Effects of obesity on brain health and cognition.

Obesity is a global health issue, and cognitive impairment and elevated risk of dementia are emerging as important consequences. Clinical studies have documented that obesity over the life course is associated with cognitive decline, with midlife obesity carrying a particularly high risk. Evidence from both preclinical and clinical studies suggests that obesity has multiple pathophysiological effects on the brain, including hypothalamic dysregulation and disruptions in biological processes that affect the hippocampus and prefrontal cortex, such as metabolic, inflammatory and vascular dysfunction. In this Review, we summarize the global epidemiology of obesity and examine its clinical relevance as a risk factor for cognitive impairment and dementia. We also discuss the peripheral and central mechanisms through which obesity affects brain function and review obesity-related interventions that have been shown to improve cognition. We conclude by identifying crucial gaps in the existing clinical, translational and intervention-focused literature that warrant future investigation.