Cognitive Implications of Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) affects around a quarter of the global population and emerges as a hepatic manifestation of the metabolic syndrome. Beyond its hepatic and cardiometabolic sequelae, accumulating evidence implicates NAFLD in a spectrum of cognitive alterations ranging from subtle impairments in attention, memory and processing speed to mood disturbances and increased risk of vascular dementia. The pathophysiology is multifactorial, involving systemic inflammation, insulin resistance and cerebrovascular dysfunction, as well as disruption of the gut–liver–brain axis with resultant neuroinflammation and ammonia accumulation. Neuroimaging studies have demonstrated region-specific changes in cortical thickness and white matter integrity in individuals with hepatic steatosis, while epidemiological cohorts suggest subtype-dependent variation in dementia risk. Together, these findings underscore a bidirectional interplay in which metabolic derangements of the liver contribute to neurocognitive decline, and in turn cognitive impairment may hinder lifestyle interventions. Understanding these connections is of global significance given the rising prevalence of NAFLD and its potential to exacerbate the burden of cognitive disorders. Practical applications include refined risk stratification for cognitive decline in hepatology clinics and exploration of anti-inflammatory, metabolic and microbiome-targeted therapies to preserve brain health in affected individuals.

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Cognitive Implications of Non-Alcoholic Fatty Liver Disease publication trend

The graph below shows the total number of articles in cognitive implications of non-alcoholic fatty liver disease across all publications each year (not limited to Nature Index journals).

Technical terms

Non-alcoholic fatty liver disease (NAFLD): Excessive lipid accumulation in the liver in the absence of significant alcohol intake, forming part of the metabolic syndrome.

Metabolic dysfunction-associated fatty liver disease (MAFLD): A revised nomenclature emphasising the presence of metabolic risk factors in defining fatty liver disease.

Cortical thickness: A neuroimaging measure of the thickness of the cerebral cortex, reflecting neuronal and synaptic integrity.

Gut–liver–brain axis: A bidirectional communication network involving microbial metabolites, immune mediators and neuroactive compounds linking the gut, liver and central nervous system.

Vascular dementia: A form of cognitive decline resulting from cerebrovascular pathology, including small vessel disease and infarcts.

References

1. Regional gray matter changes in steatotic liver disease provide a neurobiological link to depression: A cross-sectional UK Biobank cohort study. Metabolism (2024).
2. Association of MAFLD and MASLD with all-cause and cause-specific dementia: a prospective cohort study. Alzheimer's Research & Therapy (2024).
3. Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease—Current Knowledge, Mechanisms and Perspectives. Journal of Clinical Medicine (2021).