Evidence map›Paper›PMID 22431837›Full record

Trial reportArchives of neurology2012

Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures.

Douglas R Galasko, Elaine Peskind, Christopher M Clark, Joseph F Quinn, John M Ringman, Gregory A Jicha, Carl Cotman, Barbara Cottrell, Thomas J Montine, Ronald G Thomas and 2 more

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Archives of neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00117403 (Evaluation of the Safety, Tolerability and Impact on Biomarkers of Anti-Oxidant Treatment of Mild to Moderate Alzheimer's Disease), which is not on this map. Cited by 192 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
192citing papers in PubMed, 11 pooled it
19.6field-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.

NCT00117403 phase1completednot on this map

Evaluation of the Safety, Tolerability and Impact on Biomarkers of Anti-Oxidant Treatment of Mild to Moderate Alzheimer's Disease

TypeinterventionalSponsorNational Institute on Aging (NIA)Ran2006 to 2007Enrolled75ConditionsAlzheimer's DiseaseArmsVitamin E, Vitamin C, and Alpha-lipoic Acid, Coenzyme Q, Placebo capsules, Placebo wafers
3 · Its place in the literature

Who cites it

192 citing papers in PubMed, 11 syntheses or guidelines pooled it, 366 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Pooled it
  10. Vitamin E for Alzheimer's dementia and mild cognitive impairment.The Cochrane database of systematic reviews · 2017
    Pooled it
  11. Vitamin E for Alzheimer's dementia and mild cognitive impairment.The Cochrane database of systematic reviews · 2017
    Pooled it
  12. Trial
  13. Trial
  14. Trial
  15. Trial
  16. Trial
  17. Trial
  18. Review
  19. Article
  20. Review

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 7 institutions in 1 country.

Douglas R GalaskoDepartment of Neurosciences, University of California, San Diego, 92093, USA. dgalasko@ucsd.edu
Elaine Peskind
Christopher M Clark
Joseph F Quinn
John M Ringman
Gregory A Jicha
Carl Cotman
Barbara Cottrell
Thomas J Montine
Ronald G Thomas
Paul Aisen
Alzheimer’s Disease Cooperative Study
University of California, San Diego · USUniversity of Washington · USEli Lilly (United States) · USOregon Health & Science University · USUniversity of California, Irvine · USUniversity of California, Los Angeles · USUniversity of Kentucky · US

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
TRIAL OF VALPROATE TO ATTENUATE THE PROGRESSION OF ADU01AG010483 · NIA · UNIVERSITY OF ROCHESTER · PI AISEN, PAUL S. · 1991 to 2012
$116.2M
RECRUITMENT COREU19AG010483 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FELDMAN, HOWARD · 2013 to 2020
$80.6M
Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4M
THERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI GRABOWSKI, THOMAS J. · 1985 to 2019
$57.2M
VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BREWER, JAMES B · 1985 to 2018
$55.4M
UC Irvine Alzheimer's Disease Research Center Induced Pluripotent Stem Cell CoreP50AG016573 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 2000 to 2019
$37.0M
UCLA ALZHEIMERS DISEASE RESEARCH CENTERP50AG016570 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CUMMINGS, JEFFREY L. · 1999 to 2014
$25.9M
TISSUE REPOSITORY COREP01AG000538 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 1985 to 2018
$24.8M
University of Kentucky Alzheimer's Disease Core Center - Biomarker CoreP30AG028383 · NIA · UNIVERSITY OF KENTUCKY · PI GOLD, BRIAN TIMOTHY, VAN ELDIK, LINDA J · 2006 to 2020
$23.3M
Udall Center Director's meeting poster awardP50NS062684 · NINDS · UNIVERSITY OF WASHINGTON · PI MONTINE, THOMAS J · 2009 to 2020
$18.3M
Prevention of Alzheimer's Diseae by Vitamin E and SeleniumR01AG019241 · NIA · UNIVERSITY OF KENTUCKY · PI SCHMITT, FREDERICK · 2001 to 2012
$12.1M
NIAMS NIH HHS AR47752NIAMS NIH HHS T32 AR047752NIA NIH HHS AG000096NIA NIH HHS AG00538NIA NIH HHS AG016573NIA NIH HHS L30 AG032934NIA NIH HHS L30AG032934NIA NIH HHS P01 AG000538NIA NIH HHS P30 AG028383NIA NIH HHS P30AG028383NIA NIH HHS P50 AG005131NIA NIH HHS P50 AG005136NIA NIH HHS P50 AG016570NIA NIH HHS P50 AG016573NIA NIH HHS P50AG16570NIA NIH HHS R01 AG016381NIA NIH HHS R01 AG019241NIA NIH HHS R01AG019241NIA NIH HHS R01 AG030048NIA NIH HHS R01 AG031892NIA NIH HHS R01 AG033133NIA NIH HHS R01 AG16381NIA NIH HHS R01 AG31892NIA NIH HHS T32 AG000096NIA NIH HHS U01 AG010483NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG032438NIA NIH HHS U01AG032438NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG10483NIA NIH HHS U01AG10483NIA NIH HHS U01 AG32984NIA NIH HHS U19 AG010483NIA NIH HHS UO1 AG10483NICHD NIH HHS R01 HD064993-0110NIEHS NIH HHS R01 ES016754NIEHS NIH HHS R01 ES16754NIEHS NIH HHS T32 ES007032NIEHS NIH HHS T32 ES07032NINDS NIH HHS P50 NS062684NINDS NIH HHS P50 NS62684PHS HHS P50AGO0817PHS HHS P50AGO5131PHS HHS P50 AGO5136PHS HHS R01 AGO33133
6 · The paper itself

