Obesity-induced cognitive impairment: Underlying mechanisms and therapeutic prospects

Feb 2, 2026Metabolism open

How Obesity May Cause Thinking Problems and Possible Treatments

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Abstract

Obesity is significantly associated with the risk of cognitive impairment, including disorders such as dementia and depression.

Obesity in middle age may lead to cognitive disorders, including aprosexia and hypomnesis.
Chronic inflammation caused by obesity could impair neuroprotection by activating microglia and increasing β-amyloid deposition.
Imbalances in gut bacteria may reduce the production of beneficial short-chain fatty acids, further harming neuroprotection.
Metabolic syndrome is associated with damage to cerebral vascular structures and white matter integrity.
Genetic factors, comorbidities, and ethnic differences may influence the relationship between obesity and cognitive function.
Bariatric surgery has shown potential to enhance executive function and memory, while lifestyle changes and medications may help reduce inflammation and metabolic issues.

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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.

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Obesity-induced cognitive impairment: Underlying mechanisms and therapeutic prospects

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