Efficacy and Safety of Adding Kami Guibi‐tang to Acetylcholinesterase Inhibitor for Cognitive Function in Mild Alzheimer’s Disease: A Pilot, Randomized, Double‐blind, Placebo‐controlled Trial

Abstract

AbstractBackgroundThe main treatments for mild AD have been acetylcholinesterase inhibitors(AChEI). However, no current drugs can fundamentally treat AD or reverse advanced cognitive decline. This clinical study was conducted to explore the efficacy and safety of adding Kami Guibi‐tang(KGT) to AChEI for cognitive function in elderly patients with mild AD.MethodThis study was designed as the pilot for a larger randomized, double‐blind, placebo‐controlled study. Elderly participants aged 55 to 90 years diagnosed with mild AD. Subjects were randomized to receive either KGT or placebo for 24 weeks, in addition to their regular AChEI. The primary study outcome was treatment efficacy as assessed by the relative amount of change over the study period in total scores on the Dementia version of the Seoul Neuropsychologic Screening Battery(SNSB‐D). Changes in SNSB sub‐scores such as the Korean Mini‐Mental State Exam(K‐MMSE) and in scores on the Korean version of Quality of Life‐Alzheimer’s Disease(KQoL‐AD), and the Caregiver‐Administered Neuropsychiatric Inventory(CGA‐NPI) were assessed as secondary outcomes. We also monitored patient safety parameters including adverse events and abnormalities in blood tests, electrocardiogram, and brain magnetic resonance imaging tests.Result7 participants in the KGT group and 7 participants in the placebo group completed the 24‐week trial. There were no significant changes in SNSB‐D total/subindex scores, KQoL‐AD or CGA‐NPI scores for either group, and no significant differences were observed between the two groups. K‐MMSE scores were decreased significantly within each group, but were not significantly different between groups. No adverse events related to KGT were reported. In addition, we compared / analyzed the results of a previous pilot study conducted on amnestic mild cognitive impairment(aMCI) with the same protocol as this study. The aMCI group showed a significant improvement in the total SNSB‐D score(especially in the memory domain) and K‐MMSE and Korean Instrumental Activities of Daily Living scores compared with the mild AD group.ConclusionAdding KGT to AChEI did not significantly improve cognitive function in SNSB compared to placebo. Although KGT did not show cognitive improvement in the patients with mild AD in this study, we suggest that KGT would have a positive effect on the patients with early stages of cognitive impairment such as aMCI.