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Obesity affects 13% of the adult population worldwide and this number is only expected to increase. Obesity is known to have a negative impact on cardiovascular and metabolic health, but it also impacts brain structure and function; it is associated with both gray and white matter integrity loss, as well as decreased cognitive function, including the domains of executive function, memory, inhibition, and language. Especially midlife obesity is associated with both cognitive impairment and an increased risk of developing dementia at later age. However, underlying mechanisms are not yet fully revealed. Here, we review recent literature (published between 2010 and March 2021) and discuss the effects of obesity on brain structure and cognition, with a main focus on the contributions of the gut microbiome, white adipose tissue (WAT), inflammation, and cerebrovascular function. Obesity-associated changes in gut microbiota composition may cause increased gut permeability and inflammation, therewith affecting cognitive function. Moreover, excess of WAT in obesity produces pro-inflammatory adipokines, leading to a low grade systemic peripheral inflammation, which is associated with decreased cognition. The blood-brain barrier also shows increased permeability, allowing among others, peripheral pro-inflammatory markers to access the brain, leading to neuroinflammation, especially in the hypothalamus, hippocampus and amygdala. Altogether, the interaction between the gut microbiota, WAT inflammation, and cerebrovascular integrity plays a significant role in the link between obesity and cognition. Future research should focus more on the interplay between gut microbiota, WAT, inflammation and cerebrovascular function to obtain a better understanding about the complex link between obesity and cognitive function in order to develop preventatives and personalized treatments.

Gut Microbiome, Inflammation, and Cerebrovascular Function: Link Between Obesity and Cognition