Open access paper:Key Points
- Question What are the comparative neurocognitive effects of an angiotensin receptor blocker, candesartan, and an angiotensin-converting enzyme inhibitor, lisinopril, on adults with hypertension and executive mild cognitive impairment?
Findings In this randomized clinical trial of 176 adults with hypertension, 12-month treatment with candesartan was associated with improvement in executive function and episodic memory compared with lisinopril.
Meaning These findings suggest that among older adults with hypertension and mild cognitive impairment, treatment with candesartan provided better neurocognitive effects compared with lisinopril despite equivalent blood pressure levels.
Effects of Candesartan vs Lisinopril on Neurocognitive Function in Older Adults With Executive Mild Cognitive Impairment: A Randomized Clinical Trial
Ihab Hajjar, MD, MS; Maureen Okafor, MD, MPH; Darius McDaniel, MS; et al.
JAMA Network Open. 2020;3(8):e2012252.
DOI: 10.1001/jamanetworkopen.2020.12252
https://jamanetwork.com/journals/jamane ... le/2769104
See, in particular, the Discussion for more details on the proposed mechanism and suggested Limitations on our extrapolations from this study.Abstract
Importance Observational studies have suggested that angiotensin receptor blockers are associated with a unique cognitive protection. It is unclear if this is due to reduced blood pressure (BP) or angiotensin receptors type 1 blockade.
Objective To determine neurocognitive effects of candesartan vs lisinopril in older adults with mild cognitive impairment (MCI).
Design, Setting, and Participants This randomized clinical trial included participants aged 55 years or older with MCI and hypertension. Individuals were withdrawn from prior antihypertensive therapy and randomized in a 1 to 1 ratio to candesartan or lisinopril from June 2014 to December 2018. Participants underwent cognitive assessments at baseline and at 6 and 12 months. Brain magnetic resonance images were obtained at baseline and 12 months. This intent-to-treat study was double-blind and powered for a sample size accounting for 20% dropout. Data were analyzed from May to October 2019.
Interventions Escalating doses of oral candesartan (up to 32 mg) or lisinopril (up to 40 mg) once daily. Open-label antihypertensive drug treatments were added as needed to achieve BP less than 140/90 mm Hg.
Main Outcomes and Measures The primary outcome was executive function (measured using the Trail Making Test, Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research tool) and secondary outcomes were episodic memory (measured using the Hopkins Verbal Learning Test-Revised) and microvascular brain injury reflected by magnetic resonance images of white matter lesions.
Results Among 176 randomized participants (mean [SD] age, 66.0 [7.8] years; 101 [57.4%] women; 113 [64.2%] African American), 87 were assigned to candesartan and 89 were assigned to lisinopril. Among these, 141 participants completed the trial, including 77 in the candesartan group and 64 in the lisinopril group. Although the lisinopril vs candesartan groups achieved similar BP (12-month mean [SD] systolic BP: 130 [17] mm Hg vs 134 [20] mm Hg; P = .20; 12-month mean [SD] diastolic BP: 77 [10] mm Hg vs 78 [11] mm Hg; P = .52), candesartan was superior to lisinopril on the primary outcome of executive function measured by Trail Making Test Part B (effect size [ES] = −12.8 [95% CI, −22.5 to −3.1]) but not Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research score (ES = −0.03 [95% CI, −0.08 to 0.03]). Candesartan was also superior to lisinopril on the secondary outcome of Hopkins Verbal Learning Test-Revised delayed recall (ES = 0.4 [95% CI, 0.02 to 0.8]) and retention (ES = 5.1 [95% CI, 0.7 to 9.5]).
Conclusions and Relevance These findings suggest that in older adults with MCI, 1-year treatment with candesartan had superior neurocognitive outcomes compared with lisinopril. These effects are likely independent of the BP-lowering effect of candesartan.
