Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease—Current Knowledge, Mechanisms and Perspectives

Kjærgaard, Kristoffer; Mikkelsen, Anne Catrine Daugaard; Wernberg, Charlotte; Grønkjær, Lea Ladegaard; Eriksen, Peter Lykke; Damholdt, Malene Flensborg; Mookerjee, R.; Vilstrup, Hendrik; Lauridsen, Mette Munk; Thomsen, Karen Louise

doi:10.3390/jcm10040673

Cited by 59 publications

(58 citation statements)

References 158 publications

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“…However, in a study that compared cognitive performance in 874 NAFLD and healthy controls, the NAFLD group performed less well in activities requiring memory and attention (Seo et al, 2016). A deterioration in the cognitive performance of NAFLD subjects was also found in other smaller cross-sectional studies (Kjaergaard et al, 2021). Nevertheless, another report from the NHANES did not show specific cognitive impairment in NAFLD, and nor did other studies (Weinstein et al, 2018).…”

Section: Introductionmentioning

confidence: 89%

Liver Health and Dementia in an Italian Older Population: Findings From the Salus in Apulia Study

Lampignano

Donghia

Griseta

et al. 2021

Front. Aging Neurosci.

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Objectives: Non-alcoholic fatty liver disease (NAFLD) currently affects a quarter of the global population. Systemic inflammation, metabolic syndrome, and coronary artery disease, all conditions associated with NAFLD, have also been related to cognitive dysfunction in older age. The present study aimed to investigate the relationship between NAFLD risk and a dementia diagnosis in a large population-based sample aged > 65 years.Methods: We selected 1,542 participants (723 men) from the Salus in Apulia Study. To assess the risk of fat distribution in the liver, we used the Fatty Liver Index (FLI). Dementia was diagnosed according to the American Psychiatric Association criteria (DSM-5).Results: The overall prevalence of dementia was 8.5% [95% confidence interval (CI): 7–10%]. Subjects with dementia were older [effect size (ES): −0.89, 95% CI: −1.07 to −0.70], had a lower level of education (ES:0.88, 95% CI:0.69–1.06), higher levels of gamma-glutamyl transferase (ES: −0.21, 95% CI: −0.39 to −0.03), lower levels of total cholesterol (ES: −0.24, 95% CI: −0.42 to −0.06) and low-density lipoprotein cholesterol (ES: −0.20, 95% CI: −0.38 to 0.02), and a higher FLI (ES: −0.22, 95% CI: −0.39 to −0.04). In the logistic regression model adjusted for age, sex, education, hypertension, diabetes mellitus, alcohol consumption, smoking habits, stroke, cholesterol, and Apo-E, a dementia diagnosis was positively associated with FLI > 60 [odds ratio (OR):1.81; standard error (SE): 0.53; 95% CI: 1.02–3.21].Conclusion: Our findings suggested that an increased NAFLD risk may be associated to dementia and cognitive decline in older age. Considering the high NAFLD prevalence, the possible adverse disease effects on cognitive performance pose a health problem with significant social and economic implications.

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Section: Introductionmentioning

confidence: 89%

Liver Health and Dementia in an Italian Older Population: Findings From the Salus in Apulia Study

Lampignano

Donghia

Griseta

et al. 2021

Front. Aging Neurosci.

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“…Patients with chronic liver disease may develop mild cognitive and/or motor impairment before reaching cirrhosis, as recently extensively reviewed [14]. Patients with NASH and obesity show mild cognitive impairment (MCI) if their levels of hyperammonemia and inflammation are sufficiently high [15].…”

Section: Introductionmentioning

confidence: 99%

A New Score Unveils a High Prevalence of Mild Cognitive Impairment in Patients with Nonalcoholic Fatty Liver Disease

