{"doi":"10.1093/braincomms/fcaf158","title":"Onset ages of cerebrovascular disease and amyloid and effects on cognition in risk-enriched cohorts","abstract":"Abstract The temporal relationship between cerebrovascular disease (V), indicated by white matter hyperintensities, and beta-amyloid (A) in Alzheimer’s disease remains unclear, prompting speculation about their potential interdependence. Longitudinal data were employed to estimate onset ages and corresponding disease chronicity for A and V (where disease chronicity is calculated as age at measurement minus estimated age of biomarker abnormality onset). In a large, predominantly cognitively unimpaired dataset (n = 877, ages 43–93 years), a V+ threshold was identified, and Sampled Iterative Local Approximation (SILA) was utilized to illustrate the predictable accumulation trajectory of V post-onset. Investigating the temporal association between A and V onset ages and accumulation trajectories in preclinical years, four operationalizations of time were examined across two initially cognitively unimpaired samples (n = 240 primary sample from Wisconsin Registry for Alzheimer’s Prevention; n = 123 replication sample from Wisconsin Alzheimer’s Disease Research Center): (i) chronological age, (ii) estimated V+ chronicity, (iii) years since baseline scan, and (iv) estimated A+ chronicity. Results indicated that while both diseases are age-related, their onsets and trajectories are independent of each other. In addition, results indicated that V and A accumulation trajectories were highly predictable relative to onset of positivity for each biomarker. Cognitive decline across multiple cognitive domains was fastest when both V and A were present based on last available amyloid PET and MRI scan, with greater A chronicity being a more salient predictor of cognitive decline in these samples.","journal":"Brain Communications","year":2025,"id":540958,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":758398,"name":"Elizabeth M. 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Langhough","orcid":null,"position":17,"is_corresponding":false},{"id":340627,"name":"Lianlian Du","orcid":null,"position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T02:52:42.901627Z","pmid":"40337464","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":[]}