Targeting the liver in dementia and cognitive impairment: Dietary macronutrients and diabetic therapeutics
Nicholas J. Hunt, Devin Wahl, Lara J. Westwood, Glen P. Lockwood, David G. Le Couteur, Victoria C. Cogger
Abstract
Many people living with dementia and cognitive impairment have dysfunctional mitochondrial and insulin-glucose metabolism resembling type 2 diabetes mellitus and old age. Evidence from human trials shows that nutritional interventions and anti-diabetic medicines that target nutrient-sensing pathways overcome these deficits in glucose and energy metabolism and can improve cognition and/or reduce symptoms of dementia. The liver is the main organ that mediates the systemic effects of diets and many diabetic medicines; therefore, it is an intermediate target for such dementia interventions. A challenge is the efficacy of these treatments in older age. Solutions include the targeted hepatic delivery of diabetic medicines using nanotechnologies and titration of macronutrients to optimize hepatic energy metabolism.