Pathophysiological Links Between Obesity and Dementia

Abstract

Obesity is a major global health concern, with prevalence rates rapidly rising due to increased availability of highly processed foods rich in fats and/or sugars and technological advances promoting more sedentary behaviour. There is increasing evidence to suggest that obesity predisposes individuals to developing cognitive impairment and dementia. However, the relationship between the brain and the peripheral metabolic state is complex, and many of the underlying mechanisms of cognitive impairment in obesity are yet to be fully elucidated. To better understand the links between obesity and dementia, further work is required to determine pathological changes occurring in the brain during obesity. In this mini-review, we discuss the role of two pathological features of obesity (the gut-brain axis and systemic inflammation) and their potential contribution to dementia.

Keywords: Cognitive function; Dementia; Gut-brain axis; Inflammation; Obesity.

Fig. 1

Obesity and the potential pathways to dementia. The complex interplay between obesity, neuroinflammation and dementia. Unhealthy lifestyle factors contribute to excess visceral adipose accumulation in obesity, which promotes systemic inflammation and insulin resistance. Obesity is also associated with gut dysbiosis and reduced short chain fatty acid (SCFA) metabolites. These pathological features promote neuroinflammation which in turn promotes the pathological features of dementia (i.e. decreased neurogenesis, synaptic plasticity and long-term potentiation; the development of white matter lesions; neurodegeneration and cerebral atrophy). Ultimately, this may impair cognition and cause dementia. Created with Biorender.com