Microbiota-Gut-Brain Axis Mechanisms in Cognitive Impairment Associated with Central Obesity

Central obesity (CO), characterized by excessive visceral adipose tissue (VAT) accumulation, is increasingly recognized as a risk factor for cognitive decline, dementia, and Alzheimer's disease (AD). This review summarizes current evidence linking CO, particularly VAT accumulation, to cognitive impairment and discusses the microbiota-gut-brain axis as a mechanistic framework for interpreting this association.

Studies published in recent years suggest that VAT-related indices, such as waist circumference, waist-to-hip ratio, and imaging-derived VAT measures, are more closely associated with cognitive dysfunction than body mass index. Recent neuroimaging studies have linked VAT accumulation with brain atrophy, white matter abnormalities, altered functional connectivity, and increased AD-related pathological burden. Emerging multi-omics evidence further indicates that VAT expansion shows an association with gut microbial dysbiosis, altered microbial metabolites, impaired intestinal barrier function, systemic low-grade inflammation, insulin resistance, and neuroendocrine disturbances. These findings support a model in which VAT-related metabolic and inflammatory alterations may influence brain structure and function through microbiota-mediated, immune, endocrine, and barrier-related pathways. Current evidence is consistent with a VAT-centered model in which CO is associated with cognitive impairment through interconnected inflammatory, metabolic, endocrine, and microbiota-mediated mechanisms. The microbiota-gut-brain axis may provide a useful mechanistic framework linking peripheral metabolic dysfunction with AD vulnerability. Future longitudinal cohort studies and mechanistically informed intervention studies are needed to clarify temporal relationships and to determine whether VAT reduction or microbiota-targeted strategies can improve cognitive or neuroimaging outcomes.