Ketogenic diet therapy in Alzheimer's disease: an updated review

Ketogenic diets (KD) are validated treatments of pharmacoresistant epilepsy. Their interest in neurodegenerative diseases such as Alzheimer's disease (AD) has been suggested, because ketone bodies may reduce neuroinflammation, improve neurotransmitters transport pathway, synaptic maintenance, and reduce brain β-amyloid deposition. In this updated review, we aimed at critically examining the evidence of the past 2 years regarding KD or ketogenic supplements (KS) on cognitive and biological/neuropathological outcomes. We conducted our search in preclinical studies (animal models of AD) or in humans with or without cognitive impairment.Overall, 12 studies were included: four in animal models of AD and eight in humans. In preclinical studies, we found additional evidence for a decrease in cerebral inflammation as well as in specific features of AD: β-amyloid, aggregates of tau protein under KD/KS. Several AD mouse models experienced clinical improvements. Human studies reported significant cognitive benefits, improved brain metabolism and biomarkers change under KD/KS, despite rather short-term interventions. Adherence to KD or KS was acceptable with frequent, but minor gastrointestinal adverse effects.The present review gathered additional evidence for both pathophysiological and clinical benefits of KS/KD in AD. Further studies are warranted with a biomarker-based selection of AD participants and long-term follow-up.