Brain and Mind Research Institute, Weil Cornell Medicine, New York, NY, USA.
Burke Neurological Institute, White Plains, NY, USA.
J Alzheimers Dis. 2020;78(3):989-1010. doi: 10.3233/JAD-200896.
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.
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.
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.
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).
Oral benfotiamine is safe and potentially efficacious in improving cognitive outcomes among persons with MCI and mild AD.
在临床前模型中，苯磷硫胺可有效改善阿尔茨海默病（AD）的临床和生物学病理，包括认知障碍、淀粉样β斑块、神经原纤维缠结、葡萄糖代谢降低、氧化应激、晚期糖基化终产物（AGE）增加和炎症。
在一项安慰剂对照试验中，收集苯磷硫胺治疗遗忘型轻度认知障碍（aMCI）或 AD 轻度痴呆患者的可行性、安全性和疗效的初步数据。
对苯磷硫胺组进行为期 12 个月的治疗，以观察与安慰剂组相比，临床衰退是否会延迟。主要临床结局为阿尔茨海默病评估量表认知分量表（ADAS-Cog）。次要结局为临床痴呆评定量表（CDR）评分和氟脱氧葡萄糖（FDG）摄取，采用脑正电子发射断层扫描（PET）测量。血液 AGE 作为探索性结局进行检查。
参与者接受苯磷硫胺（34 例）或安慰剂（36 例）治疗。苯磷硫胺治疗安全。与安慰剂组相比，苯磷硫胺组 ADAS-Cog 增加幅度低 43%，表明认知衰退程度较低，且该效果接近统计学意义（p = 0.125）。与安慰剂组相比，苯磷硫胺组 CDR 恶化程度低 77%（p = 0.034），且在 APOEɛ4 非携带者中作用更强。苯磷硫胺显著降低 AGE 增加（p = 0.044），且在 APOEɛ4 非携带者中作用更强。探索性分析得出的 FDG PET 模式评分显示，治疗 1 年后存在治疗效果（p = 0.002）。
口服苯磷硫胺治疗 MCI 和轻度 AD 患者安全且可能有效改善认知结局。
