Objectives: To systematically review and synthesize the evidence on differential associations between antihypertensive medication (AHM) classes and the risk of incident dementia. Design: Systematic review and random effects frequentist network meta-analysis. Embase, MEDLINE, and the Cochrane library were searched from origin to December 2019. Setting and participants: Randomized controlled trials (RCTs) and prospective cohort studies that compared associations of different AHM classes with incident all-cause dementia and/or Alzheimer's disease over at least 1 year of follow-up. Measures: All cause dementia and/or Alzheimer's disease. Results: Fifteen observational studies and 7 RCTs were included. Data on AHM classes were available for 649,790 participants and dementia occurred in 19,600 (3.02%). Network meta-analysis showed that in observational studies, treatment with either calcium channel blockers (CCBs) or angiotensin II receptor blockers (ARBs) was associated with lower dementia risks than treatment with other antihypertensives: CCBs vs angiotensin converting enzyme inhibitors (ACE inhibitors) (HR¼0.84, 95% CI 0.74-0.95), beta blockers (HR¼0.83, 95% CI 0.73-0.95) and diuretics (HR¼0.89, 95% CI 0.78-1.01) and ARBs vs ACE inhibitors (HR¼0.88, 95% CI 0.81-0.97), beta blockers (HR¼0.87, 95% CI 0.77-0.99), and diuretics (HR¼0.93, 95% CI 0.83-1.05). There were insufficient RCTs to create a robust network based on randomized data alone. Conclusions and Implications: Recommending CCBs or ARBs as preferred first-line antihypertensive treatment may significantly reduce the risk of dementia. If corroborated in a randomized setting, these findings reflect a low-cost and scalable opportunity to reduce dementia incidence worldwide.

No abstract

Background Hypertension is an important risk factor for dementia. Specific antihypertensive medication (AHM) classes may lower dementia risk more effectively than others. We aim to systematically review and synthesize the evidence on differential associations between AHM classes and the risk of dementia, using network meta‐analysis. Method Embase, MEDLINE and the Cochrane library were searched from origin to December 2019. We included randomized controlled trials and prospective cohort studies, including non‐demented participants with ≥one year of follow‐up. Data were extracted following PRISMA guidelines. Data on individual AHM classes were pooled using random effects frequentist network meta‐analysis. Result Fifteen observational studies and seven RCTs were included. Dementia occurred in 19,600/649,790 (3.02%) individuals. In observational studies, treatment with calcium channel blockers (CCBs) and angiotensin II receptor blockers (ARBs) conveyed lower dementia risks than treatment with other antihypertensives: CCBs compared to ACE‐inhibitors (HR=0.84, 95%CI 0.74‐0.95), beta blockers (BB) (HR=0.83, 95%CI 0.73‐0.95) and diuretics (HR=0.89, 95%CI 0.78‐1.01); ARBs compared to ACE‐inhibitors (HR=0.88, 95%CI 0.81‐0.97), BB (HR=0.87, 95%CI 0.77‐0.99) and diuretics (HR=0.93, 95%CI 0.83‐1.05). There were too few RCTs to create a robust network based on randomized data but similar conclusions were suggested. Conclusion Recommending CCBs or ARBs as preferred first‐line antihypertensive treatment may significantly reduce the risk of dementia. If confirmed in randomized trials, these findings reflect a low‐cost and scalable opportunity to reduce dementia incidence world‐wide.