Evidence map›Paper›PMID 30337151›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2019

Altered bile acid profile associates with cognitive impairment in Alzheimer's disease-An emerging role for gut microbiome.

Siamak MahmoudianDehkordi, Matthias Arnold, Kwangsik Nho, Shahzad Ahmad, Wei Jia, Guoxiang Xie, Gregory Louie, Alexandra Kueider-Paisley, M Arthur Moseley, J Will Thompson and 27 more

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 415 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
415citing papers in PubMed, 4 pooled it
19.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

415 citing papers in PubMed, 4 syntheses or guidelines pooled it, 664 citations in OpenAlex.

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355 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

37 authors at 20 institutions in 5 countries.

Siamak MahmoudianDehkordiDepartment of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
Matthias ArnoldDepartment of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA; Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Kwangsik NhoDepartment of Radiology and Imaging Sciences and the Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Shahzad AhmadDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands.
Wei JiaUniversity of Hawaii Cancer Center, Honolulu, HI, USA; Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Guoxiang XieUniversity of Hawaii Cancer Center, Honolulu, HI, USA.
Gregory LouieDepartment of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
Alexandra Kueider-PaisleyDepartment of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
M Arthur MoseleyDuke Proteomics and Metabolomics Shared Resource, Center for Genomic and Computational Biology, Durham, NC, USA.
J Will ThompsonDuke Proteomics and Metabolomics Shared Resource, Center for Genomic and Computational Biology, Durham, NC, USA.
Lisa St John WilliamsDuke Proteomics and Metabolomics Shared Resource, Center for Genomic and Computational Biology, Durham, NC, USA.
Jessica D TenenbaumDepartment of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
Colette BlachDuke Molecular Physiology Institute, Duke University, Durham, NC, USA.
Rebecca BaillieRosa & Co LLC, San Carlos, CA, USA.
Xianlin HanUniversity of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Sudeepa BhattacharyyaDepartment of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Jon B ToledoDepartment of Neurology, Houston Methodist Hospital, Houston, TX, USA.
Simon SchaffererBIOCRATES Life Sciences AG, Innsbruck, Austria.
Sebastian KleinBIOCRATES Life Sciences AG, Innsbruck, Austria.
Therese KoalBIOCRATES Life Sciences AG, Innsbruck, Austria.
Shannon L RisacherDepartment of Radiology and Imaging Sciences and the Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Mitchel Allan KlingBehavioral Health Service, Crescenz VA Medical Center and Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Alison Motsinger-ReifBioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC, USA.
Daniel M RotroffBioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC, USA.
John JackBioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC, USA.
Thomas HankemeierDivision of Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden University, RA Leiden, The Netherlands.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Philip L De JagerColumbia University College of Physicians and Surgeons Department of Neurology, Center for Translational & Computational Neuroimmunology, New York, NY, USA.
John Q TrojanowskiDepartment of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Leslie M ShawDepartment of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Michael W WeinerCenter for Imaging of Neurodegenerative Diseases, Department of Radiology, San Francisco VA Medical Center/University of California San Francisco, San Francisco, CA, USA.
P Murali DoraiswamyDepartment of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA; Duke Institute of Brain Sciences, Duke University, Durham, NC, USA; Department of Medicine, Duke University, Durham, NC, USA.
Cornelia M van DuijnDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands.
Andrew J SaykinDepartment of Radiology and Imaging Sciences and the Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: asaykin@iupui.edu.
Gabi KastenmüllerInstitute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany. Electronic address: g.kastenmueller@helmholtz-muenchen.de.
Rima Kaddurah-DaoukDepartment of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA; Duke Institute of Brain Sciences, Duke University, Durham, NC, USA; Department of Medicine, Duke University, Durham, NC, USA. Electronic address: kaddu001@mc.duke.edu.
Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium
Duke University · USAbterra Biosciences (United States) · USBiocrates Life Sciences (Austria) · ATNorth Carolina State University · USErasmus University Rotterdam · NLIndiana University – Purdue University Indianapolis · USUniversity of Pennsylvania · USAnalytical Biosciences (China) · CNColumbia University · USHeinrich Heine University Düsseldorf · DEHelmholtz Zentrum München · DEIndiana University School of MedicineMethodist Hospital · USPhiladelphia VA Medical Center · USRosa (United States) · USRush University Medical Center · USSan Francisco VA Medical Center · USShanghai Jiao Tong University · CNThe University of Texas Health Science Center at San Antonio · USUniversity of Arkansas for Medical Sciences · US

