morbid populations.","journal":"Scientific Reports","year":2020,"id":66479,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":51,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9455,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":289114,"name":"Sumali Bajaj","orcid":"0000-0002-8313-819X","position":1,"is_corresponding":false},{"id":289116,"name":"Kevin McRae‐McKee","orcid":"0000-0001-9476-0462","position":2,"is_corresponding":false},{"id":290438,"name":"Christoforos Hadjichrysanthou","orcid":null,"position":3,"is_corresponding":false},{"id":274626,"name":"Roy M. Anderson","orcid":"0000-0002-9528-3175","position":4,"is_corresponding":false},{"id":300803,"name":"John Collinge","orcid":"0000-0003-2220-7566","position":5,"is_corresponding":false},{"id":352583,"name":"David X. Thomas","orcid":"0000-0001-6828-0182","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T21:14:50.590588Z","pmid":"32883971","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}