There is evidence that hypertension in midlife can increase the risk of Alzheimer's disease and vascular dementia in late life. In addition, some treatments for hypertension have been proposed to have cognitive benefits, independent of their effect on hypertension. Consequently, there is potential to repurpose treatments for hypertension for dementia. This study systematically assessed ten antihypertensive drug classes for this purpose, using data on over 940,000 patients from the UK Clinical Practice Research Datalink.

Treatments for hypertension were assessed in an instrumental variable (IV) analysis to address potential confounding by indication. Physicians’ prescribing preference was used as a categorical instrument, defined by the physicians’ last seven prescriptions, and the analysis was adjusted for prescription year. A multivariable logistic regression analysis was also conducted to compare biases. Beta-adrenoceptor blockers were used as the control drug throughout.

Treatments for hypertension had little effect reducing the risk of Alzheimer's disease, vascular dementia, and other dementias. These results differ from existing studies considering specific antihypertensive drug classes. For example, we estimated angiotensin converting enzyme inhibitors to result in 2.2 per 1000 (95% CI 8.1–3.6) fewer cases of Alzheimer's disease among those treated–a much smaller reduction than previously reported. Comparison of our IV and logistic regression analyses suggests that this is likely due to confounding in non-IV studies.

This study is the first to systematically assess all the major antihypertensive drug classes. The contradiction with previous studies suggests that continued research into the repurposing of these treatments for dementia is required. It also highlights the need for further research into the biological mechanisms that link hypertension and dementia so that we can better understand the confounding in such analyses.