Dataset Information

Association of Altered Liver Enzymes With Alzheimer Disease Diagnosis, Cognition, Neuroimaging Measures, and Cerebrospinal Fluid Biomarkers.

ABSTRACT:

Importance

Increasing evidence suggests an important role of liver function in the pathophysiology of Alzheimer disease (AD). The liver is a major metabolic hub; therefore, investigating the association of liver function with AD, cognition, neuroimaging, and CSF biomarkers would improve the understanding of the role of metabolic dysfunction in AD.

Objective

To examine whether liver function markers are associated with cognitive dysfunction and the "A/T/N" (amyloid, tau, and neurodegeneration) biomarkers for AD.

Design, setting, and participants

In this cohort study, serum-based liver function markers were measured from September 1, 2005, to August 31, 2013, in 1581 AD Neuroimaging Initiative participants along with cognitive measures, cerebrospinal fluid (CSF) biomarkers, brain atrophy, brain glucose metabolism, and amyloid-? accumulation. Associations of liver function markers with AD-associated clinical and A/T/N biomarkers were assessed using generalized linear models adjusted for confounding variables and multiple comparisons. Statistical analysis was performed from November 1, 2017, to February 28, 2019.

Exposures

Five serum-based liver function markers (total bilirubin, albumin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase) from AD Neuroimaging Initiative participants were used as exposure variables.

Main outcomes and measures

Primary outcomes included diagnosis of AD, composite scores for executive functioning and memory, CSF biomarkers, atrophy measured by magnetic resonance imaging, brain glucose metabolism measured by fludeoxyglucose F 18 (18F) positron emission tomography, and amyloid-? accumulation measured by [18F]florbetapir positron emission tomography.

Results

Participants in the AD Neuroimaging Initiative (n?=?1581; 697 women and 884 men; mean [SD] age, 73.4 [7.2] years) included 407 cognitively normal older adults, 20 with significant memory concern, 298 with early mild cognitive impairment, 544 with late mild cognitive impairment, and 312 with AD. An elevated aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio and lower levels of ALT were associated with AD diagnosis (AST to ALT ratio: odds ratio, 7.932 [95% CI, 1.673-37.617]; P?=?.03; ALT: odds ratio, 0.133 [95% CI, 0.042-0.422]; P?=?.004) and poor cognitive performance (AST to ALT ratio: ? [SE], -0.465 [0.180]; P?=?.02 for memory composite score; ? [SE], -0.679 [0.215]; P?=?.006 for executive function composite score; ALT: ? [SE], 0.397 [0.128]; P?=?.006 for memory composite score; ? [SE], 0.637 [0.152]; P?Conclusions and relevanceConsistent associations of serum-based liver function markers with cognitive performance and A/T/N biomarkers for AD highlight the involvement of metabolic disturbances in the pathophysiology of AD. Further studies are needed to determine if these associations represent a causative or secondary role. Liver enzyme involvement in AD opens avenues for novel diagnostics and therapeutics.

SUBMITTER: Nho K

PROVIDER: S-EPMC6669786 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Association of Altered Liver Enzymes With Alzheimer Disease Diagnosis, Cognition, Neuroimaging Measures, and Cerebrospinal Fluid Biomarkers.

Nho Kwangsik K Kueider-Paisley Alexandra A Ahmad Shahzad S MahmoudianDehkordi Siamak S Arnold Matthias M Risacher Shannon L SL Louie Gregory G Blach Colette C Baillie Rebecca R Han Xianlin X Kastenmüller Gabi G Trojanowski John Q JQ Shaw Leslie M LM Weiner Michael W MW Doraiswamy P Murali PM van Duijn Cornelia C Saykin Andrew J AJ Kaddurah-Daouk Rima R

JAMA network open 20190703 7

<h4>Importance</h4>Increasing evidence suggests an important role of liver function in the pathophysiology of Alzheimer disease (AD). The liver is a major metabolic hub; therefore, investigating the association of liver function with AD, cognition, neuroimaging, and CSF biomarkers would improve the understanding of the role of metabolic dysfunction in AD.<h4>Objective</h4>To examine whether liver function markers are associated with cognitive dysfunction and the "A/T/N" (amyloid, tau, and neurod ...[more]

PMID: 31365104

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Project description:African Americans have been reported to have a higher prevalence of Alzheimer's disease (AD) than Caucasians, but etiology-specific AD biomarkers have not been systematically analyzed in older African Americans. Coexisting cerebrovascular disease may also contribute to this increased prevalence. We hypothesized that cerebrospinal fluid (CSF) biomarkers of amyloid, neurodegeneration, and endothelial dysfunction would differ between older African Americans and Caucasians with normal cognition and cognitive impairment associated with AD.We prospectively recruited 135 older Americans to undergo detailed clinical, neuropsychological, genetic, magnetic resonance imaging (MRI), and CSF analysis from 2013 to 2015 at Emory University (Atlanta, GA, USA). We compared levels of CSF markers for ?-amyloid (A?42, A?40), total and phosphorylated tau (t-tau and p-tau181, respectively), endothelial dysfunction (soluble vascular cell adhesion molecule 1, soluble intercellular adhesion molecule 1), ?-synuclein, and neurodegeneration (neurofilament light chain [NfL]), as well as MRI markers, for hippocampal atrophy and cerebrovascular disease (white matter hyperintensity [WMH] volume).Sixty-five older African Americans (average age, 69.1 years) and 70 older Caucasians (average age, 70.8 years) were included. After adjusting for demographic variables, AD risk alleles, and cognitive function, older African Americans had lower CSF levels of p-tau181 (difference of 7.4 pg/ml; 95% CI, 3.7-11.2 pg/ml; p?<?0.001), t-tau (difference of 23.6 pg/ml; 95% CI, 9.5-37.7; p?=?0.001), and A?40 (difference of 1.35 ng/ml; 95% CI, 0.29-2.42 ng/ml; p?=?0.013) despite similar levels of A?42, NfL, WMH volume, and hippocampal volume. Cognitively impaired African Americans also had lower CSF t-tau/A?42 (difference of 0.255 per 1-SD change in composite cognition; 95% CI, 0.100-0.409; p?=?0.001) and p-tau181/A?42 (difference of 0.076 per 1-SD change in composite cognition; 95% CI, 0.031-0.122; p?=?0.001). These could not be explained by measured biomarkers of non-AD processes, but African Americans may be more susceptible than Caucasians to the cognitive effects of WMH.Despite comparable levels of CSF A?42 and A?42/A?40, cognitive impairment in African Americans is associated with smaller changes in CSF tau markers but greater impact from similar WMH burden than Caucasians. Race-associated differences in CSF tau markers and ratios may lead to underdiagnosis of AD in African Americans.ClinicalTrials.gov, NCT02089555 . Retrospectively registered on 14 March 2014.

Dataset Information

Association of Altered Liver Enzymes With Alzheimer Disease Diagnosis, Cognition, Neuroimaging Measures, and Cerebrospinal Fluid Biomarkers.

Importance

Objective

Design, setting, and participants

Exposures

Main outcomes and measures

Results

Publications

Association of Altered Liver Enzymes With Alzheimer Disease Diagnosis, Cognition, Neuroimaging Measures, and Cerebrospinal Fluid Biomarkers.

Similar Datasets

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