Antihypertensive drug classes and incident dementia: Findings from the PreDIVA observational extension study.

Background: Midlife hypertension is a risk factor for all‐cause dementia. Treatment of hypertension with antihypertensive medication (AHM) may therefore be a promising strategy to delay or prevent dementia. Recent reports have suggested that AHM are associated with differential effects on dementia risk, due to class‐specific mechanisms. In this study, we assess the association between different AHM‐classes and incident dementia, using data from the preDIVA observational extension (POE) study. Method: All participants who reported use of AHM at baseline were included in the analyses. We distinguished angiotensin‐converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta‐blockers, calcium channel blockers (CCBs), and diuretics. Data on incident dementia was collected during the randomised phase at 2, 4, 6‐8 and, after discontinuation of the intervention, 10‐12 years after baseline. Cox proportional hazards regression was used to study the association between use of different AHM‐classes, compared with use of any other AHM class, and incident dementia. A post‐hoc analysis was performed, dividing follow‐up time in two periods (preDIVA median follow‐up acting as cut‐off point) to account for the effect of time between exposure and dementia. Result: 1953 participants who reported AHM use at baseline were included, with a mean age of 74.5 (±2.5) and a mean systolic blood pressure of 156.4 mmHg (±21.5). After a median follow‐up of 10.4 years (IQR 6.7‐11.0), 228 (11.7%) participants had developed dementia. Adjusted hazard ratios (HR) for dementia were 1.07 (95%CI 0.80‐1.42) for ACE inhibitors, 0.75 (95%CI 0.53‐1.06) for ARBs, 1.00 (95%CI 0.77‐1.31) for beta‐blockers, 0.92 (95%CI 0.68‐1.24) for CCBs, and 1.02 (95%CI 0.78‐1.33) for diuretics. ARBs and CCBs were inversely associated with dementia during the first time period (HR 0.46, 95%CI 0.25‐0.84 and HR 0.62, 95%CI 0.38‐0.99 respectively), which was not apparent anymore during the second one. Conclusion: Despite short‐term beneficial associations of CCBs and ARBs and a promising HR for ARBs also after longer follow‐up, associations between any AHM‐class and incident dementia were not convincing after complete follow‐up. These findings are possibly best explained by the long follow‐up in older participants with high mortality‐ and dementia rates, possibly attenuating AHM‐class effects on dementia incidence. [ABSTRACT FROM AUTHOR]