Phosphodiesterase-5 Inhibition and Alzheimer’s Disease Risk: A Mendelian Randomisation Study 2025: “No evidence of a causal association between PDE5 inhibition and AD risk was found in the main analyses. Similar findings were obtained in the sex-stratified analysis. Our study uses genetic data to triangulate the evidence and suggests that PDE5 inhibitors are unlikely to decrease the risk of AD.”
So PDE5i probably useless for AD but not harmful (second paper seems better). For LBD: TBD.
Regular use of PDE5 inhibitors is associated with an overall 1.85-fold increased risk for a composite of ocular adverse events, specifically increasing the incidence rate of serous retinal detachment by 2.58 times, ischemic optic neuropathy by 2.02 times, and retinal vascular occlusion by 1.44 times.
I’m starting to lose a little bit of faith in PDE5’s. I still think there is benefit overall, but this is one of those rare drugs that causes annoying side effects for me (bloodshot eyes, acid reflux, and nasal congestion).
It’s due to Fig. 2 being unclear. The dot that matters is the one in the middle not the last one. But then the result for vascular dementia is not clear either. I asked on X, maybe if people like he’ll be more likely to see who knows: https://x.com/ADssx/status/2061609418773373071
5mg gives me all of those side effects. Dropped to 2.5mg and it was better but still enough to give me milder side effects. I will still take it on demand when necessary though.
Those numbers can certainly sound a bit scary, but what are the baseline risks?
If I (hypothetically) can trade off a 2.02 increase in ischemic optic neuropathy for a 2.02 decrease in heart attacks, that’s probably a good trade-off overall, since heart attacks are much more common.
So I don’t really like the focus on only odds ratios unless we can also think about the baseline incidence. (And ideally, we all individualise those for ourselves. Somebody with overt CVD like a positive calcium score might weigh cardioprotection more heavily.)
I fit right in this demographic. At 81, CAC = ~400, 5mg tadalafil qd, I’ve recently developed a ‘macular pucker’ ( epiretinal membrane ) in one eye. Related to tadalafil use? No idea; OD said it’s not uncommon for ‘the elderly’ = me. Probably stay consistant with @relaxedmeatball’s logic and ‘stand pat’ with tadalafil use.
I’m actually pretty simplistic about why I take tadalafil every day. My basic logic is that vasodilation is good for longevity. Same reason I really like being in the sun, because it triggers release of nitric oxide and vasodilation. Also, as a 60 year old, I find it helps keep tone in my nether regions for urination and erections.