Drug repositioning for Alzheimer’s disease and related dementias: Network meta‐analysis using individual participant data

Abstract

AbstractBackgroundAlzheimer’s disease and related dementias (AD/ADRD) are chronic neurodegenerative pathology and bring a growing public health concern worldwide; particularly, treatments for AD/ADRD remain limited. Drug repositioning has alternate potential to provide an opportunity to accelerate newly identified treatments for individuals with AD/ADRD. Like, some studies have investigated effects of antihypertensive medications on dementia risk, but inconsistent results are reported. In this study, we aim to determine whether existing or approved drugs, including antihypertensive drugs and hormone replacement therapy, enable to reduce the risk of dementia or cognitive impairment.MethodWe searched PubMed, MEDLINE and EMBASE for published trials up to December 31, 2020. The primary outcome of interest was incident dementia or incident cognitive decline. We examined the following candidate repurposed drugs, including hormone replacement therapy and antihypertensive drug classes: diuretics, beta blockers (BB), angiotensin‐converting enzyme inhibitors (ACE‐I), angiotensin II receptor blockers (ARB), calcium channel blockers (CCB), alpha blockers, central agonists, vasodilators, and aldosterone blockers. We conducted a random‐effects network meta‐analysis using individual participant data to identify both direct and indirect evidence from the include trials.ResultFour trials, including 19,632 participants and 10 candidate repurposed drugs, met the eligibility criteria, as shown in Figure 1. The results of network meta‐analysis were presented as a league table in Figure 2. We found that aldosterone blockers (OR = 2.32; 95% CI: 1.41 to 3.81), ARB (OR = 1.31; 95% CI: 1.07 to 1.60) and hormone therapy (OR = 1.36; 95% CI: 1.08 to 1.71) were less effective in reducing dementia risk when compared with ACE‐I. Moreover, all the other drugs reduced dementia risk statistically significantly compared with aldosterone blockers (ORs ranging from 0.46 (95% CI: 0.27 to 0.79) for alpha blockers to 0.59 (95% CI: 0.35 to 0.99) for hormone replacement therapy).ConclusionOur findings showed some classes of antihypertensive drugs may have more potential to prevent the incidence of dementia or cognitive decline than the other classes. However, further research for validation of our results is needed.