Gary E Gibson1,2, José A Luchsinger3, Rosanna Cirio2, Huanlian Chen2, Jessica Franchino-Elder2, Joseph A Hirsch2,4,5, Lucien Bettendorff6, Zhengming Chen7, Sarah A Flowers8, Linda M Gerber7, Thomas Grandville4, Nicole Schupf9, Hui Xu2, Yaakov Stern10, Christian Habeck11, Barry Jordan12,13, Pasquale Fonzetti14. 1. Brain and Mind Research Institute, Weil Cornell Medicine, New York, NY, USA. 2. Burke Neurological Institute, White Plains, NY, USA. 3. Departments of Medicine and Epidemiology, Columbia University Irving Medical Center, New York, NY, USA. 4. Burke Rehabilitation Hospital, White Plains, NY, USA. 5. Lenox Hill Hospital, New York, NY, USA. 6. Laboratory of Neurophysiology, GIGA-Neurosciences, University of Liege, Belgium. 7. Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA. 8. Department of Neuroscience, Georgetown University, Washington, DC, USA. 9. Mailman School of Public Health, The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA. 10. Departments of Neurology, Psychiatry, GH Sergievsky Center, the Taub Institute for the Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA. 11. Department of Neurology and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA. 12. Rancho Los Amigos National Rehabilitation Center, Downey, CA, USA. 13. Department of Neurology, Keck School of Medicine of USC, Los Angeles, CA, USA. 14. Einstein College of Medicine, Bronx NY; Westmed Medical Group White Plains, NY, USA.
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 aplacebo-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.
RCT Entities:
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.
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