Alpha-blockers hold therapeutic potential against dementia with Lewy bodies

The use of the alpha-1 adrenergic receptor antagonists (alpha-blockers) terazosin, doxazosin, and alfuzosin—medications for benign prostate hyperplasia (BPH)—may help reduce the incidence of dementia with Lewy bodies (DLB) in men, as suggested in a study.

Propensity-score matched analyses of large data involving men with no history of DLB who initiated one of six drugs used to treat BPH showed that those taking alpha-blockers had a reduced risk of DLB compared with those taking tamsulosin (n=242,716, 728,256 person-years of follow-up; hazard ratio [HR], 0.60, 95 percent confidence interval [CI], 0.50–0.71) or 5α-reductase inhibitors (5ARIs [finasteride and dutasteride]; n=130,872, 399,316 person-years of follow-up, HR, 0.73, 95 percent CI, 0.57–0.93). [Neurology 2024;doi:10.1212/WNL.0000000000209570]

Meanwhile, the risk of DLB did not differ between the tamsulosin and 5ARI groups (HR, 1.17, 95 percent CI, 0.96–1.42). These results were robust to several sensitivity analyses.

Alpha-blockers can increase energy production in brain cells, an unexpected side effect that is absent in other BPH medications. This suggests a potential mechanism for the observed association between alpha-blockers use and a reduced risk of neurodegenerative diseases like Parkinson's disease and DLB, as the investigators pointed out.

It is a boon, given that “diseases like DLB or Parkinson’s disease, or Alzheimer’s disease are debilitating, and we don’t really have any good treatments that can modify the disease progression. We can treat symptoms, but we can’t actually slow the disease,” said lead study author Dr Jacob Simmering from the University of Iowa in Iowa City, Iowa, US.

“If terazosin and these similar medications can help slow this progression—if not outright preventing the disease—this would be important to preserving cognitive function and quality of life in people with DLB,” Simmering added.

One of the limitations of the study was its observational nature, with the results showing only an association between taking the alpha-blocker drugs and a reduced risk of DLB rather than a causal relationship, according to Simmering. Moreover, the study only included men considering the drugs’ indication, so it is unclear whether the findings would apply to women.

Nevertheless, Simmering and colleagues see great promise in terazosin, doxazosin, and alfuzosin due to their existing FDA approval, affordability, and long history of safe use.

“One of the most exciting things about this study is that we find that same neuroprotective effect that we saw in Parkinson's disease. If there is a broadly protective mechanism, these medications could potentially be used to manage or prevent other neurodegenerative diseases,” Simmering said.