Changes in Brain Metabolism Induced by Metabolic Challenges and Their Beneficial Roles for Brain Aging

Abstract

Life expectancy has been increasing globally along with the risk of developing Alzheimer’s or other dementias. Diets high in saturated fats, refined sugars and a sedentary lifestyle are determining factors in the development of a metabolic syndrome. These factors induce energy imbalance and dysfunctional brain metabolism, hence increasing the risk of cognitive impairment and/or dementia. A cohort study with mild cognitive impairment found that it was found that the presence of three or more components of a metabolic syndrome increased the risk of Alzheimer’s. On the other hand, hyperglycemia induces glutamate excitotoxicity in neurons, β-amyloid accumulation, tau phosphorylation and oxidative stress. The present chapter will cover the dysregulation of brain metabolism during physiological and pathological aging, and how metabolic challenges such fasting, caloric restriction and ketogenic diet reverts many of the deleterious effects of brain aging, favoring energy balance and cognitive function.