Use of α1-adrenoceptor antagonists tamsulosin and alfuzosin and the risk of Alzheimer's disease

Purpose Tamsulosin has been associated with dementia, but the results have been inconsistent. Concerns have been raised about using exposure assessment time too close to the outcome. We investigated the association between use of alpha 1-adrenoceptor antagonists indicated for benign prostate hyperplasia and risk of Alzheimer's disease (AD) using different exposure windows. Methods The study (24 602 cases and 98 397 matched controls) included men from the Finnish nationwide nested case-control study on Medication and Alzheimer's disease (MEDALZ). Cases received clinically verified AD diagnosis during 2005-2011 and were community-dwelling at the time of diagnosis. Use of tamsulosin and alfuzosin in 1995-2011 was identified from the Prescription Register and categorized based on whether it had occurred within 3 years before AD diagnosis (lag time) or before that. Dose-response analysis using defined daily doses of drug (DDDs) was conducted. Associations were investigated with conditional logistic regression, adjusted for confounders and mediators. Results The use of alpha 1-adrenoceptor antagonists before lag time associated with an increased risk of AD (OR 1.24 [1.20-1.27]). After adjustment for comorbidities and concomitant drug use throughout the assessment time (confounders) and healthcare contacts within the lag period (mediators), the association weakened (aOR 1.10 [1.06-1.14]). We found no evidence of dose-response-relationship when comparing the users of higher than median DDDs to the users of lower than median DDDs. Conclusion Our findings, especially the lack of dose-response-relationship and attenuation after mediator adjustment, do not provide strong support for the previous hypothesis on alpha 1-adrenoceptor antagonists as a risk factor for dementia.

Automated summary

The study found an increased risk of AD associated with the use of alpha 1-adrenoceptor antagonists before the lag time, but the association weakened after adjustment for confounders and mediators. No dose-response relationship was found when comparing users of higher than median DDDs to users of lower than median DDDs. The findings do not provide strong support for the previous hypothesis on alpha 1-adrenoceptor antagonists as a risk factor for dementia.