{"doi":"10.1002/alz.12762","title":"Mid‐ and later‐life risk factors for predicting neuropathological brain changes associated with Alzheimer's and vascular dementia: The Honolulu Asia Aging Study and the Age, Gene/Environment Susceptibility‐Reykjavik Study","abstract":"INTRODUCTION: Dementia prediction models are necessary to inform the development of dementia risk reduction strategies. Here, we examine the utility of neuropathological-based risk scores to predict clinical dementia. METHODS: Models were developed for predicting Alzheimer's disease (AD) and non-AD neuropathologies using the Honolulu Asia Aging neuropathological sub-study (HAAS; n = 852). Model accuracy for predicting clinical dementia, over 30 years, was tested in the non-autopsied HAAS sample (n = 2960) and the Age, Gene/Environment Susceptibility-Reykjavik Study (n = 4614). RESULTS: Different models were identified for predicting neurodegenerative and vascular neuropathology (c-statistic range: 0.62 to 0.72). These typically included age, APOE, and a blood pressure-related measure. The neurofibrillary tangle and micro-vascular lesion models showed good accuracy for predicting clinical vascular dementia. DISCUSSION: There may be shared risk factors across dementia-related lesions, suggesting common pathways. Strategies targeting these models may reduce risk or postpone clinical symptoms of dementia as well as reduce neuropathological burden associated with AD and vascular lesions.","journal":"Alzheimer s & Dementia","year":2022,"id":285501,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9563,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":964525,"name":"Denise M. Gaughan","orcid":null,"position":1,"is_corresponding":false},{"id":637991,"name":"Steven D. Edland","orcid":"0000-0002-1153-7335","position":2,"is_corresponding":false},{"id":964526,"name":"Villi Gudnason","orcid":null,"position":3,"is_corresponding":false},{"id":17636,"name":"Lenore J. Launer","orcid":"0000-0002-3238-7612","position":4,"is_corresponding":false},{"id":321296,"name":"Lon R. White","orcid":"0000-0002-5536-3867","position":5,"is_corresponding":false},{"id":251472,"name":"Blossom C. M. Stephan","orcid":"0000-0002-1235-360X","position":0,"is_corresponding":true}],"reference_count":23,"raw_metadata":null,"created_at":"2026-07-19T00:29:44.944555Z","pmid":"36193864","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":[]}