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INTREPAD: A randomized trial of naproxen to slow progress of presymptomatic Alzheimer disease
Meyer PF, Tremblay-Mercier J, Leoutsakos J, Madjar C, Lafaille-Magnan ME, Savard M, Rosa-Neto P, Poirier J et al.. Neurology, 2019-04-05
Topic: Amyloid, tau and blood-test diagnosis
Objective To evaluate the safety and efficacy of low-dose naproxen for prevention of progression in presymptomatic Alzheimer disease (AD) among cognitively intact persons at risk. Methods Investigation 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). Results Naproxen-treated individuals showed a clear excess of adverse events. Among treatment groups combined, the APS increased by 0.102 points/year (SE 0.014; p -12 ), but rate of change showed little difference by treatment assignment (0.019 points/year). The treatment-related rate ratio of 1.16 (95% confidence interval 0.64-1.96) suggested that naproxen does not reduce the rate of APS progression by more than 36%. Secondary analyses revealed no notable treatment effects on individual CSF, cognitive, or neurosensory biomarker indicators of progressive presymptomatic AD. Conclusions In 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.
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APA 7th
Meyer, P. F., Tremblay-Mercier, J., Leoutsakos, J., Madjar, C., Lafaille-Magnan, M. E., Savard, M., et al. (2019). INTREPAD: A randomized trial of naproxen to slow progress of presymptomatic Alzheimer disease. Neurology. https://doi.org/10.1212/wnl.0000000000007232
Vancouver
Meyer PF, Tremblay-Mercier J, Leoutsakos J, Madjar C, Lafaille-Magnan ME, Savard M, et al. INTREPAD: A randomized trial of naproxen to slow progress of presymptomatic Alzheimer disease. Neurology. 2019. doi:10.1212/wnl.0000000000007232. PMID: 30952794.
BibTeX
@article{meyer2019-30952794,
author = {Meyer, P. F. and Tremblay-Mercier, J. and Leoutsakos, J. and Madjar, C. and Lafaille-Magnan, M. E. and Savard, M. and Rosa-Neto, P. and Poirier, J. and others},
title = {{INTREPAD: A randomized trial of naproxen to slow progress of presymptomatic Alzheimer disease}},
journal = {Neurology},
year = {2019},
doi = {10.1212/wnl.0000000000007232},
pmid = {30952794},
url = {https://doi.org/10.1212/wnl.0000000000007232}
}
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Key findings
- Results Naproxen-treated individuals showed a clear excess of adverse events.
- The treatment-related rate ratio of 1.16 (95% confidence interval 0.64-1.96) suggested that naproxen does not reduce the rate of APS progression by more than 36%.
- Secondary analyses revealed no notable treatment effects on individual CSF, cognitive, or neurosensory biomarker indicators of progressive 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.
Why it matters
In this 2-year trial of 195 cognitively intact people at risk for Alzheimer disease, low-dose naproxen did not reduce the rate of progression on the Alzheimer Progression Score and showed no notable treatment effects on cerebrospinal fluid, cognitive, or neurosensory markers. Naproxen-treated individuals also had a clear excess of adverse events, so this provides evidence that naproxen does not slow presymptomatic Alzheimer disease.
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Study details
- Participants195
- Evidence strengthHigh
How this study scored 74/100
Published in a leading specialty journal, and it is a randomized controlled trial. Scored zero for effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomized controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 195 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 1 / 2 | Randomized (as stated in the record) |
| Times cited | 5 / 7 | Cited 114 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 12.7 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 4 / 6 | Cited 13.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 9 other studies in this library |
| Still being cited | 2 / 4 | Cited 25 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author John C.S. Breitner: h-index 93 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Johns Hopkins University: institution h-index 2,306 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30952794) |
| Free to read | 2 / 2 | Free to read |
| Total | 74 / 100 | — |
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