Trial reportNeurology2019
INTREPAD: A randomized trial of naproxen to slow progress of presymptomatic Alzheimer disease.
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.
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.
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.
Who cites it
66 citing papers in PubMed, 112 citations in OpenAlex.
- Inhibition of p38α MAPK increases short-term astrocyte reactivity: the exploratory VIP trial in early Alzheimer's disease.Journal of neuroinflammation · 2025Trial
- Association of Proton Pump Inhibitor Use With Incident Dementia and Cognitive Decline in Older Adults: A Prospective Cohort Study.Gastroenterology · 2023Trial
- Randomized placebo-controlled trial of the effects of aspirin on dementia and cognitive decline.Neurology · 2020Trial
- No apparent effect of naproxen on CSF markers of innate immune activation.Annals of clinical and translational neurology · 2019Trial
- Longitudinal effects of cerebrovascular reactivity and cerebral pulsatility in cognitively intact older adults with APOE4: links with cognition.GeroScience · 2026Article
- Microglial checkpoint collapse in Alzheimer's disease: a tri-axial framework for biomarker-informed neuroimmune therapy.Journal of neuroinflammation · 2026Review
- NSAID use is associated with lower dementia and Alzheimer's disease prevalence and slower cognitive decline: A retrospective longitudinal analysis of the NACC cohort.medRxiv : the preprint server for health sciences · 2026Article
- Review
- Current progress in pathway-targeted therapeutics for Alzheimer's disease: mechanistic insights and windows of opportunity.Molecular and cellular biochemistry · 2026Review
- Anti-inflammatory and immunomodulatory therapies are associated with reduced risk of age-associated neurodegenerative diseases: impact of sex and treatment duration.Frontiers in aging neuroscience · 2026Article
- Calcium signaling hypothesis: A non-negligible pathogenesis in Alzheimer's disease.Journal of advanced research · 2025Review
- 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 · 2025Article
- Neuroinflammation in Alzheimer disease.Nature reviews. Immunology · 2025Review
- Immune modulation to treat Alzheimer's disease.Molecular neurodegeneration · 2025Review
- 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 · 2025Article
- Excessive Alcohol Use as a Risk Factor for Alzheimer's Disease: Epidemiological and Preclinical Evidence.Advances in experimental medicine and biology · 2025Review
- Sentinels of neuroinflammation: the crucial role of myeloid cells in the pathogenesis of gliomas and neurodegenerative diseases.Journal of neuroinflammation · 2024Review
- Differential effect of an evolving amyloid and tau pathology on brain phospholipids and bioactive lipid mediators in rat models of Alzheimer-like pathology.Journal of neuroinflammation · 2024Article
- Severe infections as a gateway to dementia.Nature aging · 2024Article
- Natural Compounds Oridonin and Shikonin Exhibit Potentially Beneficial Regulatory Effects on Select Functions of Microglia.Brain sciences · 2024Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
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- Commented on by
- Erratum issued
Authors and funding
11 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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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.