Viagra for BRAIN Health?

By Dale Bredesen, M.D., Chief Science Officer for Apollo Health

A great deal of media attention was garnered by a recent study reporting that the use of sildenafil (Viagra) was associated with a reduction in risk for Alzheimer’s disease. The study was an elegant combination of informatics, epidemiology, and cell biology. Networks of genes and proteins associated with the two hallmarks of Alzheimer’s — beta-amyloid and tau — were evaluated in an effort to identify drugs that impact both, with the hypothesis that these may represent excellent candidates for treating Alzheimer’s.

Four candidates were identified: one, sildenafil, turned out to be associated with reduced risk for Alzheimer’s disease (about 70% reduction in men and 30% in women), when insurance records were analyzed. Unfortunately, another one, lansoprazole (a proton pump inhibitor used for GERD, or gastroesophageal reflux), is associated with increased risk for Alzheimer’s. The other two — dantrolene (which prevents calcium release inside muscle cells) and deferoxamine (which binds iron) — had too little data to determine whether or not their use may be associated with any alteration of risk for Alzheimer’s.

So of the four drugs identified, one good, one bad, and two unknown — sounds almost random, but hey, anything that may be helpful is greatly appreciated. The researchers went on to show that sildenafil, when applied to neurons or microglia (immune cells from brain) that had been generated from Alzheimer stem cells, increased neuronal process growth and reduced the phospho-tau that is found in the tangles in Alzheimer’s. This sounds promising.

The big questions now are: first, does sildenafil actually cause the reduced risk, or is this simply a non-causal association? For example, it is well documented that the brain changes of Alzheimer’s begin about two decades before a diagnosis, so perhaps the people who had pre-Alzheimer’s, before diagnosis, had less interest in using sildenafil. Or perhaps those interested in using sildenafil had better hormone levels and social connections, and thus better brain support?

Second, the study only addressed risk, not treatment — it is a big leap from risk reduction to reversal of cognitive decline. In fact, the only sustained reversals of cognitive decline in patients with Alzheimer’s or pre-Alzheimer’s have been with patients on the ReCODE protocol. So will sildenafil prove to be effective? Upcoming clinical trials should answer that critical question.