The Link Between Metabolic Syndrome and the Brain

Background: Metabolic syndrome (MetS) is a cluster of cardiometabolic conditions that has been linked to high risk for cardiovascular disease, liver complications and several malignancies. More recently MetS has been associated with cognitive dysfunction. Summary: Studies have shown an association with minimal cognitive impairment (MCI), progression to vascular dementia (VaD) and even Alzheimer’s disease (AD). MetS components have been individually explored and glucose intolerance has the strongest association with impairment in several cognitive domains. Several hypotheses have been proposed regarding the pathophysiology underlying the MetS-cognitive dysfunction association and even though insulin resistance plays a major role, more studies are needed to elucidate this topic. Moreover, several other factors contributing to this association have been identified. Liver disease and more specifically Metabolic dysfunction Associated Liver Disease (MASLD) can on its own contribute to cognitive decline through systemic inflammation and higher ammonia levels. Gut dysbiosis that has also been identified in MetS can also lead to cognitive impairment through several mechanisms that result in neurotoxicity. Finally, there are several other factors that may modify the MetS-cognitive dysfunction relationship, such as lifestyle, diet, education status and age. More recently circadian syndrome (CircS) was explored and was found to be even more strongly associated with cognitive impairment. Key message: MetS is associated with cognitive decline. Certain cardiometabolic risk factors have a stronger association with cognitive impairment and there are several factors that may modify this relationship. The aim of this review is to assess and summarize the existing body of evidence on the association between MetS and cognitive impairment and identify areas that necessitate further investigation.