{"doi":"10.1002/alz.12922","title":"Initial non‐amnestic symptoms relate to faster rate of functional and cognitive decline compared to amnestic symptoms in neuropathologically confirmed dementias","abstract":"INTRODUCTION: The relationship between initial cognitive symptoms and subsequent rate of clinical decline is important in clinical care and the design of dementia clinical trials. METHODS: This retrospective longitudinal, autopsy-confirmed, cohort study among 2426 participants in the National Alzheimer's Coordinating Center database included Alzheimer's disease (AD) pathology, n = 1187; Lewy body pathology (LBP), n = 331; and mixed pathology (AD-LBP), n = 904. The predominant initial cognitive symptom was assessed clinically. Linear mixed models evaluated the longitudinal outcome of the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score. RESULTS: Non-amnestic initial symptoms had a faster rate of decline than amnestic symptoms in all three groups. Language symptoms had a faster rate of decline in all three groups. Executive symptoms had a faster rate of decline than amnestic in AD and AD-LBP. There was a similar trend for visuospatial symptoms in AD-LBP. DISCUSSION: Initial cognitive symptoms, despite varied underlying pathology, are a predictor of longitudinal functional outcomes among dementias. HIGHLIGHTS: Initial non-amnestic symptoms had a faster rate of longitudinal cognitive and functional decline on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores than amnestic symptoms among Alzheimer's disease, Lewy body pathology, and mixed neuropathology. Given the relative size of CDR-SB changes in Alzheimer's disease clinical trials, clarifying the nature of initial symptoms could be an important variable in ensuring appropriately designed clinical trials.","journal":"Alzheimer s & Dementia","year":2023,"id":358924,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.6464,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":294485,"name":"James Bena","orcid":"0000-0002-7592-0480","position":1,"is_corresponding":false},{"id":1109615,"name":"Emily F Maly","orcid":null,"position":2,"is_corresponding":false},{"id":108604,"name":"James B. Leverenz","orcid":"0000-0002-0896-0749","position":3,"is_corresponding":false},{"id":341325,"name":"Jagan A. Pillai","orcid":"0000-0001-6784-824X","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T01:13:48.379546Z","pmid":"36648159","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":[]}