Liver Enzymes in a Cohort of Community-Dwelling Older Persons: Focus on Sex Contribution

Ferri, Evelyn; Rossi, Paolo; Scichilone, Martina; Lucchi, Tiziano; Arosio, Beatrice

doi:10.3390/nu14234973

Cited by 11 publications

(12 citation statements)

References 58 publications

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“…While an increase in serum AST and ALT levels often holds clinical signi cance as hepatocyte membrane damage can release these enzymes into the bloodstream [34], previous studies have reported that lower AST and ALT levels within their normal ranges and a higher AST-to-ALT ratio were associated with AD diagnosis, poor cognitive performance, and increased Aβ deposition [7][8][9][10][11]. Our results are generally consistent with these earlier ndings.…”

Section: Discussionsupporting

confidence: 90%

“…Nho et al reported a signi cant association between a higher aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio and lower blood ALT levels with AD diagnosis, poor cognitive performance, and increased Aβ deposition [7]. Likewise, other studies have found that lower AST and ALT levels, along with a higher AST to ALT ratio were associated with AD diagnosis and poor cognitive performance [8][9][10][11]. However, despite these intriguing associations, there remains a lack of consensus among studies on the precise relationship between blood AST and ALT levels and AD, as evidenced by Kamada et al, who reported signi cant negative correlations between plasma AST and ALT levels and cognitive decline [12].…”

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confidence: 99%

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Implications of serum liver enzymes for brain amyloidopathy and cognition

Han,

Lee,

Kim

et al. 2023

Preprint

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Background Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) plaque accumulation and neurofibrillary tangles in the brain. Emerging evidence has suggested potential interactions between the brain and peripheral organs, particularly the liver, in regulating Aβ homeostasis. This study aimed to investigate the association of serum liver enzymes with brain amyloidopathy and cognitive performance as the precise relationship remains unclear. Methods This retrospective study analyzed data collected between November 2015 and June 2023 using a clinical big data analytic solution called the Smart Clinical Data Warehouse (CDW). A total of 1,036 patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD dementia, and other neurodegenerative diseases were included in the study. Amyloid positron emission tomography (PET) imaging, comprehensive neuropsychological evaluations, and measurements of liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, and albumin, were assessed. Logistic and linear regression analyses were used to investigate the associations between liver enzymes, amyloid status, and cognitive performance. Additionally, a machine learning approach was used to assess the classification performance of liver enzymes in predicting amyloid status. Results Lower ALT levels (OR, 0.976; 95% CI, 0.957–0.994; P = 0.031) and higher AST-to-ALT ratios (OR, 1.862; 95% CI, 1.397–2.521; P < 0.001) were significantly associated with amyloid PET positivity. The AST-to-ALT ratio wasalsosignificantly associated with poor memory function. Machine learning analysis revealed that the classification performance of amyloid status (area under the curve (AUC) = 0.642) for age, sex, and apolipoprotein E ε4 carrier status significantly improved by 6.2% by integrating the AST-to-ALT ratio. Conclusions The association of lower ALT levels and a higher AST-to-ALT ratio with amyloid status in the brain suggests potential implications of liver function in the Aβ pathogenesis of AD. Moreover, the AST-to-ALT ratio showed promising associations with memory function, and its integration with clinical information improved the classification performance of amyloid status in the brain.

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Section: Discussionsupporting

confidence: 90%

mentioning

confidence: 99%

Implications of serum liver enzymes for brain amyloidopathy and cognition

Han,

Lee,

Kim

et al. 2023

Preprint

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“…These findings suggest that reduced ALT levels may contribute to decreased pyruvate levels, leading to disrupted energy balance, compromised glutamate metabolism, and impaired synaptic transmission in the central nervous system. However, it's important to note that Ferri et al (2022) only observed lower serum ALT levels and higher AST/ALT ratios in elderly male dementia patients compared to cognitively normal individuals, with no significant differences observed in elderly females. In contrast, a study by Yokokawa et al (2022) found a significant correlation between serum levels of brain-derived neurotrophic factor (BDNF) and liver enzymes in middle-aged and elderly females, along with a negative correlation between BDNF and liver fibrosis measured by the Fibrosis-4 (FIB-4) index.…”

