Benfotiamine and Cognitive Decline in Alzheimer's Disease: Results of a Randomized Placebo-Controlled Phase IIa Clinical Trial. Academic Article uri icon

Overview

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.

authors

  • Gibson, Gary E.
  • Luchsinger, José A
  • Cirio, Rosanna
  • Chen, Huanlian
  • Franchino-Elder, Jessica
  • Hirsch, Joseph A
  • Bettendorff, Lucien
  • Chen, Zhengming
  • Flowers, Sarah A
  • Gerber, Linda M
  • Grandville, Thomas
  • Schupf, Nicole
  • Xu, Hui
  • Stern, Yaakov
  • Habeck, Christian
  • Jordan, Barry
  • Fonzetti, Pasquale

publication date

  • January 1, 2020

Research

keywords

  • Alzheimer Disease
  • Brain
  • Cognitive Dysfunction
  • Thiamine

Identity

PubMed Central ID

  • PMC7880246

Scopus Document Identifier

  • 85097003558

Digital Object Identifier (DOI)

  • 10.3233/JAD-200896

PubMed ID

  • 33074237

Additional Document Info

volume

  • 78

issue

  • 3