Evidence map›Paper›PMID 30952794›Full record

Trial reportNeurology2019

INTREPAD: A randomized trial of naproxen to slow progress of presymptomatic Alzheimer disease.

Pierre-François Meyer, Jennifer Tremblay-Mercier, Jeannie Leoutsakos, Cécile Madjar, Marie-Elyse Lafaille-Magnan, Melissa Savard, Pedro Rosa-Neto, Judes Poirier, Pierre Etienne, John Breitner and 1 more

Erratum issuedOpen access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Neurology, 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 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
6.9field-weighted citation impact, top 2% 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

66 citing papers in PubMed, 112 citations in OpenAlex.

  1. Trial
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  4. No apparent effect of naproxen on CSF markers of innate immune activation.Annals of clinical and translational neurology · 2019
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  5. Article
  6. Review
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  10. Article
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  12. The PREVENT-AD cohort: Accelerating Alzheimer's disease research and treatment in Canada and beyond.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  13. Neuroinflammation in Alzheimer disease.Nature reviews. Immunology · 2025
    Review
  14. Immune modulation to treat Alzheimer's disease.Molecular neurodegeneration · 2025
    Review
  15. Precuneus Activity during Retrieval Is Positively Associated with Amyloid Burden in Cognitively Normal OlderThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  16. Review
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6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 2 countries.

Pierre-François MeyerFrom the McGill Centre for Integrative Neuroscience, Montreal Neurological Institute (C.M.), and McGill University Research Centre for Studies in Aging (M.S., P.R.-N.), McGill University (P.-F.M., M.-E.L.-M., P.R.-N., J.P., P.E., J.B.); StoP-AD Centre (P.-F.M., J.T.-M., M.-E.L.-M., P.R.-N., J.P., P.E., J.B.), Douglas Mental Health University Institute Research Centre, Montréal, Canada; and John Hopkins University (J.L.), Baltimore, MD.
Jennifer Tremblay-MercierFrom the McGill Centre for Integrative Neuroscience, Montreal Neurological Institute (C.M.), and McGill University Research Centre for Studies in Aging (M.S., P.R.-N.), McGill University (P.-F.M., M.-E.L.-M., P.R.-N., J.P., P.E., J.B.); StoP-AD Centre (P.-F.M., J.T.-M., M.-E.L.-M., P.R.-N., J.P., P.E., J.B.), Douglas Mental Health University Institute Research Centre, Montréal, Canada; and John Hopkins University (J.L.), Baltimore, MD.
Jeannie LeoutsakosFrom the McGill Centre for Integrative Neuroscience, Montreal Neurological Institute (C.M.), and McGill University Research Centre for Studies in Aging (M.S., P.R.-N.), McGill University (P.-F.M., M.-E.L.-M., P.R.-N., J.P., P.E., J.B.); StoP-AD Centre (P.-F.M., J.T.-M., M.-E.L.-M., P.R.-N., J.P., P.E., J.B.), Douglas Mental Health University Institute Research Centre, Montréal, Canada; and John Hopkins University (J.L.), Baltimore, MD.
Cécile MadjarFrom the McGill Centre for Integrative Neuroscience, Montreal Neurological Institute (C.M.), and McGill University Research Centre for Studies in Aging (M.S., P.R.-N.), McGill University (P.-F.M., M.-E.L.-M., P.R.-N., J.P., P.E., J.B.); StoP-AD Centre (P.-F.M., J.T.-M., M.-E.L.-M., P.R.-N., J.P., P.E., J.B.), Douglas Mental Health University Institute Research Centre, Montréal, Canada; and John Hopkins University (J.L.), Baltimore, MD.
Marie-Elyse Lafaille-MagnanFrom the McGill Centre for Integrative Neuroscience, Montreal Neurological Institute (C.M.), and McGill University Research Centre for Studies in Aging (M.S., P.R.-N.), McGill University (P.-F.M., M.-E.L.-M., P.R.-N., J.P., P.E., J.B.); StoP-AD Centre (P.-F.M., J.T.-M., M.-E.L.-M., P.R.-N., J.P., P.E., J.B.), Douglas Mental Health University Institute Research Centre, Montréal, Canada; and John Hopkins University (J.L.), Baltimore, MD.
Melissa SavardFrom the McGill Centre for Integrative Neuroscience, Montreal Neurological Institute (C.M.), and McGill University Research Centre for Studies in Aging (M.S., P.R.-N.), McGill University (P.-F.M., M.-E.L.-M., P.R.-N., J.P., P.E., J.B.); StoP-AD Centre (P.-F.M., J.T.-M., M.-E.L.-M., P.R.-N., J.P., P.E., J.B.), Douglas Mental Health University Institute Research Centre, Montréal, Canada; and John Hopkins University (J.L.), Baltimore, MD.
Pedro Rosa-NetoFrom the McGill Centre for Integrative Neuroscience, Montreal Neurological Institute (C.M.), and McGill University Research Centre for Studies in Aging (M.S., P.R.-N.), McGill University (P.-F.M., M.-E.L.-M., P.R.-N., J.P., P.E., J.B.); StoP-AD Centre (P.-F.M., J.T.-M., M.-E.L.-M., P.R.-N., J.P., P.E., J.B.), Douglas Mental Health University Institute Research Centre, Montréal, Canada; and John Hopkins University (J.L.), Baltimore, MD.ORCID 0000-0001-9116-1376
Judes PoirierFrom the McGill Centre for Integrative Neuroscience, Montreal Neurological Institute (C.M.), and McGill University Research Centre for Studies in Aging (M.S., P.R.-N.), McGill University (P.-F.M., M.-E.L.-M., P.R.-N., J.P., P.E., J.B.); StoP-AD Centre (P.-F.M., J.T.-M., M.-E.L.-M., P.R.-N., J.P., P.E., J.B.), Douglas Mental Health University Institute Research Centre, Montréal, Canada; and John Hopkins University (J.L.), Baltimore, MD.
Pierre EtienneFrom the McGill Centre for Integrative Neuroscience, Montreal Neurological Institute (C.M.), and McGill University Research Centre for Studies in Aging (M.S., P.R.-N.), McGill University (P.-F.M., M.-E.L.-M., P.R.-N., J.P., P.E., J.B.); StoP-AD Centre (P.-F.M., J.T.-M., M.-E.L.-M., P.R.-N., J.P., P.E., J.B.), Douglas Mental Health University Institute Research Centre, Montréal, Canada; and John Hopkins University (J.L.), Baltimore, MD.
John BreitnerFrom the McGill Centre for Integrative Neuroscience, Montreal Neurological Institute (C.M.), and McGill University Research Centre for Studies in Aging (M.S., P.R.-N.), McGill University (P.-F.M., M.-E.L.-M., P.R.-N., J.P., P.E., J.B.); StoP-AD Centre (P.-F.M., J.T.-M., M.-E.L.-M., P.R.-N., J.P., P.E., J.B.), Douglas Mental Health University Institute Research Centre, Montréal, Canada; and John Hopkins University (J.L.), Baltimore, MD. john.breitner@mcgill.ca.
PREVENT-AD Research Group
Montreal Neurological Institute and Hospital · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo evaluate the safety and efficacy of low-dose naproxen for prevention of progression in presymptomatic Alzheimer disease (AD) among cognitively intact persons at risk.

