Obesity-induced cognitive impairment: Underlying mechanisms and therapeutic prospects

The prevalence of obesity continues to rise worldwide. Obesity is not only a core risk factor for chronic metabolic diseases, but also significantly associated with the risk of cognitive impairment. Obesity in middle age can cause aprosexia, cognitive disorder, dementia, hypomnesis, and increase the risk of execution decline, depression and anxiety. The underlying mechanisms involve multiple pathological pathways such as neuroinflammation, imbalance of gut microbiota-gut-brain axis, metabolic abnormalities, and imbalance of adipokines. Obesity induced chronic inflammation impairs neuroprotection by activating microglia, exacerbating β-amyloid deposition and neurodegeneration. Intestinal flora disorder impairs neuroprotection by reducing the production of short-chain fatty acids. Metabolic syndrome has synergistic damage to cerebral vascular and white matter microstructure. Genetic factors, comorbidities and ethnic differences clearly moderated the association between obesity and cognition. Among the interventions, bariatric surgery can improve executive function and memory, while lifestyle modification and drug intervention have protective effects by reducing inflammation and metabolic disorders. In the future, we need to focus on precise intervention strategies, such as developing multi-dimensional biomarkers, and optimizing obesity assessment indicators to overcome the limitations of existing studies, so as to provide a basis for phased and individualized prevention and treatment.