Probiotic supplementation on cognitive and other aging-related physiological functions in middle-aged and older adults with mild cognitive impairment (PCAMCI): protocol for a randomized, triple-blinded, placebo-controlled trial.

The trial is designed to enroll 110 middle-aged and older participants with mild cognitive impairment.

• Participants will be aged 55-80 years with a diagnosis of mild cognitive impairment (MCI).
• Participants will be randomized in a 1:1 ratio to either the probiotic or placebo group, yielding approximately 55 participants per group.
• The study is registered under ChiCTR2400084594.

The probiotic intervention consists of three specific bacterial strains administered over 12 months.

• The probiotic group will receive supplementation consisting of Lactiplantibacillus plantarum ST-III, Lacticaseibacillus rhamnosus KF7, and Lacticaseibacillus paracasei BD5115.
• The placebo group will receive maltodextrin.
• The intervention duration is 12 months.

The primary outcome measure is the effect of probiotic supplementation on cognitive function as assessed by the Montreal Cognitive Assessment (Chinese Beijing Version).

• The Montreal Cognitive Assessment (MoCA) Chinese Beijing Version will be used to measure cognitive function.
• This is designated as the primary outcome of the trial.
• The study targets a high-risk population with pre-existing mild cognitive impairment.

The trial includes a broad range of secondary outcomes related to aging-related physiological functions.

• Secondary outcomes include digestive health, sleep health, facial aging, fundus conditions, olfactory and auditory function, body composition, bone density, and muscle function.
• Brain magnetic resonance imaging will be employed to explore potential underlying mechanisms.
• Wearable devices including a continuous glucose monitor and smart band will also be used.
• This multidimensional assessment approach is intended to explore how probiotic supplementation may impact aging-related physiological functions beyond cognition.

The trial employs a triple-blinded design in which all participants, researchers, and analysts remain blinded to group allocation.

• All participants, researchers, and analysts will remain blinded to information regarding group allocation throughout the study.
• The design is described as a 'rigorously designed, registered clinical trial.'
• The triple-blinded, placebo-controlled design is intended to address the limitation that 'well-designed randomized controlled trials remain limited' in the field of probiotics and MCI.

The study is premised on emerging evidence that gut microbiota modulation may influence neurocognitive function through the gut-brain axis.

• Preliminary studies indicate probiotics' potential benefits for mild cognitive impairment.
• The mechanistic framework centers on the gut-brain axis as a pathway through which probiotic supplementation may delay cognitive decline.
• The target population is described as a 'high-risk population' for cognitive decline.
• The study aims to 'explore the potential underlying mechanisms' linking probiotic supplementation to cognitive and physiological outcomes.