[en] Background. In preclinical models, benfotiamine efficiently ameliorates the clinical and biological pathologies that define Alzheimer’s disease (AD) including impaired cognition, beta amyloid 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 AD-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 APOE ε4 non-carriers. Benfotiamine significantly reduced increases in AGE (p=0.044), and this effect was stronger in the APOE ε4 non-carriers. Exploratory analysis derivation of an FDGPET pattern score showed a treatment effect at one year (p=0.002).
Conclusions Oral benfotiamine is safe and potentially efficacious in improving cognitive outcomes among persons with MCI and mild AD.
Research center :
Brain and Mind Research Institute Giga-Neurosciences - ULiège
Disciplines :
Neurology
Author, co-author :
Gibson, Gary E.
Luchsinger, José A.
Cirio, Rosanna
Chen, Huanlian
Franchino-Elder, Jessica
Hirsch, Joseph A.
Bettendorff, Lucien ; Université de Liège - ULiège > Neurosciences-Neurophysiology
Benfotiamine and cognitive decline in Alzheimer’s disease: Results of a randomized placebo-controlled phase IIa clinical trial.
Publication date :
2020
Journal title :
Journal of Alzheimer's Disease
ISSN :
1387-2877
eISSN :
1875-8908
Publisher :
IOS Press, Netherlands
Volume :
78
Pages :
989-1010
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] ADDF - Alzheimer's Drug Discovery Foundation [US-NY] Burke Rehabilitation Hospital BNI - Burke Neurological Institute
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