The Presence and Severity of NAFLD are Associated With Cognitive Impairment and Hippocampal Damage

Abstract

Context Although cognitive impairment in nonalcoholic fatty liver disease (NAFLD) has received attention in recent years, little is known about detailed cognitive functions in histologically diagnosed individuals. Objective This study aimed to investigate the association of liver pathological changes with cognitive features, and further explore the underlying brain manifestations. Methods and patients We performed a cross-sectional study in 320 subjects who underwent liver biopsy. Among the enrolled participants, 225 individuals underwent assessments of global cognition and cognitive subdomains. Furthermore, 70 individuals received functional magnetic resonance imaging (fMRI) scans for neuroimaging evaluations. The associations among liver histological features, brain alterations and cognitive functions were evaluated using structural equation model. Results Compared with controls, patients with NAFLD had poorer immediate memory and delayed memory. Severe liver steatosis (OR = 2.189, 95% CI: 1.020-4.699) and ballooning (OR = 3.655, 95% CI: 1.419 -9.414) was related to a higher proportion of memory impairment. Structural MRI showed that patients with nonalcoholic steatohepatitis exhibited volume loss in left hippocampus and its subregions of subiculum and presubiculum. Task-based MRI showed that patients with nonalcoholic steatohepatitis had decreased left hippocampal activation. Path analysis demonstrated that higher NAFLD activity scores were associated with lower subiculum volume and reduced hippocampal activation, and such hippocampal damage contributed to lower delayed memory scores. Conclusion We are the first to report the presence and severity of NAFLD to be associated with an increased risk of memory impairment and hippocampal structural and functional abnormalities. These findings stress the significance of early cognitive evaluation in patients with NAFLD.

Alzheimer's disease, a metabolic disorder: Clinical advances and basic model studies (Review)

“…In addition, the aforementioned metabolic diseases also affect the course of AD through some potential mechanisms. The cAMP/PKA signaling pathway, the IRS-Akt pathway, neuronal apoptosis, neuroinflammation and oxidative stress are all factors that have been verified by several research groups; they become common ground between metabolic diseases and cognitive impairment (25)(26)(27)(28)(46)(47)(48)(49)(65)(66)(67). These commonalities lead the present authors to focus on the potential of drugs commonly used to treat metabolic diseases for the treatment of AD.…”

“…A study has demonstrated that increased VAT is associated with decreased grey matter density and cognitive function and that such a relationship is age-dependent ( 48 ). For patients with NAFLD, hepatic fat deposits are significantly associated with smaller overall brain volumes as well as smaller cingulate and hippocampal volumes ( 49 ). Even after weight loss, NAFLD is still associated with smaller total brain volume ( 50 ).…”

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

“…Structural brain changes such as reduced brain and grey-matter volume, hippocampal volume loss, and altered functional and brain connectivity were associated with NAFLD [ 45 , 46 , 47 ]. Additionally, the severity of NAFLD, especially when combined with metabolic conditions like diabetes, was linked to more pronounced cognitive decline, chronic cerebrovascular dysfunction, and hypoperfusion [ 40 ].…”