The Implication of Physiological Ketosis on The Cognitive Brain: A Narrative Review

Optimal cognitive functions are necessary for activities of daily living and self-independence. Cognitive abilities are acquired during early childhood as part of progressive neurodevelopmental milestones; unfortunately, regressive changes can occur as part of physiological aging, or more ominously, pathological diseases, such as Alzheimer's disease (AD). Cases of AD and its milder subset, mild cognitive impairment (MCI), are rising and would impose a burdensome impact beyond the individual level. Various dietary and nutritional approaches have potential for promising results in managing cognitive deterioration. Glucose is the core source of bioenergy in the body; however, glucose brain metabolism could be affected in aging cells or due to disease development. Ketone bodies are an efficient alternate fuel source that could compensate for the deficient glycolytic metabolism upon their supra-physiologic availability in the blood (ketosis), which, in turn, could promote cognitive benefits and tackle disease progression. In this review, we describe the potential of ketogenic approaches to produce cognitive benefits in healthy individuals, as well as those with MCI and AD. Neurophysiological changes of the cognitive brain in response to ketosis through neuroimaging modalities are also described in this review to provide insight into the ketogenic effect on the brain outside the framework of purely molecular explanations.