Background: Hypertension is a recognized risk factor for dementia. However, evidence for using antihypertensive agents to reduce the risk of Alzheimer's disease in people with hypertension is inconclusive.
Objective: To examine the association between antihypertensive agents and the incidence of Alzheimer's disease in adults with hypertension and normal cognition.
Design: We conducted a systemic review and performed meta-analyses using Ovid MEDLINE, Ovid Embase, Ovid PsycINFO, Web of science and Scopus, from inception to 18th February 2022.
Setting: Cohort and case-control studies.
Participants: Adults ≥ 40 years with hypertension and normal cognition.
Intervention: Antihypertensive agents.
Measurements: We performed two separate meta-analyses, pooling the adjusted relative risk (RR) of non-antihypertensive comparator and antihypertensive comparator study design.
Results: We included nine studies, totalling 1,527,410 individuals. Meta-analysis of non-antihypertensive user comparator studies found that the use of antihypertensive agents is associated with a reduced risk of incident Alzheimer's disease (RR= 0.94, 95% CI 0.90-0.99; p=0.01). Meta-analysis of antihypertensive comparator studies found evidence that angiotensin II receptor blocker users are associated with a reduction in the risk of Alzheimer's disease compared to other antihypertensive agents (RR= 0.78, 95% CI 0.68-0.88; p< 0.001).
Conclusion: Our review provides evidence that the use of antihypertensive agents is associated with a lower incidence of Alzheimer's disease. The use of angiotensin II receptor blockers may provide the most benefit among antihypertensive agents. Lowering raised blood pressure may not be the only mechanism for cognitive protection and further investigation of the effects of angiotensin II on cognition is indicated.
Keywords: Alzheimer Disease; angiotensin receptor antagonists; angiotensin-converting enzyme inhibitors; antihypertensive agents; hypertension.