Efficacy and Safety of MT104, A Dietary Supplement Based on Seeds and Heat-Killed Probiotics, on Cognitive Function in Patients with Mild Cognitive Impairment: A 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Mild cognitive impairment (MCI) represents the symptomatic predementia stage of Alzheimer's disease (AD). To delay the progression of MCI to AD, appropriate interventions capable of modulating the microbiota-gut-brain (MGB) axis are necessary. This study was designed to assess the efficacy and safety of MT104, a dietary supplement comprising seeds and heat-killed probiotics, based on the biological mechanisms regulating the MGB axis in patients with MCI. This was a multicenter, randomized, double-blind, and placebo-controlled study. All patients were randomly allocated in a 1:1 ratio to the MT104 or placebo group. Global cognition was assessed using the Korean-Montreal Cognitive Assessment (K-MoCA) and Korean-Mini Mental State Examination at baseline and after 12 weeks of treatment. The visuospatial function was assessed using the copying performance from the Rey Complex Figure Test (RCFT), and verbal and visual memory functions were evaluated using the Seoul Verbal Learning Test (SVLT) and RCFT. Differences between groups were analyzed using either the -test or the Mann-Whitney U test. Analyses of covariance and ranked analysis of covariance were performed. The mean changes in verbal memory function, as measured by the SVLT delayed recall, showed clinically significant improvement in the MT104 group relative to the placebo group in the intention-to-treat and per-protocol groups. Global cognition, as measured using the K-MoCA, also significantly improved in the per-protocol group. In addition, no significant findings were identified. This study highlighted the potential of dietary therapeutic strategies focused on reducing the risk of progression from MCI to AD.