{"doi":"10.3233/jad-200896","title":"Benfotiamine and Cognitive Decline in Alzheimer’s Disease: Results of a Randomized Placebo-Controlled Phase IIa Clinical Trial","abstract":"BACKGROUND: In preclinical models, benfotiamine efficiently ameliorates the clinical and biological pathologies that define Alzheimer's disease (AD) including impaired cognition, amyloid-β plaques, neurofibrillary tangles, diminished glucose metabolism, oxidative stress, increased advanced glycation end products (AGE), and inflammation. OBJECTIVE: To collect preliminary data on feasibility, safety, and efficacy in individuals with amnestic mild cognitive impairment (aMCI) or mild dementia due to AD in a placebo-controlled trial of benfotiamine. METHODS: A twelve-month treatment with benfotiamine tested whether clinical decline would be delayed in the benfotiamine group compared to the placebo group. The primary clinical outcome was the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Secondary outcomes were the clinical dementia rating (CDR) score and fluorodeoxyglucose (FDG) uptake, measured with brain positron emission tomography (PET). Blood AGE were examined as an exploratory outcome. RESULTS: Participants were treated with benfotiamine (34) or placebo (36). Benfotiamine treatment was safe. The increase in ADAS-Cog was 43% lower in the benfotiamine group than in the placebo group, indicating less cognitive decline, and this effect was nearly statistically significant (p = 0.125). Worsening in CDR was 77% lower (p = 0.034) in the benfotiamine group compared to the placebo group, and this effect was stronger in the APOEɛ4 non-carriers. Benfotiamine significantly reduced increases in AGE (p = 0.044), and this effect was stronger in the APOEɛ4 non-carriers. Exploratory analysis derivation of an FDG PET pattern score showed a treatment effect at one year (p = 0.002). CONCLUSION: Oral benfotiamine is safe and potentially efficacious in improving cognitive outcomes among persons with MCI and mild AD.","journal":"Journal of Alzheimer s Disease","year":2020,"id":54489,"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":103,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9422,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":280498,"name":"José A. Luchsinger","orcid":"0000-0002-5886-3648","position":1,"is_corresponding":false},{"id":283202,"name":"Rosanna Cirio","orcid":null,"position":2,"is_corresponding":false},{"id":283203,"name":"Huan‐Lian Chen","orcid":null,"position":3,"is_corresponding":false},{"id":283204,"name":"Jessica Franchino‐Elder","orcid":null,"position":4,"is_corresponding":false},{"id":283205,"name":"Joseph A. Hirsch","orcid":null,"position":5,"is_corresponding":false},{"id":280499,"name":"Lucien Bettendorff","orcid":"0000-0002-2826-6789","position":6,"is_corresponding":false},{"id":280500,"name":"Zhengming Chen","orcid":"0000-0001-9437-6452","position":7,"is_corresponding":false},{"id":257920,"name":"Sarah A. Flowers","orcid":"0000-0002-3513-2260","position":8,"is_corresponding":false},{"id":280501,"name":"Linda M. Gerber","orcid":"0000-0003-0081-3338","position":9,"is_corresponding":false},{"id":283206,"name":"Thomas Grandville","orcid":null,"position":10,"is_corresponding":false},{"id":266059,"name":"Nicole Schupf","orcid":"0000-0001-7560-7657","position":11,"is_corresponding":false},{"id":27361,"name":"Hui Xu","orcid":"0000-0002-3933-4935","position":12,"is_corresponding":false},{"id":55009,"name":"Yaakov Stern","orcid":"0000-0001-7542-3241","position":13,"is_corresponding":false},{"id":280502,"name":"Christian Habeck","orcid":"0000-0001-9961-7446","position":14,"is_corresponding":false},{"id":280503,"name":"Barry D. Jordan","orcid":"0000-0002-5613-8143","position":15,"is_corresponding":false},{"id":283207,"name":"Pasquale Fonzetti","orcid":null,"position":16,"is_corresponding":false},{"id":280497,"name":"Gary E. Gibson","orcid":"0000-0003-2549-2876","position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-07-18T21:04:14.743014Z","pmid":"33074237","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":[]}