Nonalcoholic Fatty Liver Disease

Globally, 1 in 4 adults has nonalcoholic fatty liver disease (NAFLD).1 Encompassing a continuum ranging from steatosis to nonalcoholic steatohepatitis (NASH), NAFLD is a leading cause of liver cirrhosis and hepatocellular cancers and exhibits bidirectional associations with components of the metabolic syndrome.1 NAFLD screening can prevent cardiovascular disease and extrahepatic and hepatic malignancies.1 Dementia is another common condition among adults older than 60 years and a primary cause of disability in developed countries and healthcare burden in old age.2 Globally, its prevalence has been estimated at approximately 4.7%, with 60%–80% being caused by Alzheimer disease (AD), characterized by the pathologic brain deposition of Aβ-amyloid and neurofibrillary tangles.2,3 The genetic basis of late-onset AD (LOAD) explains a small fraction of its incidence, and factors such as education, smoking, physical inactivity, depression, midlife obesity, hypertension, and type 2 diabetes may explain half of LOAD's variations.4 Given the lack of cure for both dementia and NAFLD, preventive efforts are key to alleviating their burden, particularly as midlife obesity and related cardiometabolic risk factors contribute to both conditions and are responsive to lifestyle changes. Furthermore, NAFLD may trigger age-related cognitive decline by directly promoting brain structural changes through the liver-brain axis involving several inflammatory (liver fat–activating microglia, which increases brain cytokine expression) and noninflammatory (insulin resistance, oxidative stress, and hemodynamic) pathways.1,5-7