Journal article
Association of Terazosin, Doxazosin, or Alfuzosin Use and Risk of Dementia With Lewy Bodies in Men
Neurology, Vol.103(2), e209570
07/23/2024
DOI: 10.1212/WNL.0000000000209570
PMCID: PMC11226317
PMID: 38896813
Abstract
Background and objectives: Terazosin, doxazosin, and alfuzosin (Tz/Dz/Az) are α-1 adrenergic receptor antagonists that also bind to and activate a key adenosine triphosphate (ATP)-producing enzyme in glycolysis. It is hypothesized that the increase in energy availability in the brain may slow or prevent neurodegeneration, potentially by reducing the accumulation of alpha-synuclein. Recent work has suggested a potentially neuroprotective effect of the use of Tz/Dz/Az in Parkinson disease in both animal and human studies. We investigated the neuroprotective effects of Tz/Dz/Az in a closely related disease, dementia with Lewy bodies (DLB).
Methods: We used a new-user active comparator design in the Merative Marketscan database to identify men with no history of DLB who were newly started on Tz/Dz/Az or 2 comparator medications. Our comparator medications were other drugs commonly used to treat benign prostatic hyperplasia that do not increase ATP: the α-1 adrenergic receptor antagonist tamsulosin or 5α-reductase inhibitor (5ARI). We matched the cohorts on propensity scores and duration of follow-up. We followed up the matched cohorts forward to estimate the hazard of developing DLB using Cox proportional hazards regression.
Results: Men who were newly started on Tz/Dz/Az had a lower hazard of developing DLB than matched men taking tamsulosin (n = 242,716, 728,256 person-years, hazard ratio [HR] 0.60, 95% CI 0.50-0.71) or 5ARI (n = 130,872, 399,316 person-years, HR 0.73, 95% CI 0.57-0.93). while the hazard in men taking tamsulosin was similar to that of men taking 5ARI (n = 159,596, 482,280 person-years, HR 1.17, 95% CI 0.96-1.42). These results were robust to several sensitivity analyses.
Discussion: We find an association in men who are taking Tz/Dz/Az and a lower hazard of DLB compared with similar men taking other medications. When combined with the literature of Tz/Dz/Az on Parkinson disease, our findings suggest that glycolysis-enhancing drugs may be broadly protective in neurodegenerative synucleinopathies. A future randomized trial is required to assess these associations for causality.
Classification of evidence: This study provides Class III evidence that Tz/Dz/Az use reduces the rate of developing DLB in adult men.
Details
- Title: Subtitle
- Association of Terazosin, Doxazosin, or Alfuzosin Use and Risk of Dementia With Lewy Bodies in Men
- Creators
- Alexander Hart - University of MichiganGeorgina Aldridge - University of IowaQiang Zhang - University of IowaNandakumar S. Narayanan - University of IowaJacob E. Simmering - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Neurology, Vol.103(2), e209570
- DOI
- 10.1212/WNL.0000000000209570
- PMID
- 38896813
- PMCID
- PMC11226317
- NLM abbreviation
- Neurology
- ISSN
- 0028-3878
- eISSN
- 1526-632X
- Language
- English
- Date published
- 07/23/2024
- Academic Unit
- Neurology; Pulmonary, Critical Care, and Occupational Medicine; Health Management and Policy; Iowa Neuroscience Institute; Internal Medicine
- Record Identifier
- 9984643659202771
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