{"doi":"10.1101/2024.12.04.626911","title":"Top-down attention and Alzheimer's pathology impact cortical selectivity during learning, influencing episodic memory in older adults","abstract":"Human aging affects the ability to remember new experiences, in part, because of altered neural function during memory formation. One potential contributor to age-related memory decline is diminished neural selectivity -- i.e., a decline in the differential response of cortical regions to preferred vs. non-preferred stimuli during event perception -- yet the factors driving variability in neural selectivity with age remain unclear. We examined the impact of top-down attention and preclinical Alzheimer's disease (AD) pathology on neural selectivity during memory encoding in 156 cognitively unimpaired older participants who underwent fMRI while performing a word-face and word-scene associative memory task. Neural selectivity in face- and place-selective cortical regions was greater during events that were later remembered compared to forgotten. Critically, neural selectivity during learning positively scaled with memory-related variability in top-down attention, whereas selectivity negatively related to early AD pathology, evidenced by elevated plasma pTau181. Path analysis revealed that neural selectivity at encoding mediated the effects of age, top-down attention, and pTau181 on associative memory. Collectively, these data reveal multiple pathways that contribute to memory differences among older adults -- AD-independent reductions in top-down attention and AD-related pathology alter the precision of cortical representations of events during experience, with consequences for remembering.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":489370,"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":0.9514,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":344308,"name":"Alexandra N. Trelle","orcid":"0000-0003-2837-8753","position":1,"is_corresponding":false},{"id":1210801,"name":"America Romero","orcid":null,"position":2,"is_corresponding":false},{"id":573599,"name":"Jennifer Park","orcid":"0000-0001-9602-475X","position":3,"is_corresponding":false},{"id":674194,"name":"Tammy Tran","orcid":"0000-0001-7728-9621","position":4,"is_corresponding":false},{"id":1023385,"name":"Sharon Sha","orcid":null,"position":5,"is_corresponding":false},{"id":246389,"name":"Katrin I. Andreasson","orcid":"0000-0001-8391-4155","position":6,"is_corresponding":false},{"id":279144,"name":"Edward N. Wilson","orcid":"0000-0003-0640-5247","position":7,"is_corresponding":false},{"id":29931,"name":"Elizabeth C. Mormino","orcid":"0000-0002-4542-6537","position":8,"is_corresponding":false},{"id":60737,"name":"Anthony D. Wagner","orcid":"0000-0003-0624-4543","position":9,"is_corresponding":false},{"id":708815,"name":"Jintao Sheng","orcid":"0000-0002-8626-5741","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:08:23.929823Z","pmid":"39713293","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":[]}