Giménez-Garzó

Fiorillo

Ballester

et al. 2021

JCM

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Patients with nonalcoholic fatty liver disease (NAFLD) may show mild cognitive impairment (MCI). The neurological functions affected remain unclear. The aims were to: (1) Characterize the neuropsychological alterations in NAFLD patients; (2) assess the prevalence of impairment of neurological functions evaluated; (3) develop a new score for sensitive and rapid MCI detection in NAFLD; (4) assess differences in MCI features between patients with nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH); and (5) compare neuropsychological alterations in NAFLD patients with cirrhotic patients with MCI. Fifty-nine NAFLD patients and 53 controls performed psychometric tests assessing different neurological functions: PHES (Psychometric Hepatic Encephalopathy Score) battery, d2, Stroop, Oral SDMT (Symbol Digit Modalities Test), Digit Span, number-letter test, and bimanual and visual-motor coordination tests. NAFLD patients show impairment in attention, mental concentration, psychomotor speed, cognitive flexibility, inhibitory mental control, and working memory. We developed a new, rapid, and sensitive score based on the most affected parameters in NAFLD patients, unveiling that 32% of NAFLD show MCI. Prevalence was similar in NAFL (36%) or NASH (27%) patients, but lower in NAFLD than in cirrhosis (65%). MCI prevalence is significant in NAFLD patients. Psychometric testing is warranted in these patients to unveil MCI and take appropriate measures to reverse and prevent its progression.

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“…The westernized high-fat diet is believed to cause several diverse health problems, including NAFDL. NAFLD is currently considered as a multisystem disorder manifesting outside the liver itself, and presenting as a wide range of symptoms, from cardiovascular disease to cognitive impairments [ 46 , 47 , 48 ]. To get an insight into a potential relation of HPD-affected S -palmitoylated liver proteins to NAFLD, we analyzed the full lists of the proteins (all 1069 and 1198 proteins for 4- and 12-week livers, respectively) using the NAFLD Gene Set from the Gene Disease Association database.…”

Section: Resultsmentioning

confidence: 99%

“…Palmitic acid is considered a pro-inflammatory agent which, either alone or acting synergistically with LPS, activates TLR4 of macrophages and other cells. The resulting production of pro-inflammatory cytokines contributes to the dysfunction of various organs, including NAFLD [ 24 , 26 , 48 ]. Accordingly, a 16-week feeding of mice a diet with 45% kcal coming from palm oil increased TLR4 and the NLRP3 inflammasome activity in dendritic cells differentiated in vitro from a bone marrow precursor [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Palm Oil-Rich Diet Affects Murine Liver Proteome and S-Palmitoylome

Ziemlińska

Sobocińska

Świątkowska

et al. 2021

IJMS

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Palmitic acid (C16:0) is the most abundant saturated fatty acid in animals serving as a substrate in synthesis and β-oxidation of other lipids, and in the modification of proteins called palmitoylation. The influence of dietary palmitic acid on protein S-palmitoylation remains largely unknown. In this study we performed high-throughput proteomic analyses of a membrane-enriched fraction of murine liver to examine the influence of a palm oil-rich diet (HPD) on S-palmitoylation of proteins. HPD feeding for 4 weeks led to an accumulation of C16:0 and C18:1 fatty acids in livers which disappeared after 12-week feeding, in contrast to an accumulation of C16:0 in peritoneal macrophages. Parallel proteomic studies revealed that HPD feeding induced a sequence of changes of the level and/or S-palmitoylation of diverse liver proteins involved in fatty acid, cholesterol and amino acid metabolism, hemostasis, and neutrophil degranulation. The HPD diet did not lead to liver damage, however, it caused progressing obesity, hypercholesterolemia and hyperglycemia. We conclude that the relatively mild negative impact of such diet on liver functioning can be attributed to a lower bioavailability of palm oil-derived C16:0 vs. that of C18:1 and the efficiency of mechanisms preventing liver injury, possibly including dynamic protein S-palmitoylation.

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Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease—Current Knowledge, Mechanisms and Perspectives

Cited by 59 publications

References 158 publications

Liver Health and Dementia in an Italian Older Population: Findings From the Salus in Apulia Study

Liver Health and Dementia in an Italian Older Population: Findings From the Salus in Apulia Study

A New Score Unveils a High Prevalence of Mild Cognitive Impairment in Patients with Nonalcoholic Fatty Liver Disease

Palm Oil-Rich Diet Affects Murine Liver Proteome and S-Palmitoylome

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