{"doi":"10.1002/alz.14239","title":"Self‐ and study partner–reported cognitive decline in older adults without dementia: The role of α‐synuclein and amyloid biomarkers in the Alzheimer's Disease Neuroimaging Initiative","abstract":"INTRODUCTION: Subjective cognitive decline (SCD) may be an early marker of Alzheimer's disease (AD) pathology. Until recently, it was impossible to measure biomarkers specific for α-synuclein pathology; therefore, its association with subjective reports of cognitive decline is unknown. METHODS: Alzheimer's Disease Neuroimaging Initiative participants without dementia (n = 918) were classified as positive or negative for amyloid beta (Aβ+ or Aβ-) and α-synuclein (α-syn+ or α-syn-) biomarkers. Self- and study partner-reported cognitive decline was measured with the Everyday Cognition (ECog) questionnaire. RESULTS: Per self-report, Aβ+/α-syn+ had the greatest cognitive decline. Aβ-/α-syn+ did not differ from Aβ-/α-syn- across ECog scores. Study partner-reported results had a similar pattern, but Aβ+/α-syn- and Aβ+/α-syn+ did not differ across ECog scores. Mild cognitive impairment classification moderated the study partner-reported memory score. DISCUSSION: While α-syn+ alone did not increase subjective reports of cognitive decline, Aβ+/α-syn+ had the most self- and study partner-rated cognitive decline. Therefore, the presence of multiple pathologies was associated with greater SCD. HIGHLIGHTS: Cerebrospinal fluid α-synuclein (α-syn) seed amplification assay was used to determine α-syn positivity. Amyloid beta (Aβ)-/α-syn-, Aβ-/α-syn+, Aβ+/α-syn-, and Aβ+/α-syn+ biomarker groups were created. Aβ+/α-syn+ had greater subjective cognitive decline (SCD) than the other biomarker groups. Aβ-/α-syn+ did not differ from Aβ-/α-syn- across self- or study-partner reported SCD scores. Study partner-reported subjective memory results were largely driven by participants with mild cognitive impairment.","journal":"Alzheimer s & Dementia","year":2024,"id":464432,"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":0.862,"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":316754,"name":"Katherine J. Bangen","orcid":"0000-0002-1363-3179","position":1,"is_corresponding":false},{"id":1091449,"name":"Lindsay J. Rotblatt","orcid":"0000-0002-2854-577X","position":2,"is_corresponding":false},{"id":316752,"name":"Alexandra J. Weigand","orcid":"0000-0002-7931-1383","position":3,"is_corresponding":false},{"id":300910,"name":"Lauren Edwards","orcid":"0000-0002-8434-9669","position":4,"is_corresponding":false},{"id":642769,"name":"Duygu Tosun","orcid":"0000-0001-5174-3910","position":5,"is_corresponding":false},{"id":108599,"name":"Douglas Galasko","orcid":"0000-0001-6195-3241","position":6,"is_corresponding":false},{"id":300139,"name":"for the Alzheimer's Disease Neuroimaging Initiative","orcid":null,"position":7,"is_corresponding":false},{"id":316753,"name":"Kelsey R. Thomas","orcid":"0000-0003-4277-8876","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T02:04:37.468651Z","pmid":"39311775","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":[]}