methodsInvestigation of Naproxen Treatment Effects in Pre-symptomatic Alzheimer's Disease (INTREPAD), a 2-year double-masked pharmaco-prevention trial, enrolled 195 AD family history-positive elderly (mean age 63 years) participants screened carefully to exclude cognitive disorder (NCT-02702817). These were randomized 1:1 to naproxen sodium 220 mg twice daily or placebo. Multimodal imaging, neurosensory, cognitive, and (in ∼50%) CSF biomarker evaluations were performed at baseline, 3, 12, and 24 months. A modified intent-to-treat analysis considered 160 participants who remained on-treatment through their first follow-up examination. The primary outcome was rate of change in a multimodal composite presymptomatic Alzheimer Progression Score (APS).

resultsNaproxen-treated individuals showed a clear excess of adverse events. Among treatment groups combined, the APS increased by 0.102 points/year (SE 0.014;

conclusionsIn cognitively intact individuals at risk, sustained treatment with naproxen sodium 220 mg twice daily increases frequency of adverse health effects but does not reduce apparent progression of presymptomatic AD. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that, for people who are cognitively intact, low-dose naproxen does not significantly reduce progression of a composite indicator of presymptomatic AD.

Indexed as

AgedAlzheimer DiseaseAnti-Inflammatory Agents, Non-SteroidalDisease ProgressionDouble-Blind MethodFemaleHumansMaleMiddle AgedNaproxenProdromal SymptomsTreatment OutcomeAnti-Inflammatory Agents, Non-SteroidalNaproxen

Identifiers

PMID30952794
PMCPMC6512884
OpenAlexW2928086185

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.