1. Benfotiamine and Cognitive Decline in Alzheimer's Disease: Results of a Randomized Placebo-Controlled Phase IIa Clinical Trial.
- Author
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Gibson GE, Luchsinger JA, Cirio R, Chen H, Franchino-Elder J, Hirsch JA, Bettendorff L, Chen Z, Flowers SA, Gerber LM, Grandville T, Schupf N, Xu H, Stern Y, Habeck C, Jordan B, and Fonzetti P
- Subjects
- Aged, Aged, 80 and over, Alzheimer Disease diagnostic imaging, Alzheimer Disease genetics, Alzheimer Disease physiopathology, Aniline Compounds, Apolipoprotein E4 genetics, Cognitive Dysfunction diagnostic imaging, Cognitive Dysfunction genetics, Cognitive Dysfunction physiopathology, Disease Progression, Ethylene Glycols, Female, Fluorodeoxyglucose F18, Glycation End Products, Advanced blood, Humans, Male, Positron-Emission Tomography, Radiopharmaceuticals, Thiamine therapeutic use, Treatment Outcome, Alzheimer Disease drug therapy, Brain diagnostic imaging, Cognitive Dysfunction drug therapy, Thiamine analogs & derivatives
- 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.
- Published
- 2020
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