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Randomized trials

Does a blood-pressure pill slow Alzheimer decline?

Lawlor B, Segurado R, Kennelly S, et al. · PLoS medicine · 2018

Open access · cc by · source: Europe PMC

In 511 people with mild-to-moderate Alzheimer disease, 8 mg nilvadipine daily for 78 weeks was safe but no better than placebo on ADAS-Cog 12 (p=0.465).

Study at a glance

Design
RCT — Phase III investigator-led double-blind RCT of 8 mg sustained-release nilvadipine vs placebo for 78 weeks across 23 European centres (NILVAD)
N
N=511 · 577 screened; 511 randomised (258 placebo, 253 nilvadipine); mITT n=498
Population
Adults >50 years with mild-to-moderate probable Alzheimer disease (NINCDS-ADRDA; SMMSE 12–26) at 23 academic centres in nine European countries
Outcome
ADAS-Cog 12 progression (primary); gated CDR-sb; function, safety

Structured fields used in claim comparison tables when every cited study has a complete layer.

Key findings

No treatment benefit on the co-primary (p=0.465). 78-week ADAS-Cog 12 decline was 9.63 on placebo vs 9.41 on nilvadipine. Secondary CDR-sb and Disability Assessment for Dementia were also null. Deaths were similar (3 vs 4); AEs (1,129 vs 1,030) and SAEs (146 vs 101) were higher on nilvadipine.

Methodology

Randomised 511 eligible participants (258 placebo, 253 nilvadipine) at 23 centres in nine countries to once-daily 8 mg sustained-release nilvadipine or matched placebo for 78 weeks, with ADAS-Cog 12 as the primary outcome in a 498-person mITT set.

Limitations

The trial cannot rule out benefit at a pre-dementia stage; diagnosis lacked amyloid biomarkers, so some non-Alzheimer dementia was likely included.

How this study connects

Role on claims

Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.

  • Nilvadipine did not slow mild-to-moderate Alzheimer disease over 78 weeks.

    In 511 people with mild-to-moderate AD, 8 mg nilvadipine daily for 78 weeks was no better than placebo on ADAS-Cog 12 (p=0.465; 9.41 vs 9.63 point decline). CDR-sb and disability scores were also null; adverse events were more common on drug.

    Evidence for the claim as stated.

  • Taiwan claims link gabapentin/pregabalin use to higher later dementia rates, especially under age 50.

    Among 206,802 matched Taiwanese adults, gabapentin or pregabalin use associated with dementia incidence 980 vs 605 per 100,000 person-years (aHR 1.45), aHR 3.16 under age 50, and a cumulative-dose gradient.

    Scope note — randomized AD treatment null result ≠ observational gabapentinoid exposure risk

    Limits the claim's scope: a different population, assay, or outcome.

  • PET-confirmed p-tau217 accuracy, a null nilvadipine AD RCT, and gabapentinoid dementia incidence answer different questions. A high diagnostic AUC does not imply a drug will slow ADAS-Cog, and claims associations are not trial evidence.

    Evidence for the claim as stated.

Open questions

Tensions this paper is part of

From concept pages' “where studies disagree.” Disagreement means the same question; scope means different assays, populations, or outcomes.

History

When this study was placed

Dated entries from the concept change log — when this paper was added or removed as support, challenge, or qualifier on a claim.

  1. 2026-09-17

    Placed as supporting evidence on Alzheimer’s and MCI markers

    In 511 people with mild-to-moderate AD, 8 mg nilvadipine daily for 78 weeks was no better than placebo on ADAS-Cog 12 (p=0.465; 9.41 vs 9.63 point decline). CDR-sb and disability scores were also null; adverse events were more common on drug.

  2. 2026-09-17

    Placed as a scope qualifier on Alzheimer’s and MCI markers

    Among 206,802 matched Taiwanese adults, gabapentin or pregabalin use associated with dementia incidence 980 vs 605 per 100,000 person-years (aHR 1.45), aHR 3.16 under age 50, and a cumulative-dose gradient.

  3. 2026-09-17

    Placed as supporting evidence on Alzheimer’s and MCI markers

    PET-confirmed p-tau217 accuracy, a null nilvadipine AD RCT, and gabapentinoid dementia incidence answer different questions. A high diagnostic AUC does not imply a drug will slow ADAS-Cog, and claims associations are not trial evidence.

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