RapAdmin, For anyone with a doctor’s prescription not covered by insurance in the USA, Amazon Pharmacy provides a 90-day supply of 5 mg generic tadalafil for $32.00. You have to be an Amazon Prime member for this. I believe the generic version is made in India.
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Another PDE5 inhibitor paper, albeit an APP mouse model.
Phosphodiesterase 5 inhibitor mirodenafl ameliorates Alzheimer-like pathology and symptoms by multimodal actions
Conclusions: These fndings strongly suggest that the PDE5 inhibitor mirodenafl shows promise as a potential polypharmacological drug candidate for AD treatment, acting on multiple key signaling pathways involved in amy‑loid deposition, phosphorylated tau burden, the cGMP/PKG/CREB pathway, GSK-3β kinase activity, GR signaling, and the Wnt/β-catenin signaling. Mirodenafl administration to the APP-C105 AD mouse model also improved cognitive behavior, demonstrating the potential of mirodenafl as a polypharmacological AD therapeutic agent.
cGMP was a pathway implicated in Sildenafil (Viagara).
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Interesting…looks like that particular med is only available in South Korea for now, but hopefully someone will next do a retrospective study looking at patients who have been on it to see if they’ve had less dementia than a comparable group.
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Effect of low-dose tadalafil once daily on glycemic control in patients with type 2 diabetes and erectile dysfunction.
Effective in improving glycemic control and erectile function in patients with type 2 diabetes and erectile dysfunction.
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Another approach to lowering risk of dementia:
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What the heck? Why would more than 10k be associated with greater risk of dementia? There must be some major confounding variables involved here.
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The brain seems especially sensitive to inflammation and ROS, both of which go up shortly after exercise initiating the hormesis response. The more of it the better for the cardiovascular system, but maybe the brain gets overwhelmed and our innate antioxidants can’t rescue it quickly end.
Everything is U shaped.
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Doing regular activities at home should bring one at roughly 8K-12K steps per day - and that is without any exercise. There are so many studies showing the benefits of exercise when it comes to brain aging and DNA damage. (Albeit indeed there are also some studies showing excessive exercise can induce DNA damage).
I don’t understand how all that research rhymes with these studies claiming more than 10K steps per day are associated with a greater risk of dementia. That can’t be right.
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I imagine the high step-count group has an overrepresentation of people with body-taxing manual labor jobs. That demographic associates with shorter life span.
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From @Agetron in another thread:
Results from the National Institutes of Health’s Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) study show that sildenafil (Viagra) and tadalafil (Cialis) may not be suitable candidates for treating dementia. These findings are contrary to similar, previously reported research from another group. In this new study, NIH researchers and collaborators used data from Medicare beneficiaries and determined the medications sildenafil and tadalafil do not reduce the risk of Alzheimer’s disease and related dementias. The study was funded by the NIH National Institute on Aging (NIA) and results published in Brain Communications . Identifying existing drugs that may also be repurposed for dementia could potentially get treatments to those in need faster than the traditional drug discovery process.
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I’ve been buying Sildenafil from Costco for years. Currently it costs $32.99 to fill 90 100mg tablets. I do have slight hearing loss - I have trouble hearing faint sounds in noisy environments. This could be due to the sildenafil.
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Party poopers. 
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Sam wrote: “I have trouble hearing faint sounds in noisy environments. This could be due to the sildenafil.”
Or getting older… 
Good news… Rapamycin helps reverse hearing loss. In the almost 2.5 years of my use hearing is fantastic.
My urologist says daily 2mg of tadalafil (same sildenafil) is healthy for your male bits!
I think user AmyK concurs…
I am not complaining.
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Anyone seen this study. Any others similar or contradictory?
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Hi Ben, welcome to the site. There has been a long discussion about that study. See the thread here: Rapamycin increases Alzheimer's-associated plaques in mice, study finds
Also - some other news related to rapamycin and alzheimers:
Here: Intranasal Rapamycin Lessens Alzheimer-like Cognitive Decline in a Mouse Model of Down Syndrome
Here: Fighting Alzheimer’s with Increased Autophagy via Rapamycin + Trehalose
Here: Rapamycin and Alzheimer’s disease: Time for a clinical trial? - PMC
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If you’re taking cialis, please be aware about interactions with antifungals.
I took a low dose (2.5 mg) years ago, then applied tolnaftate (tinactin) on a fungal infection. It produced a racing heartbeat. I was so scared, I almost went to the ER. Deep breathing and all that did not help. It did not help either, that tadalafil has a long half-life. So the whole day, I was in bed doing deep breathing. It stopped hours later, maybe at the half-life mark.
I learned, later, from a commercial, that that was one of the warnings. But it was for oral antifungals. This was merely topical.
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https://twitter.com/agingdoc1/status/1659778474553528321?s=20
Feasibility of high-dose tadalafil and effects on insulin resistance in well-controlled patients with type 2 diabetes (MAKROTAD): a single-centre, double-blind, randomised, placebo-controlled, cross-over phase 2 trial
Phosphodiesterase-5 inhibitors exert positive vascular and metabolic effects in type 2 diabetes (T2D), but the effect on insulin resistance in T2D is unclear.
https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00162-1/fulltext
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Tadalafil/sildenafil show promise when it comes to improvie the aging cardiovascular system. Besides targeting mTOR and glucosemetabolism I find it important to specifically target the cardiovascular system. A man is as old as his arteries and his capillaries.
Captoril show an interesting curve and it has a systemic vasodilatory effect. Captopril blocks the conversion of angiotensin I to angiotensin II and prevents the degradation of vasodilatory prostaglandins, thereby inhibiting vasoconstriction and promoting systemic vasodilation.
MPD: ITP survival analysis: captopril (jax.org)
And conceptual mice studies indicate a potential for radical lifeextension when targetting the vascular system. But it comes with the concern of increased risk for cancers. But mice, that usually die from different neoplasms - cancers, show radical life extension in the study below. It would be great to see what kind of effect rapamycin combined with captoril would have on the lifespan of mice.
VEGF to extend lifespan? (targeting vascular aging) - YouTube
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I have been using low-dose Tadalafil and nitric oxide capsules with the hope that they will improve my vascular system. The latter has definitely increased my CGM glucose measurements, presumably, because of the high vitamin C content.
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If you care to look on Google Scholar there are many articles that suggest exercise is a way to increase VEGF.
It’s amazing that mouse studies show increasing VEGF increases lifespan by an amazing 48%. I don’t why this has not received more attention.
Again exercise seems to be the first thing ahead of rapamycin or anything else in increasing human life span. By the way, even though I go to the gym and exercise a lot, I don’t find it particularly enjoyable while I am doing it, but I always feel better afterward.
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