Funding

Project 1U19AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI MICHAEL W WEINER · 2016 to 2026
$226.7M
Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI LEURGANS, SUE E. · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
Research Education ComponentP30AG010133 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SAYKIN, ANDREW J · 1991 to 2020
$37.3M
UPenn ADCC Biomarker CoreP30AG010124 · NIA · UNIVERSITY OF PENNSYLVANIA · PI DETRE, JOHN A · 1991 to 2020
$35.1M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Project IV: "Alpha-Synuclein Strains & Diverse Synucleinopathies"P50NS053488 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI TROJANOWSKI, JOHN Q. · 2007 to 2017
$20.9M
Pathway discovery, validation and compound identification for Alzheimer's disease - SupplementU01AG046152 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2013 to 2017
$13.6M
Metabolomic Signatures for Disease Sub-classification and Target Prioritization in AMP-ADU01AG061359 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F, KASTENMULLER, GABI · 2018 to 2022
$10.0M
Collaborative Applied StatisticsZIAES103335 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI MOTSINGER-REIF, ALISON · 2019 to 2025
$9.0M
Memory Circuitry in MCI and Early Alzheimer’s Disease Prodrome: Molecular DriversR01AG019771 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SAYKIN, ANDREW J · 2001 to 2021
$6.9M
NIA NIH HHS K01 AG049050NIA NIH HHS P30 AG010124NIA NIH HHS P30 AG010133NIA NIH HHS P30 AG010161NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG019771NIA NIH HHS R01 AG046171NIA NIH HHS R01 AG048015NIA NIH HHS R03 AG054936NIA NIH HHS RF1 AG051550NIA NIH HHS RF1 AG057452NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG061359NIA NIH HHS U19 AG024904NIBIB NIH HHS R01 EB022574NIMH NIH HHS R01 MH098260NINDS NIH HHS P50 NS053488NLM NIH HHS K99 LM011384NLM NIH HHS R00 LM011384NLM NIH HHS R01 LM011360NLM NIH HHS R01 LM012535
6 · The paper itself

Abstract

introductionIncreasing evidence suggests a role for the gut microbiome in central nervous system disorders and a specific role for the gut-brain axis in neurodegeneration. Bile acids (BAs), products of cholesterol metabolism and clearance, are produced in the liver and are further metabolized by gut bacteria. They have major regulatory and signaling functions and seem dysregulated in Alzheimer's disease (AD).

methodsSerum levels of 15 primary and secondary BAs and their conjugated forms were measured in 1464 subjects including 370 cognitively normal older adults, 284 with early mild cognitive impairment, 505 with late mild cognitive impairment, and 305 AD cases enrolled in the AD Neuroimaging Initiative. We assessed associations of BA profiles including selected ratios with diagnosis, cognition, and AD-related genetic variants, adjusting for confounders and multiple testing.

resultsIn AD compared to cognitively normal older adults, we observed significantly lower serum concentrations of a primary BA (cholic acid [CA]) and increased levels of the bacterially produced, secondary BA, deoxycholic acid, and its glycine and taurine conjugated forms. An increased ratio of deoxycholic acid:CA, which reflects 7α-dehydroxylation of CA by gut bacteria, strongly associated with cognitive decline, a finding replicated in serum and brain samples in the Rush Religious Orders and Memory and Aging Project. Several genetic variants in immune response-related genes implicated in AD showed associations with BA profiles. DISCUSSION: We report for the first time an association between altered BA profile, genetic variants implicated in AD, and cognitive changes in disease using a large multicenter study. These findings warrant further investigation of gut dysbiosis and possible role of gut-liver-brain axis in the pathogenesis of AD.

Indexed as

Alzheimer DiseaseGastrointestinal MicrobiomeAgedBile Acids and SaltsCognitive DysfunctionDysbiosisFemaleHumansLiverMaleMetabolomeBile Acids and SaltsAlzheimer's diseaseAtlas for AlzheimerGenetic variantsGut-liver-brain axisGut microbiomeImmunityInflammationLipidomicsMetabolomeMetabolomics

Identifiers

PMID30337151
PMCPMC6487485
OpenAlexW2794227656

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.