The Metabolic Impact of Nonalcoholic Fatty Liver Disease on Cognitive Dysfunction: A Comprehensive Clinical and Pathophysiological Review

Abstract

Nonalcoholic fatty liver disease (NAFLD) exponentially affects the global healthcare burden, and it is currently gaining increasing interest in relation to its potential impact on central nervous system (CNS) diseases, especially concerning cognitive deterioration and dementias. Overall, scientific research nowadays extends to different levels, exploring NAFLD’s putative proinflammatory mechanism of such dysmetabolic conditions, spreading out from the liver to a multisystemic involvement. The aim of this review is to analyze the most recent scientific literature on cognitive involvement in NAFLD, as well as understand its underlying potential background processes, i.e., neuroinflammation, the role of microbiota in the brain–liver–gut axis, hyperammonemia neurotoxicity, insulin resistance, free fatty acids, and vitamins.

Basic, Translational, and Clinical Research on Dementia

“…The latter molecules can directly affect brain activity, primarily by altering bloodbrain barrier (BBB) integrity, thus allowing their sustained transit, leading to impaired cognition or dementia. This is the view discussed by Giuffrè et al [16], also supporting gut dysbiosis as a crucial role by altering the gut barrier and its interplay with the liver, allowing the entrance of bacterial products that can promote systemic inflammation. Moreover, several factors, including dietary vitamin deficiencies, can promote Aβ-plaques deposition, thus worsening AD outcomes [17].…”