Abstract

Reduced brain glucose metabolism is a consistent feature of Alzheimer's disease (AD), and predicts progression from amnestic mild cognitive impairment (aMCI) to AD dementia. Greater decreases in F18fluorodeoxyglucose uptake with positron emission tomography (FDG-PET) correlate with greater cognitive impairment along the continuum from normal cognitive status to aMCI to AD dementia. In spite of the tight linkage of glucose metabolism to brain function and the decline in AD, only a very limited number of studies have tried to understand why glucose utilization is diminished or tried to reverse this AD-related deficit. Thiamine-dependent enzymes are critical components of glucose metabolism and are reduced in brains of AD patients. Increasing thiamine in humans or animals increases glucose utilization, improves brain metabolism and cognition, including memory. The most effective way to increase blood and brain thiamine is with benfotiamine because of superior pharmacokinetics. Our aim is to test the effect of administering benfotiamine on brain glucose metabolism (FDG-PET) and clinical impact as measured by changes in Assessment Scale-Cognitive subscale (ADAS-Cog) over time in patients with aMCI or AD. A randomized, double-blind, placebo-controlled clinical trial with benfotiamine in patients with aMCI or mild AD was initiated. The primary objective is to determine whether increasing thiamine availability with benfotiamine can slow cognitive decline compared to placebo, as measured by a change in the ADAS Cog score over the twelve-month trial. The secondary objective is to test whether benfotiamine will slow the decline in glucose utilization in patients as measured by FDG-PET. Using blocked, stratified randomization, 76 patients will be assigned to the treatment or placebo group. Stratification is based on Mini Mental Status Exam score (>21) to better understand if treatment responses differ according to initial cognitive impairment. Of the 464 patients screened, 45 patients have been enrolled. Patient characteristics will be detailed in the poster. The trial will determine whether benfotiamine provides clinical or underlying biological benefit for aMCI/AD patients and if this correlates with changes in glucose utilization.

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