Ketogenic Approaches for the Treatment of Alzheimer’s Disease

Issue title: Therapeutic Trials in Alzheimer’s Disease: Where Are We Now?

Guest editors: Paula I. Moreira, Jesus Avila, Daniela Galimberti, Miguel A. Pappolla, Germán Plascencia-Villa, Aaron A. Sorensen, Xiongwei Zhu and George Perry

Article type: Review Article

Authors: Gabuzyan, Renata^{; 1} | Lee, Christopher^{; 1} | Nygaard, Haakon B.^{; *}

Affiliations: Division of Neurology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada

Correspondence: [*] Correspondence to: Haakon B. Nygaard, MD, PhD, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada. E-mail: haakon.nygaard@ubc.ca.

Note: [1] These authors contributed equally to this work.

Abstract: Dementia represents one of the largest and most urgent public health problems across the globe. Modeling projections have estimated that delaying the onset of Alzheimer’s disease (AD) by 6 months would reduce the prevalence by 5%, while a delay of 12 months would reduce the prevalence by 10%. One approach to achieving a delay in the onset of AD is to investigate lifestyle interventions that could be widely implemented with a favorable risk-benefit relationship and socioeconomic profile. Amongst such interventions, there is increasing evidence to support the use of ketogenic interventions in AD. Indeed, it is well known that cerebral glucose metabolism is impaired in AD, even at a preclinical stage, and a growing body of literature suggests that these findings may represent a primary pathogenic mechanism leading to neurodegeneration. Ketones are readily taken up by the brain and can serve as an alternative energy source for neurons and glia, hypothetically bypassing the glucose uptake deficit in AD. In this invited review we discuss the preclinical as well as clinical work aiming to increase ketones as a primary intervention in AD, including variations of the ketogenic diet, medium chain triglyceride supplementation, and newer, more experimental approaches.

Keywords: Alzheimer’s disease, clinical trial, ketogenic diet, medium chain triglyceride, mouse model

DOI: 10.3233/JAD-240186

Journal: Journal of Alzheimer's Disease, vol. 101, no. s1, pp. S443-S453, 2024