Liver disease as a risk factor for cognitive decline and dementia: An Under-recognized issue #

We read with great interest the article by Newton and colleagues1 showing the presence of cognitive deficits in patients diagnosed with primary biliary cirrhosis, with a significant decline detected over a 2-year follow-up. Notably, cognitive impairment was associated with the presence of significant structural brain lesions and abnormality in dynamic blood pressure regulation.1 Although it is well established that advanced forms of liver disease are frequently accompanied by overt and global cognitive deficits (hepatic encephalopathy), the article by Newton et al. adds to the current evidence that the presence of chronic liver disease might represent an important risk factor for neuropsychological impairment. Accordingly, it has been previously demonstrated that patients with chronic hepatitis C virus infection frequently show a decline in power of concentration and speed of working memory,2 and that they perform significantly worse than healthy controls on verbal learning and memory.3 Other evidence suggesting a relation between liver and brain function include the observation that liver-derived circulating insulin-like growth factor-1 affects crucial aspects of mature brain function, and may exert a significant procognitive function in adults.4 Besides this evidence, we believe that another important issue that may merit further investigation in future studies is the potential association between the presence of nonalcoholic fatty liver disease (NAFLD) and the development of cognitive decline in adults. Accordingly, previous studies have shown that patients with NAFLD have an increased risk of carotid atherosclerosis as compared to controls,5 and increased carotid intima media thickness has been in turn associated with cognitive impairment.6 In addition, patients with NAFLD have been reported to have high prevalence rates of metabolic syndrome,7 which is considered a predictor of future cognitive decline.8 Finally, it is noteworthy that recent studies found that elevated gamma glutamyltransferase, a common biochemical finding in NAFLD, may be involved in the pathogenesis of Alzheimer disease by promoting oxidative stress.9 Although the association between NAFLD with cognitive decline certainly merits further investigation, we believe that the evidence presented here underlines the importance to perform a longitudinal evaluation of cognitive function in all patients suffering from chronic liver disease. Yusuf Yilmaz [email protected]*, Osman Ozdogan*, * Department of Gastroenterology, Marmara University, School of Medicine,, Istanbul, Turkey.