lisinopril and Cognitive-Dysfunction

Cerebral microvascular dysfunction is commonly seen in Alzheimer's disease (AD) and vascular cognitive impairment (VCI). Cerebrovascular reactivity (CVR) to CO. This study presents findings of candesartan's effects on the secondary outcomes of two double-blind randomized clinical trials of 12-month therapy of candesartan versus lisinopril in VCI (CALIBREX (Candesartan vs Lisinopril Effects on the Brain and Endothelial Function in Executive MCI)) and candesartan versus placebo in prodromal AD (Candesartan's Effects on Alzheimer's Disease and Related Biomarkers (CEDAR)). Primary outcome results of these trials have been reported in previous publications. Participants underwent identical brain blood oxygenation level dependent (BOLD)-CVR in response to a 2-min CO. Data from 102 participants in the CALIBREX study (mean age = 65 years, 45% female, 63% African American) and 59 in the CEDAR study (mean age = 67 years, 32% female, 20% African American) were analyzed. Candesartan was associated with improved whole brain CVR compared to placebo in the CEDAR study (adjusted within-group mean difference for candesartan = 0.27 (95% confidence interval (CI) = 0.006, 0.53) vs placebo = -0.17 (95% CI = 0.42, 0.08), p-value = 0.018), and compared to lisinopril in the CALIBREX study (adjusted within-group mean difference for candesartan = 0.28 (95% CI = 0.10, 0.46) vs lisinopril = -0.08 (95% CI = -0.31, 0.14), p-value = 0.012), independent of blood pressure. In an exploratory meta-analysis of the two trials, improved CVR in the hippocampus was linked to improved attention and working memory (p = 0.044) and a trend for improved executive function (p = 0.087) with candesartan therapy.. This study suggests that candesartan is associated with improved microvascular function in MCI, and these findings are independent of its blood pressure effect in these VCI and prodromal AD populations.

Topics: Aged; Alzheimer Disease; Carbon Dioxide; Cognitive Dysfunction; Female; Humans; Lisinopril; Male; Randomized Controlled Trials as Topic; Stroke

Four patients experienced visual hallucinations that appear to have been precipitated by lisinopril. Other cases of visual hallucinations have been reported with other angiotensin-converting enzyme (ACE) inhibitors. Older patients, particularly those with a history of either dementia or mild cognitive impairment, may be at higher risk. Hallucinations resolved within 1 to 30 days after cessation of ACE inhibitors. Development of visual hallucinations after initiation of ACE inhibitors should prompt discontinuation of therapy. Visual hallucinations have been reported in one case involving an ARB. Visual hallucinations have not been associated with direct renin inhibitors. Consideration should be given to use of alternative, unrelated antihypertensive drug classes.

Topics: Age Factors; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Cognitive Dysfunction; Comorbidity; Dementia; Female; Hallucinations; Humans; Hypertension; Lisinopril; Male; Risk Factors; Withholding Treatment

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.. To determine neurocognitive effects of candesartan vs lisinopril in older adults with mild cognitive impairment (MCI).. 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.. 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.. 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.. 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]).. 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.. ClinicalTrials.gov Identifier: NCT01984164.

Topics: Administration, Oral; Aged; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Brain; Cognitive Dysfunction; Female; Humans; Hypertension; Lisinopril; Magnetic Resonance Imaging; Male; Middle Aged; Tetrazoles