Evidence map›Paper›PMID 38076824›Full record

ArticlemedRxiv : the preprint server for health sciences2023

A Modified Mediterranean Ketogenic Diet mitigates modifiable risk factors of Alzheimer's Disease: a serum and CSF-based metabolic analysis.

Annalise Schweickart, Richa Batra, Bryan J Neth, Cameron Martino, Liat Shenhav, Anru R Zhang, Pixu Shi, Naama Karu, Kevin Huynh, Peter J Meikle and 11 more

Open access · greenAbstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Symposium: What Does the Microbiome Tell Us about Prevention and Treatment of AD/ADRD?The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 9 institutions in 3 countries.

Annalise SchweickartTri-Institutional Program in Computational Biology & Medicine, Weill Cornell Medicine, New York, NY, USA.ORCID 0000-0001-9691-3741
Richa BatraDepartment of Physiology and Biophysics, Weill Cornell Medicine, Institute for Computational Biomedicine, Englander Institute for Precision Medicine, New York, NY 10021, USA.ORCID 0000-0003-3708-0086
Bryan J NethDepartment of Neurology, Mayo Clinic, Rochester, MN.
Cameron MartinoDepartment of Pediatrics, University of California San Diego, La Jolla, CA.
Liat ShenhavDepartment of Microbiology, New York University Grossman School of Medicine, New York, NY, USA.
Anru R ZhangDepartment of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
Pixu ShiDepartment of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
Naama KaruTasmanian Independent Metabolomics and Analytical Chemistry Solutions (TIMACS), Hobart, 7008 Tasmania, Australia.
Kevin HuynhBaker Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC, Australia.
Peter J MeikleBaker Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC, Australia.
Leyla SchimmelDepartment of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
Amanda Hazel DilmoreDepartment of Pediatrics, University of California San Diego, La Jolla, CA.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden.
Colette BlachDuke Molecular Physiology Institute, Duke University, Durham, NC, USA.
Pieter C DorresteinSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA.
Rob KnightDepartments of Pediatrics, Computer Science and Engineering, Bioengineering, University of California San Diego, La Jolla, CA.
Alzheimer’s Gut Microbiome Project Consortium
Suzanne CraftDepartment of Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA.
Rima Kaddurah-DaoukDepartment of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
Jan KrumsiekDepartment of Physiology and Biophysics, Weill Cornell Medicine, Institute for Computational Biomedicine, Englander Institute for Precision Medicine, New York, NY 10021, USA.ORCID 0000-0003-4734-3791
Duke University · USUniversity of California San Diego · USCornell University · USBaker Heart and Diabetes Institute · AUUniversity of Gothenburg · SEMayo Clinic in Arizona · USNew York University · USUniversity of Tasmania · AUWake Forest University · US

Funding

National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
Project 4 - Mechanistic studies on the role of the gut microbiome in models for Alzheimer's diseaseU19AG063744 · NIA · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Rima F Kaddurah-Daouk · 2019 to 2026
$54.1M
Wake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3M
Wake Forest University School of Medicine Alzheimer's Disease Research CenterP30AG072947 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI SUZANNE CRAFT · 2021 to 2026
$24.3M
Wake Forest Alzheimer's Disease Core CenterP30AG049638 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI WILLIAMSON, JEFF DOUGLAS · 2016 to 2020
$12.2M
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
Metabolic Signatures Underlying Vascular Risk Factors for Alzheimer-type DementiasRF1AG051550 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F, KLING, MITCHEL ALLAN · 2015 to 2016
$6.3M
Metabolic Networks and Pathways Predictive of Sex Differences in AD Risk and Responsiveness to TreatmentRF1AG059093 · NIA · DUKE UNIVERSITY · PI BRINTON, ROBERTA EILEEN, CHANG, RUI · 2018 to 2018
$5.9M
Metabolic Networks and Pathways in Alzheimer's DiseaseR01AG046171 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F · 2014 to 2017
$4.4M
TargetAD: A systems multi-omics approach to drug repositioning in Alzheimer's diseaseR01AG069901 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI Matthias Arnold, Jan Krumsiek · 2021 to 2026
$3.7M
Metabolic Network Analysis of Biochemical Trajectories in Alzheimer's DiseaseRF1AG057452 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F, KASTENMULLER, GABI · 2017 to 2017
$3.5M
Gut Liver Brain Biochemical Axis in Alzheimer's DiseaseRF1AG058942 · NIA · DUKE UNIVERSITY · PI KADDURAH-DAOUK, RIMA F, VAN DUIJN, CORNELIA MARJA · 2018 to 2018
$3.4M
NCATS NIH HHS UL1 TR001420NIA NIH HHS P30 AG049638NIA NIH HHS P30 AG072947NIA NIH HHS R01 AG046171NIA NIH HHS R01 AG069901NIA NIH HHS RF1 AG051550NIA NIH HHS RF1 AG057452NIA NIH HHS RF1 AG058942NIA NIH HHS RF1 AG059093NIA NIH HHS U01 AG061359NIA NIH HHS U19 AG063744NIA NIH HHS U24 AG021886
6 · The paper itself

Abstract

Alzheimer's disease (AD) is influenced by a variety of modifiable risk factors, including a person's dietary habits. While the ketogenic diet (KD) holds promise in reducing metabolic risks and potentially affecting AD progression, only a few studies have explored KD's metabolic impact, especially on blood and cerebrospinal fluid (CSF). Our study involved participants at risk for AD, either cognitively normal or with mild cognitive impairment. The participants consumed both a modified Mediterranean-ketogenic diet (MMKD) and the American Heart Association diet (AHAD) for 6 weeks each, separated by a 6-week washout period. We employed nuclear magnetic resonance (NMR)-based metabolomics to profile serum and CSF and metagenomics profiling on fecal samples. While the AHAD induced no notable metabolic changes, MMKD led to significant alterations in both serum and CSF. These changes included improved modifiable risk factors, like increased HDL-C and reduced BMI, reversed serum metabolic disturbances linked to AD such as a microbiome-mediated increase in valine levels, and a reduction in systemic inflammation. Additionally, the MMKD was linked to increased amino acid levels in the CSF, a breakdown of branched-chain amino acids (BCAAs), and decreased valine levels. Importantly, we observed a strong correlation between metabolic changes in the CSF and serum, suggesting a systemic regulation of metabolism. Our findings highlight that MMKD can improve AD-related risk factors, reverse some metabolic disturbances associated with AD, and align metabolic changes across the blood-CSF barrier.

Identifiers

PMID38076824
PMCPMC10705656
OpenAlexW4389094599

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.