Cognitive dysfunction in non-alcoholic fatty liver disease - current knowledge, mechanisms and perspectives

TY - JOUR

T1 - Cognitive dysfunction in non-alcoholic fatty liver disease - current knowledge, mechanisms and perspectives

AU - Kjærgaard, Kristoffer

AU - Mikkelsen, Anne Catrine Daugaard

AU - Wernberg, Charlotte Wilhelmina

AU - Ladegaard Grønkjær, Lea

AU - Eriksen, Peter Lykke

AU - Damholdt, Malene Flensborg

AU - Mookerjee, Rajeshwar Prosad

AU - Vilstrup, Hendrik V Arenstorff

AU - Lauridsen, Mette Enok Munk

AU - Thomsen, Karen Louise

PY - 2021/2

Y1 - 2021/2

N2 - Non-alcoholic fatty liver disease (NAFLD) has emerged as the hepatic component of the metabolic syndrome and now seemingly affects one-fourth of the world population. Features associated with NAFLD and the metabolic syndrome have frequently been linked to cognitive dysfunction, i.e. systemic inflammation, vascular dysfunction, and sleep apnoea. However, emerging evidence suggests that NAFLD may be a cause of cognitive dysfunction independent of these factors. NAFLD in addition exhibits dysbiosis of the gut microbiota and impaired urea cycle function, fa-vouring systemic ammonia accumulation and further promotes systemic inflammation. Such dis-ruption of the gut–liver–brain axis is essential in the pathogenesis of hepatic encephalopathy, the neuropsychiatric syndrome associated with progressive liver disease. Considering the growing burden of NAFLD, the morbidity from cognitive impairment is expected to have huge societal and economic impact. The present paper provides a review of the available evidence for cognitive dysfunction in NAFLD and outlines its possible mechanisms. Moreover, the clinical challenges of characterizing and diagnosing cognitive dysfunction in NAFLD are discussed.

AB - Non-alcoholic fatty liver disease (NAFLD) has emerged as the hepatic component of the metabolic syndrome and now seemingly affects one-fourth of the world population. Features associated with NAFLD and the metabolic syndrome have frequently been linked to cognitive dysfunction, i.e. systemic inflammation, vascular dysfunction, and sleep apnoea. However, emerging evidence suggests that NAFLD may be a cause of cognitive dysfunction independent of these factors. NAFLD in addition exhibits dysbiosis of the gut microbiota and impaired urea cycle function, fa-vouring systemic ammonia accumulation and further promotes systemic inflammation. Such dis-ruption of the gut–liver–brain axis is essential in the pathogenesis of hepatic encephalopathy, the neuropsychiatric syndrome associated with progressive liver disease. Considering the growing burden of NAFLD, the morbidity from cognitive impairment is expected to have huge societal and economic impact. The present paper provides a review of the available evidence for cognitive dysfunction in NAFLD and outlines its possible mechanisms. Moreover, the clinical challenges of characterizing and diagnosing cognitive dysfunction in NAFLD are discussed.

KW - Ammonia

KW - Cognition

KW - Hepatic encephalopathy

KW - Inflammation

KW - Neurodegeneration

KW - Neuropsychology

KW - Non-alcoholic steatohepatitis

KW - Psychometric

KW - Vascular dysfunction

U2 - 10.3390/jcm10040673

DO - 10.3390/jcm10040673

M3 - Review

C2 - 33572481

SN - 2077-0383

VL - 10

JO - Journal of Clinical Medicine

JF - Journal of Clinical Medicine

IS - 4

M1 - 673

ER -