Abstract

objectiveTo evaluate whether antioxidant supplements presumed to target specific cellular compartments affected cerebrospinal fluid (CSF) biomarkers.

designDouble-blind, placebo-controlled clinical trial.

settingAcademic medical centers.

participantsSubjects with mild to moderate Alzheimer disease.

interventionRandom assignment to treatment for 16 weeks with 800 IU/d of vitamin E (α-tocopherol) plus 500 mg/d of vitamin C plus 900 mg/d of α-lipoic acid (E/C/ALA); 400 mg of coenzyme Q 3 times/d; or placebo.

main outcome measuresChanges from baseline to 16 weeks in CSF biomarkers related to Alzheimer disease and oxidative stress, cognition (Mini-Mental State Examination), and function (Alzheimer's Disease Cooperative Study Activities of Daily Living Scale).

resultsSeventy-eight subjects were randomized; 66 provided serial CSF specimens adequate for biochemical analyses. Study drugs were well tolerated, but accelerated decline in Mini-Mental State Examination scores occurred in the E/C/ALA group, a potential safety concern. Changes in CSF Aβ42, tau, and P-tau(181) levels did not differ between the 3 groups. Cerebrospinal fluid F2-isoprostane levels, an oxidative stress biomarker, decreased on average by 19% from baseline to week 16 in the E/C/ALA group but were unchanged in the other groups.

conclusionsAntioxidants did not influence CSF biomarkers related to amyloid or tau pathology. Lowering of CSF F2-isoprostane levels in the E/C/ALA group suggests reduction of oxidative stress in the brain. However, this treatment raised the caution of faster cognitive decline, which would need careful assessment if longer-term clinical trials are conducted.

trial registrationclinicaltrials.gov Identifier: NCT00117403.

Indexed as

Dietary SupplementsActivities of Daily LivingAgedAged, 80 and overalpha-TocopherolAlzheimer DiseaseAmyloid beta-PeptidesAntioxidantsAscorbic AcidBiomarkersCholinesterase InhibitorsDouble-Blind MethodF2-IsoprostanesFemaleFollow-Up StudiesHumansalpha-TocopherolAmyloid beta-Peptidesamyloid beta-protein (1-42)AntioxidantsAscorbic AcidBiomarkersCholinesterase Inhibitorscoenzyme Q10F2-IsoprostanesMemantinePeptide Fragmentstau ProteinsThioctic AcidUbiquinone

Identifiers

PMID22431837
PMCPMC3661272
OpenAlexW2142439044

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.