TABLE 1.
Summary of research studies evaluating the effects of RAS-acting agents on cognition and dementia.
| Author/year | Study design | Number of patients | Mean age (years) | Follow-up (years) | Treatment | Disease | Results |
| Tzourio et al., 2003 | Double-blind RCT | 6,105 | 64 | 3.9 | ACEI | Dementia | Active treatment (perindopril with or without indapamide) was associated with reduced risk of dementia (relative risk reduction, 12% [95% CI, −8% to 28%]; P = 0.2). Cognitive decline was seen in 9.1% of the actively treated group and 11.0% of the placebo group (risk reduction, 19% [95% CI, 4% to 32%]; p = 0.01). |
| Ohrui et al., 2004a | Cohort study | 4,124 | 69 | 8 | ACEI | AD | Central-acting captopril and perindopril were associated with a significantly lower incidence of AD than the use of those that cannot inhibit brain ACE (imidapril or enalapril) (odds ratio = 0.25, 95% CI = 0.08–0.75; p = 0.014). |
| Ohrui et al., 2004b | RCT | 162 | 76 | 1 | ACEI | AD | The mean 1-year decline in MMSE scores in the participants of brain-penetrating ACEIs (perindopril or captopril) was lower than those in the participants of non-brain-penetrating ACEIs (imidapril or enalapril) and CCBs (p < 0.001). |
| Khachaturian et al., 2006 | Cohort study | 3,217 | 74.9 | 3 | ACEI | AD | In the analyses of AD risk among different types of antihypertensive medications, ACEIs (HR, 1.13; 95% CI, 0.60–1.98) and CCBs (HR, 0.86; 95% CI, 0.45–1.53) showed no impact on AD risk. |
| Li et al., 2010 | Prospective cohort analysis | 819,491 | 74 | 4 | ARB/ACEI | AD | A significant reduction in the occurrence of AD was identified with ARBs compared to lisinopril (HR 0.81, 95% CI 0.68–0.96, P = 0.016). |
| Yasar et al., 2013 | Post hoc analysis of RCT | 1,928 | 78.6 | 6.1 | ARB/ACEI | AD | HR for AD occurrence among participants with normal cognition was found 0.51 in diuretic (95% CI 0.31–0.82), 0.31 in ARB (95% CI 0.14–0.68), 0.50 in ACEI (95% CI 0.29–0.83), 0.62 in CCB (95% CI 0.35–1.09), and 0.58 in BB (95% CI 0.36–0.93) users. |
| Barthold et al., 2020 | Retrospective cohort study | 694,672 | 77.3 | 7 | ARB/ACEI | AD | The annual AD and related dementias incidence rate was found 2.07% among persons using a RAS-acting antihypertensive and any statin, and 2.64% among persons using a non-RAS-acting antihypertensive and any statin. ACEI + pravastatin OR = 0.942 (CI: 0.899–0.986, p = 0.011), ACEI + rosuvastatin OR = 0.841 (CI: 0.794–0.892, p < 0.001), ARB + pravastatin OR = 0.794 (CI: 0.748–0.843, p < 0.001), ARB + rosuvastatin OR = 0.818 (CI: 0.765–0.874, p < 0.001). |
ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CCB, calcium-canal blocker; BB, beta-blocker; AD, Alzheimer’s disease; RCT, randomized controlled trial; HR, hazard ratio; CI, confidence interval; OR, odds ratio.