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Phosphodiesterase Type 5 Inhibitors in Men With Erectile Dysfunction and the Risk of Alzheimer Disease: A Cohort Study
Adesuyan M, Jani YH, Alsugeir D, Howard R, Ju C, Wei L, Brauer R.. Neurology, 2024-02-07
Topic: Amyloid, tau and blood-test diagnosis
Background and objectives Repurposing phosphodiesterase type 5 inhibitors (PDE5Is) as drugs for Alzheimer disease (AD) risk reduction has shown promise based on animal studies. However, evidence in humans remains inconclusive. Therefore, we conducted a cohort study to evaluate the association between PDE5I initiation compared with nonuse and the risk of developing AD in men with erectile dysfunction (ED). Methods Using electronic health records from IQVIA Medical Research Data UK (formerly known as the THIN database), we identified men aged ≥40 years with a new diagnosis of ED between 2000 and 2017. Individuals with a previous diagnosis of dementia, cognitive impairment, confusion, or prescription for dementia symptoms were excluded. The occurrence of incident AD was identified using diagnostic read codes. To minimize immortal-time bias, PDE5I initiation was treated as a time-varying exposure variable. Potential confounders were adjusted using inverse probability of treatment weighting based on propensity scores. Cox proportional hazard models were used to estimate the adjusted hazard ratio (HR) with 95% CIs. A secondary analysis explored the association between AD and the cumulative number of PDE5I prescriptions. Sensitivity analyses included lag (delay) periods of 1 and 3 years after cohort entry to address the prodromal stage of AD. Results The study included 269,725 men, with 1,119 newly diagnosed with AD during a median follow-up of 5.1 (interquartile range 2.9-8.9) years. The adjusted HR in PDE5I initiators compared with nonuse was 0.82 (95% CI 0.72-0.93). The associated risk of AD decreased in individuals issued >20 prescriptions: HR 0.56 (95% CI 0.43-0.73) for 21-50 prescriptions and HR 0.65 (95% CI 0.49-0.87) for >50 prescriptions. Sensitivity analysis with a 1-year lag period supported the primary findings (HR 0.82, 95% CI 0.72-0.94), but the results differed with the inclusion of a 3-year lag period (HR 0.93, 95% CI 0.80-1.08). Discussion PDE5I initiation in men with ED was associated with a lower risk of AD, particularly in those most frequently issued prescriptions. The differences between primary and sensitivity analyses highlight the need to explore the optimal lag period. To enhance the generalizability of our findings, a randomized controlled trial including both sexes and exploring various PDE5I doses would be beneficial to confirm the association between PDE5I and AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Adesuyan, M., Jani, Y. H., Alsugeir, D., Howard, R., Ju, C., Wei, L., et al. (2024). Phosphodiesterase Type 5 Inhibitors in Men With Erectile Dysfunction and the Risk of Alzheimer Disease: A Cohort Study. Neurology. https://doi.org/10.1212/wnl.0000000000209131
Vancouver
Adesuyan M, Jani YH, Alsugeir D, Howard R, Ju C, Wei L, et al. Phosphodiesterase Type 5 Inhibitors in Men With Erectile Dysfunction and the Risk of Alzheimer Disease: A Cohort Study. Neurology. 2024. doi:10.1212/wnl.0000000000209131. PMID: 38324745.
BibTeX
@article{adesuyan2024-38324745,
author = {Adesuyan, M. and Jani, Y. H. and Alsugeir, D. and Howard, R. and Ju, C. and Wei, L. and Brauer, R.},
title = {{Phosphodiesterase Type 5 Inhibitors in Men With Erectile Dysfunction and the Risk of Alzheimer Disease: A Cohort Study}},
journal = {Neurology},
year = {2024},
doi = {10.1212/wnl.0000000000209131},
pmid = {38324745},
url = {https://doi.org/10.1212/wnl.0000000000209131}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Therefore, we conducted a cohort study to evaluate the association between PDE5I initiation compared with nonuse and the risk of developing AD in men with erectile dysfunction (ED).
- Results The study included 269,725 men, with 1,119 newly diagnosed with AD during a median follow-up of 5.1 (interquartile range 2.9-8.9) years.
- The adjusted HR in PDE5I initiators compared with nonuse was 0.82 (95% CI 0.72-0.93).
- Sensitivity analysis with a 1-year lag period supported the primary findings (HR 0.82, 95% CI 0.72-0.94), but the results differed with the inclusion of a 3-year lag period (HR 0.93, 95% CI 0.80-1.08).
- Discussion PDE5I initiation in men with ED was associated with a lower risk of AD, particularly in those most frequently issued prescriptions.
Why it matters
In this cohort of 269,725 men with erectile dysfunction, starting a phosphodiesterase type 5 inhibitor was associated with a lower risk of developing Alzheimer disease compared with nonuse, with an adjusted hazard ratio of 0.82. Because this is an observational cohort study rather than a randomized trial, it shows an association and cannot prove that these drugs prevent Alzheimer's disease.
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Study details
- Study designrandomized controlled trial
- Participants269,725
- Effect sizeHR 0.56 (95% CI 0.43-0.73); HR 0.65 (95% CI 0.49-0.87); HR 0.82
- Evidence strengthHigh
How this study scored 76/100
Published in a leading specialty journal, and it is a randomised controlled trial.
| 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 randomised 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 | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 4 / 4 | 269,725 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 3 / 7 | Cited 35 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.8 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 4 / 6 | Cited 9.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 35 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Ruth Brauer: h-index 25 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38324745) |
| Free to read | 2 / 2 | Free to read |
| Total | 76 / 100 | — |
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