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Effects of candesartan vs. lisinopril on neurocognitive functioning in executive mild cognitive impairment: The CALIBREX trial
Author(s) -
Hajjar Ihab,
Okafor Maureen O.,
McDaniel Darius,
Obideen Malik,
Dee Elizabeth,
Shokouhi Mahsa,
Quyyumi Arshed,
Levey Allan I.,
Goldstein Felicia C.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.043313
Subject(s) - candesartan , neurocognitive , lisinopril , medicine , randomized controlled trial , trail making test , neuropsychology , blood pressure , cognitive decline , psychology , cognition , dementia , angiotensin ii , psychiatry , angiotensin converting enzyme , disease
Background Observational studies suggest that angiotensin receptor blockers are associated with lower cognitive impairment. The CALIBREX (CAndesartan vs. LIsinopril effects on the BRain and Endothelial function in eXecutive MCI) trial aims to determine if this neurocognitive outcome in older adults with executive mild cognitive impairment (MCI) is due to blood pressure lowering effects or angiotensin receptors type 1 blockade. Method A randomized, double‐blind, clinical trial on a sample of 176 participants 55 years or older with mild cognitive impairment (MCI) and hypertension. Individuals were withdrawn from prior antihypertensive therapy and randomized to escalating doses of oral candesartan (up to 32 mg once daily) or lisinopril (up to 40 mg once daily). Open‐label antihypertensive drug treatments were added as needed to achieve blood pressure <140/90 mmHg. Participants underwent neuropsychological assessments at baseline, 6 and 12 months. The primary outcome was executive function (Trail Making Test Parts A and B, TMT) and secondary outcomes were episodic memory (Hopkins Verbal Learning Test‐Revised, HVLT‐R) and neuroimaging evidence of microvascular brain injury reflected by white matter lesions (WML). Outcome analyses followed an intention‐to‐treat approach with linear mixed models adjusted for trial group assignment and the interaction between time (visits) and trial group assignment. Result Of 176 randomized participants, 141 completed the trial (mean age=65 years; 55% women, 62% African Americans). Blood pressure control was equivalent for both groups but more participants withdrew from the lisinopril arm. At 12 months, the candesartan group had improved cognitive performance on TMT, B‐A (‐16.8 sec, 95% CI [‐30.3, ‐3.3]) while the lisinopril group had worse performance (11.5 sec [‐3.0, 26.0]; P‐value group*time=0.008). HVLT‐R delayed recall improved with candesartan by 1.0 (95% CI [0.3, 1.5]) whereas lisinopril improved by 0.3 (95% CI [‐0.3, 1.0]); P‐value group*time =0.026. There was no significant change in WML volume with candesartan (0.2 mm 3 , 95% CI [‐0.2, 0.7]) while the lisinopril group had a significant increase (0.9 mm 3 , 95% CI [0.4, 1.4]; P‐value group*time=0.06. Conclusion Candesartan demonstrates superior cognitive outcomes compared to lisinopril and may offer unique neurocognitive protection in older adults with executive MCI and hypertension.