Phosphodiesterase‑5 inhibitors and Alzheimer’s disease; a meta‑analysis on clinical studies

Q: What are the key findings of this study?

Phosphodiesterase-5 inhibitor administration is associated with a significantly reduced risk of Alzheimer's disease incidence compared to no drug use (HR 0.47).

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Alzheimer's disease (n=4833558). Intervention: Phosphodiesterase-5 inhibitors (PDE5Is) vs. No drug use. Primary outcome: Alzheimer's disease incidence (HR 0.47, 95% CI 0.26-0.82, p=0.01).

Saman Behboodi Tanourlouee; Parham Torabinavid; Ali Vaezi; Mina Ghorbanpour; Mir Saeed Yekaninejad; Erfan Amini; Masoud Bitaraf

doi:10.1038/s44400-025-00005-3

April 7, 2025npj DementiaOpen Access

Phosphodiesterase‑5 inhibitors and Alzheimer’s disease; a meta‑analysis on clinical studies

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Key result

PDE5 inhibitors linked to ~53% lower Alzheimer's disease risk versus no use.

HR 0.47
95% CI 0.26-0.82
P=0.01
n=4,833,558

Why the study?

To evaluate the potential therapeutic benefits of phosphodiesterase-5 inhibitors on Alzheimer's disease.

Does phosphodiesterase-5 inhibitors administration reduce the risk of Alzheimer's disease in adults?

Study Design

Type

Meta-Analysis (n=4,833,558)

Structured PICO

Does phosphodiesterase-5 inhibitors administration reduce the risk of Alzheimer's disease in adults?

P

Population

4,833,558 individuals from 7 observational studies evaluating the association between phosphodiesterase-5 inhibitor use and the incidence of Alzheimer's disease.

E

Exposure

Phosphodiesterase-5 inhibitors (PDE5Is) including sildenafil, tadalafil, vardenafil, and avanafil, indicated for erectile dysfunction, benign prostatic hyperplasia, or pulmonary hypertension.

C

Comparator

No drug use, non-PDE5I users, or users of comparator drugs not in trial for Alzheimer's disease (e.g., diltiazem, glimepiride, furosemide, nifedipine, endothelin receptor antagonists).

O

Outcome

Alzheimer's disease (AD) incidence

Main Result

Hazard Ratio: 0.47 (95% CI 0.26–0.82)

p-value: p=0.01

Limitations

Observational design of included studies introduces the possibility of residual confounding.
Reliance on data from insurance databases in the USA and UK limits generalizability to other regions with differing healthcare infrastructures.
Substantial variances between groups at the onset of the cohort studies, follow-up durations, daily dosage, and duration of consumption.
Inadequate details regarding loss-to-follow-up in the included studies.
Observational design of included studies with baseline differences and potential residual confounding
Reliance on data from insurance databases in the USA and UK limits generalizability to other regions
Variability in comparator groups contributes to heterogeneity in pooled estimates
Differences in follow-up periods and lack of clear explanation for loss to follow-up
Different indications for drug intake resulted in varying numbers of male and female participants

Implication

The administration of phosphodiesterase-5 inhibitors is associated with a significantly reduced risk of Alzheimer's disease, providing a foundation for future phase 3 randomized controlled trials.

Abstract

To evaluate the potential therapeutic benefits of phosphodiesterase-5 inhibitors (PDE5Is) on Alzheimer’s disease (AD), electronic databases Embase, Scopus, and Medline were systematically searched from inception to March 18th, 2024. Studies assessing the association between the use of PDE5Is and AD incidence were included. Random-effects model of restricted maximum likelihood estimator was used to pool data. Seven studies were reviewed comprising 4,833,558 individuals, of which 348,546 received treatment with one of the PDE5Is. Pooled hazard ratios (HR) for AD incidence, comparing PDE5Is with no drug use (HR = 0.47, 95% CI 0.26–0.82, p -value: 0.01), and PDE5Is with no drug or drugs not in trial for AD (HR = 0.41, 95% CI 0.33–0.52, p -value: <0.01) were calculated. Synthesized evidence indicates PDE5Is administration is associated with AD risk reduction, supporting conduct of phase 3 clinical trials.

Discussion

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Cite This Study

Tanourlouee et al. (2025) conducted a meta-analysis in Alzheimer's disease (n=4,833,558). Phosphodiesterase-5 inhibitors (PDE5Is) vs. No drug use was evaluated on Alzheimer's disease incidence (HR 0.47, 95% CI 0.26-0.82, p=0.01). Phosphodiesterase-5 inhibitor administration is associated with a significantly reduced risk of Alzheimer's disease incidence compared to no drug use (HR 0.47).

synapsesocial.com/papers/6a2074b3d48e67d1607803c5 https://doi.org/10.1038/s44400-025-00005-3

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Phosphodiesterase‑5 inhibitors and Alzheimer’s disease; a meta‑analysis on clinical studies

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Phosphodiesterase‑5 inhibitors and Alzheimer’s disease; a meta‑analysis on clinical studies

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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