Effects of probiotics supplementation on dementia and cognitive impairment: A systematic review and meta-analysis of preclinical and clinical studies

Clinical trials were randomized, and several were double-blind, placebo-controlled studies in older adults with Alzheimer's disease (AD) or mild cognitive impairment (MCI), ages 50–100 years. Six clinical randomized controlled trials were identified. Preclinical evidence consisted of controlled animal studies in mice and rats modeling AD, vascular dementia, or aging-related cognitive impairment.

Oral probiotic regimens with Lactobacillus and Bifidobacterium strains, often multi-strain blends. Daily doses typically 2x10^9 to 2x10^10 CFU; treatment durations around 12 weeks (some up to 16 weeks); capsules or oral supplements; some trials combined probiotics with selenium; one preclinical study used Capsosiphon fulvescens glycoproteins with Lactobacillus plantarum Cf-hGP; another preclinical study used Enterococcus faecium with agave inulin.

Clinical trials showed probiotics improved general cognitive function (MMSE, RBANS, TYM) after treatment, with some studies also reporting improvements in memory, attention and language. Preclinical studies showed memory improvements and favorable biochemical changes (increased BDNF, CREB phosphorylation, improved synaptic plasticity, reduced amyloid-related pathology). The meta-analysis of clinical trials found a significant positive effect on general cognitive function, though heterogeneity was high. Probiotics could be a potential therapeutic strategy for dementia and cognitive impairment, but evidence is limited and translation from preclinical to clinical data is needed; more robust, strain-specific randomized trials are required.

Most evidence is from preclinical studies; clinical evidence is limited to a small number of trials with small sample sizes and methodological variability. Heterogeneity in probiotic strains, doses, durations, and cognitive outcome measures; risk of bias concerns in some preclinical studies; results should be interpreted with caution pending more robust, strain-specific RCTs.