{"doi":"10.1002/alz.70990","title":"White matter hyperintensity modulates the amyloid‐tau‐cognition association and anti‐amyloid treatment efficacy in asymptomatic older adults","abstract":"INTRODUCTION: White matter hyperintensities (WMH), a key imaging biomarker of small vessel injury, may play a complex role in Alzheimer's disease (AD). We hypothesize that WMH not only directly contributes to cognitive decline but also moderates the relationship among AD pathology, treatment, and cognitive decline. METHODS: A total of 1169 participants with 240-week follow-up in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study were analyzed. Linear regression models examined WMH's contribution to cognitive decline, its interaction with Aβ on p-Tau217 level, and its interaction with anti-amyloid treatment on cognitive decline. RESULTS: Increase in WMH volume independently contributed to cognitive decline (p = 0.0028). Baseline WMH significantly moderated the relationship between Aβ change and p-Tau217 change (p = 0.0035). Specifically, Aβ accumulation correlated with p-Tau217 increase only in participants with low baseline WMH. WMH growth was associated with cognitive decline only in the treatment group (p < 0.0001). DISCUSSION: WMH modulates the interplay of pathologies, emphasizing the need for comprehensive treatment approaches targeting multiple pathways. HIGHLIGHTS: White matter hyperintensity (WMH) independently contributed to cognitive decline. WMH modulated the longitudinal relationship between Aβ and p-Tau217. WMH interacted with anti-amyloid treatment on longitudinal cognitive decline.","journal":"Alzheimer s & Dementia","year":2025,"id":537487,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9153,"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":1423724,"name":"Yiwen Hong","orcid":null,"position":1,"is_corresponding":false},{"id":1423289,"name":"Yizhe Hu","orcid":"0009-0007-6114-4111","position":2,"is_corresponding":false},{"id":1423290,"name":"Qian Xiao","orcid":"0000-0001-8855-6561","position":3,"is_corresponding":false},{"id":1423291,"name":"Shin‐Lei Peng","orcid":"0000-0001-9241-1808","position":4,"is_corresponding":false},{"id":437768,"name":"Dan Wu","orcid":"0000-0002-9303-5821","position":5,"is_corresponding":false},{"id":277015,"name":"Tengfei Guo","orcid":"0000-0003-2982-0865","position":6,"is_corresponding":false},{"id":320064,"name":"Dengrong Jiang","orcid":"0000-0002-3843-1020","position":7,"is_corresponding":false},{"id":320065,"name":"Zixuan Lin","orcid":"0000-0001-9462-7768","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T02:52:12.997494Z","pmid":"41366853","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":[]}