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

doi:10.1016/j.addr.2022.114537

Targeting the liver in dementia and cognitive impairment: Dietary macronutrients and diabetic therapeutics

Adv Drug Deliv Rev. 2022 Nov:190:114537. doi: 10.1016/j.addr.2022.114537. Epub 2022 Sep 14.

Authors

Nicholas J Hunt¹, Devin Wahl², Lara J Westwood³, Glen P Lockwood³, David G Le Couteur⁴, Victoria C Cogger⁵

Affiliations

¹ Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2008, Australia; Charles Perkins Centre, The University of Sydney, Sydney, NSW 2008, Australia; Sydney Nano Institute, The University of Sydney, Sydney, NSW 2008, Australia; ANZAC Research Institute & Centre for Education and Research on Ageing, Concord Repatriation General Hospital, Concord, NSW 2139, Australia.
² Department of Health and Exercise Science & Centre for Healthy Aging, Colorado State University, CO 80523, United States.
³ Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2008, Australia; ANZAC Research Institute & Centre for Education and Research on Ageing, Concord Repatriation General Hospital, Concord, NSW 2139, Australia.
⁴ Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2008, Australia; Charles Perkins Centre, The University of Sydney, Sydney, NSW 2008, Australia; ANZAC Research Institute & Centre for Education and Research on Ageing, Concord Repatriation General Hospital, Concord, NSW 2139, Australia.
⁵ Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2008, Australia; ANZAC Research Institute & Centre for Education and Research on Ageing, Concord Repatriation General Hospital, Concord, NSW 2139, Australia. Electronic address: victoria.cogger@sydney.edu.au.

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.

Keywords: Alzheimer’s disease; Diet; Mitochondrial dysfunction; Neuroinflammation; Oxidative stress; Precision medicine; Prevention.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cognitive Dysfunction* / drug therapy
Dementia* / drug therapy
Diabetes Mellitus, Type 2* / drug therapy
Diet
Glucose
Humans
Insulin
Liver
Nutrients

Substances

Insulin
Glucose

Grants and funding

F32 AG069361/AG/NIA NIH HHS/United States