{"doi":"10.1002/alz.70511","title":"Tau, atrophy, and domain‐specific cognitive impairment in typical Alzheimer's disease","abstract":"INTRODUCTION: A granular understanding of the mechanisms linking tau pathology to cognitive decline in Alzheimer's disease is crucial. We investigate mediating effects of medial temporal lobe (MTL) and neocortical neurodegeneration on tau-induced domain-specific cognitive impairment in amyloid-beta (Aβ) positive cognitively normal and impaired adults. METHODS: F-Flortaucipir positron emission tomography in 319 Aβ-positive individuals. Cognitive functions across six domains were isolated by adjusting for other cognitive measures. RESULTS: MTL tau correlated with memory subdomains, neocortical tau with executive function, and both with semantic fluency. Specific structural measures partially mediated these tau-cognition associations: Brodmann area 35 mediated tau-immediate and tau-delayed recall, posterior hippocampus tau-recognition, and inferior temporal cortex tau-semantic fluency associations. DISCUSSION: Our findings provide a nuanced understanding of region-specific macrostructural atrophy as one pathway of tau-induced cognitive changes, aligning with known tau spread patterns. Additionally, isolating cognitive functions is a promising approach for future research. HIGHLIGHTS: Medial temporal lobe tau was related to memory domains; neocortical tau to executive function. Both tau positron emission tomography measures were associated with semantic fluency. Specific regional atrophy partially mediated tau-induced cognitive changes. Other mechanistic links between tau and cognitive subdomains require investigation. Isolated cognitive domains should be explored as future avenues of research.","journal":"Alzheimer s & Dementia","year":2025,"id":513960,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"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":259728,"name":"Long Xie","orcid":"0000-0002-7184-7028","position":1,"is_corresponding":false},{"id":1227730,"name":"Emily McGrew","orcid":null,"position":2,"is_corresponding":false},{"id":561487,"name":"Alexa Pichet Binette","orcid":"0000-0001-5218-3337","position":3,"is_corresponding":false},{"id":846414,"name":"Nicola Spotorno","orcid":"0000-0001-5404-8788","position":4,"is_corresponding":false},{"id":611130,"name":"Danielle van Westen","orcid":"0000-0001-8649-9874","position":5,"is_corresponding":false},{"id":230942,"name":"Niklas Mattsson","orcid":"0000-0002-8885-7724","position":6,"is_corresponding":false},{"id":259082,"name":"Paul A. Yushkevich","orcid":"0000-0001-8543-4016","position":7,"is_corresponding":false},{"id":265855,"name":"Sandhitsu R. Das","orcid":"0000-0003-0530-2887","position":8,"is_corresponding":false},{"id":230045,"name":"David A. Wolk","orcid":"0000-0002-3554-3481","position":9,"is_corresponding":false},{"id":260099,"name":"Laura E.M. Wisse","orcid":"0000-0001-7504-3943","position":10,"is_corresponding":false},{"id":1324358,"name":"and for the Alzheimer's Disease Neuroimaging Initiative","orcid":null,"position":11,"is_corresponding":false},{"id":1032009,"name":"Anika Wuestefeld","orcid":"0000-0003-1779-3388","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-19T02:48:23.284782Z","pmid":"40709494","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":[]}