Obesity's cognitive consequences: leptin's influence on dementia

Abstract

Dementia is characterised by progressive cognitive decline and is increasingly associated with obesity. Obesity is characterised by a number of pathological features, including excess fat accumulation, insulin resistance, gut dysbiosis, oxidative stress, inflammatory activation and systemic inflammation. These pathological factors trigger neuroinflammation and brain damage, highlighting the complex relationship between metabolic health and cognitive function. The amount of leptin in the bloodstream correlates with the amount of body fat and regulates cognitive processes as well as metabolic functions through its effects on the central nervous system. However, obesity can lead to leptin resistance, which may contribute to the development of neurodegenerative disorders such as dementia by impairing leptin's ability to maintain cognitive function. This article discusses the gut-brain axis as a critical mediator of the effects of obesity on cognitive health and highlights the impact of gut dysbiosis on cognitive decline as a result of neuroinflammation. Obesity-specific systemic inflammation exacerbates neurodegeneration, highlighting the need for integrated approaches to treat obesity and its cognitive consequences. Addressing the pathological features of obesity by optimising leptin signalling may offer promising strategies to prevent or slow the progression of cognitive decline associated with obesity and metabolic syndrome.