Abstract
Cognitive frailty combines physical frailty with cognitive impairment without dementia, identifying older adults vulnerable to adverse outcomes. Candidate microbiome-related pathways in cognitive frailty include dysfunction of the intestinal epithelial and blood–brain barriers, altered microbial metabolites, systemic and vascular inflammation, anabolic resistance, and neuroinflammation. However, direct evidence is scarce, and most findings derive from physical frailty, sarcopenia, mild cognitive impairment, or Alzheimer’s disease, inviting overinterpretation. This review integrates a multi-database evidence map with a domain-based synthesis of phenotypes, mechanisms, biomarkers, confounding, interventions, and clinical translation. Conducted up to 31 July 2026, the search identified one eligible primary human study directly examining the gut microbiome in cognitive frailty. Its small sample, age and educational imbalances, 16S-based resolution, and lack of external validation preclude clinical biomarker claims despite apparent discrimination. Larger metagenomic frailty studies report lower microbial diversity, gene richness, and butyrate-production capacity, with partial cross-population replication. Dietary, prebiotic, and probiotic trials demonstrate microbiome target engagement and report selected physical or cognitive benefits, but these outcomes are inconsistent, rarely assessed together, and not established as microbiome-mediated; fecal microbiota transplantation remains experimental. The microbiome should be considered a potential component of multidomain risk models rather than a stand-alone biomarker. Translation requires standardized phenotyping, longitudinal multi-omics, causal diagrams, external validation, and trials with concurrent physical and cognitive endpoints.