Section: Liver-derived Factorsmentioning

confidence: 84%

Regulation of mild cognitive impairment associated with liver disease by humoral factors derived from the gastrointestinal tract and MRI research progress: a literature review

et al. 2023

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Patients with liver disease are prone to various cognitive impairments. It is undeniable that cognitive impairment is often regulated by both the nervous system and the immune system. In this review our research focused on the regulation of mild cognitive impairment associated with liver disease by humoral factors derived from the gastrointestinal tract, and revealed that its mechanisms may be involved with hyperammonemia, neuroinflammation, brain energy and neurotransmitter metabolic disorders, and liver-derived factors. In addition, we share the emerging research progress in magnetic resonance imaging techniques of the brain during mild cognitive impairment associated with liver disease, in order to provide ideas for the prevention and treatment of mild cognitive impairment in liver disease.

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“…For instance, Huynh et al reported that the deletion of ApoE in the hepatocytes of APP/PS1 mice, resulting in decreased plasma ApoE levels but no change in brain ApoE levels, did not in uence the amount of amyloid plaques [65]. Furthermore, there is supporting evidence that serum-based liver function markers, including AST, ALT, and ALP levels and the AST to ALT ratio, are associated with AD diagnosis, poor cognitive performance, and increased Aβ deposition [6][7][8][9][10][11]. Additionally, there is a lack of studies investigating the effects of the APOE ε4 allele on the association of liver function markers with AD pathogenesis and cognition in humans.…”

Section: Discussionmentioning

confidence: 99%

Influence of liver function markers and apolipoprotein E ε4 on pathogenesis and cognitive decline in Alzheimer’s disease

Han,

Lee,

Kim

et al. 2023

Preprint

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Background Alzheimer’s disease (AD) is a complex neurodegenerative disorder influenced by various factors, including liver function, which may impact the clearance of amyloid-β (Aβ) in the brain. This study aimed to explore how the apolipoprotein E (APOE) ε4 allele, a well-known genetic risk factor for AD, affects the relationship of liver function markers with AD pathology and cognition.Methods Using two independent cohorts, the Hallym University Medical Center and the Alzheimer’s Disease Neuroimaging Initiative, logistic and linear regression models were used to investigate the associations of liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, total bilirubin, and albumin) with AD diagnosis, amyloid positron emission tomography (PET) burden, cerebrospinal fluid biomarkers for AD (Aβ42, total tau, and phosphorylated tau181]), and cognitive performance. Mediation analyses were conducted to assess whether age and amyloid PET burden mediated these associations.Results Only in the APOE ε4 carrier group, a high AST to ALT ratio and low ALT levels were significantly associated with AD diagnosis, increased amyloid PET burden, poor cognitive function at the last visit, and faster longitudinal decline in cognitive function in both cohorts. However, no such relationship was observed in the APOE ε4 non-carrier group. In particular, the AST to ALT ratio was associated with cerebrospinal fluid Aβ42 levels exclusively in the APOE ε4 carrier group in the Alzheimer's Disease Neuroimaging Initiative cohort but not with phosphorylated tau181 or total tau levels. Moreover, mediation analyses in both cohorts revealed that age played a mediating role in the associations between these liver enzymes and amyloid PET burden or AD diagnosis, exclusively in the APOE ε4 non-carrier group, but not in the APOE ε4 carrier group. The association between these liver enzymes and AD diagnosis was mediated by the amyloid PET burden, but this mediation effect was only evident in the APOE ε4 carrier group.Conclusions This study provides valuable insights into the significant influence of the APOE ε4 allele on the intricate relationships of liver enzymes with Aβ-related pathogenesis and cognition in AD. Further research is required to elucidate the underlying mechanisms and potential therapeutic implications of these findings.

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Liver Enzymes in a Cohort of Community-Dwelling Older Persons: Focus on Sex Contribution

Cited by 11 publications

References 58 publications

Implications of serum liver enzymes for brain amyloidopathy and cognition

Implications of serum liver enzymes for brain amyloidopathy and cognition

Regulation of mild cognitive impairment associated with liver disease by humoral factors derived from the gastrointestinal tract and MRI research progress: a literature review

Influence of liver function markers and apolipoprotein E ε4 on pathogenesis and cognitive decline in Alzheimer’s disease

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