Ectopic fat is defined as the accumulation of fat tissue surrounding, or inside of, a specific organ or compartment. The liver produces the most ectopic fat. Other organs such as skeletal muscle, kidney, heart, and pancreas accumulate fat but to a relatively lesser degree (Kozawa and Shimomura, 2021, Chartrand et al., 2022, Mende and Einhorn, 2022). Abdominal fat distribution, composed of subcutaneous and visceral fat, now be considered a marker of ectopic fat (Wendler G et al.,2022), fat present around abdominal viscera in mesentery and omentum, known as visceral fat, is different from that present in subcutaneous areas (subcutaneous fat)(Ibrahim MM, 2010), and subcutaneous adipose tissue is the largest and least metabolically harmful storage site of excess fat (Smith U , 2015).

Fat accumulation in various organs is thought to be involved in the pathophysiology of insulin resistance (Hong et al., 2016, Chartrand et al., 2022), diabetes mellitus (Gaborit and Dutour, 2016), cardiovascular disease (Cirillo et al., 2021), kidney disease (Mende and Einhorn, 2022), and other clinical entities.

Cognition is the process by which the brain receives and processes external information (Ni Xiushi et al., 2022). This encompasses faculties such as memory, attention, execution, language, and visuospatial aspects. The impairment of one or more of these cognitive faculties is referred to as cognitive dysfunction(Chinese Society of Cardiology et al.,2023).

Obesity, which is highly associated with ectopic fat deposition, has been identified as a risk factor for cognitive impairment and dementia (Bowman et al., 2019, Morys et al., 2021). Obesity has been linked to lower cognitive performance, such as memory (Kharabian Masouleh et al., 2016), as well as an increased risk of Alzheimer's disease (Singh-Manoux et al., 2018). Obesity has been shown to impair executive function, memory, processing speed, and attention in older people with previously apparent normal cognitive function (Dye et al., 2017). Visceral fat area (VFA) measurement is an important indicator of cognitive decline in obese people. For instance, individuals with excessive visceral obesity (VFA> 100 cm2) are more likely to have significantly lower cognitive scores in comparison to non-obese individuals (Moh et al., 2020). Although some studies demonstrate a positive association between high VFA and risk of Mild Cognitive Impairment (MCI) (Yoon et al., 2012, Papachristou et al., 2015), other studies did not find this association (Spauwen et al., 2017), nor an association between ectopic fat and cognitive dysfunction (Parker et al., 2018).

Nonalcoholic fatty liver disease (NAFLD), characterized by ectopic fat accumulation in the liver, referred to as (hepatic steatosis) (Sharma and John, 2022) is a highly prevalent disease with an estimated US prevalence of 35% and a global prevalence of 30% (Clark et al., 2023). A systematic review of observational studies found that NAFLD patients may be at approximately four times higher risk of developing cognitive impairment, and also have lower performance across several cognitive domains, particularly visuospatial and executive function (George et al., 2022). Moreover, tissue volume reduction involving both white and gray matter was also noted in NAFLD patients (Filipovic et al., 2018). However, several studies did not find a correlation between NAFLD and cognitive impairment (Weinstein et al., 2019, Labenz et al., 2021, Shang et al., 2021, Jeong et al., 2022).

Several studies have been published looking at the association between ectopic fat and cognitive dysfunction and changes on brain size and/or structure with conflicting results. To further shed light to this issue we have performed a meta-analysis, aimed to investigate the effects of ectopic fat on brain structure and cognitive function.