Dataset Information

Antihypertensive therapy and cerebral hemodynamics in executive mild cognitive impairment: results of a pilot randomized clinical trial.

ABSTRACT:

Objectives

To compare the effects of three antihypertensive medications on cerebral hemodynamic and cognitive function in hypertensive individuals with executive dysfunction.

Design

Double-blind randomized clinical trial.

Setting

Community.

Participants

Fifty-three individuals aged 60 and older with hypertension and executive dysfunction.

Intervention

Lisinopril, candesartan, or hydrochlorothiazide for 1 year.

Measurements

Cerebral blood flow velocity (BFV; transcranial Doppler ultrasonography during rest, sitting, standing, hypercapnia, and hypocapnia), cognition, and blood pressure were measured at baseline and after 6 and 12 months. Linear mixed models were used to compare the three groups.

Results

Of the 53 participants, 47 had successful insonation (mean age 72; 70% white; 57% women). There was a tendency toward an increase in BFV in the candesartan group and a decrease in the lisinopril and hydrochlorothiazide groups (between-group P = .57) that was significant in those with low BFV at baseline (ConclusionAngiotensin receptor blockers may preferentially preserve cerebral hemodynamics and executive function in individuals with executive dysfunction. These findings warrant further investigation in a larger trial.

SUBMITTER: Hajjar I

PROVIDER: S-EPMC3608194 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Publications

Antihypertensive therapy and cerebral hemodynamics in executive mild cognitive impairment: results of a pilot randomized clinical trial.

Hajjar Ihab I Hart Meaghan M Chen Yu-Ling YL Mack Wendy W Novak Vera V C Chui Helena H Lipsitz Lewis L

Journal of the American Geriatrics Society 20130125 2

<h4>Objectives</h4>To compare the effects of three antihypertensive medications on cerebral hemodynamic and cognitive function in hypertensive individuals with executive dysfunction.<h4>Design</h4>Double-blind randomized clinical trial.<h4>Setting</h4>Community.<h4>Participants</h4>Fifty-three individuals aged 60 and older with hypertension and executive dysfunction.<h4>Intervention</h4>Lisinopril, candesartan, or hydrochlorothiazide for 1 year.<h4>Measurements</h4>Cerebral blood flow velocity ( ...[more]

PMID: 23350899

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Project description:BackgroundTranscranial direct current stimulation (tDCS), a non-invasive stimulation, represents a potential intervention to enhance cognition across clinical populations including Alzheimer's disease and mild cognitive impairment (MCI). This randomized clinical trial in MCI investigated the effects of anodal tDCS (a-tDCS) delivered to left inferior frontal gyrus (IFG) combined with gist-reasoning training (SMART) versus sham tDCS (s-tDCS) plus SMART on measures of cognitive and neural changes in resting cerebral blood flow (rCBF). We were also interested in SMART effects on cognitive performance regardless of the tDCS group.MethodsTwenty-two MCI participants, who completed the baseline cognitive assessment (T1), were randomized into one of two groups: a-tDCS + SMART and s-tDCS + SMART. Of which, 20 participants completed resting pCASL MRI scan to measure rCBF. Eight SMART sessions were administered over 4 weeks with a-tDCS or s-tDCS stimulation for 20 min before each session. Participants were assessed immediately (T2) and 3-months after training (T3).ResultsSignificant group × time interactions showed cognitive gains at T2 in executive function (EF) measure of inhibition [DKEFS- Color word (p = 0.047)], innovation [TOSL (p = 0.01)] and on episodic memory [TOSL (p = 0.048)] in s-tDCS + SMART but not in a-tDCS + SMART group. Nonetheless, the gains did not persist for 3 months (T3) after the training. A voxel-based analysis showed significant increase in regional rCBF in the right middle frontal cortex (MFC) (cluster-wise p = 0.05, k = 1,168 mm3) in a-tDCS + SMART compared to s-tDCS + SMART. No significant relationship was observed between the increased CBF with cognition. Irrespective of group, the combined MCI showed gains at T2 in EF of conceptual reasoning [DKEFS card sort (p = 0.033)] and category fluency [COWAT (p = 0.055)], along with gains at T3 in EF of verbal fluency [COWAT (p = 0.009)].ConclusionOne intriguing finding is a-tDCS to left IFG plus SMART increased blood flow to right MFC, however, the stimulation seemingly blocked cognitive benefits of SMART on EF (inhibition and innovation) and episodic memory compared to s-tDCS + SMART group. Although the sample size is small, this paper contributes to growing evidence that cognitive training provides a way to significantly enhance cognitive performance in adults showing memory loss, where the role of a-tDCS in augmenting these effects need further study.

Project description:Background: Mild cognitive impairment (MCI) is considered to be a transitional state between normal aging and Alzheimer's dementia (AD). Recent studies have indicated that executive function (EF) declines during MCI. However, only a limited number of studies have investigated the neural basis of EF deficits in MCI. Herein, we investigate the changes of regional brain spontaneous activity and functional connectivity (FC) of the executive control network (ECN) between high EF and low EF groups. Methods: According to EF composite score (ADNI-EF) from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we divided MCI into two groups, including the MCI-highEF group and MCI-lowEF group. Resting-state functional MRI was utilized to investigate the fractional amplitude of low-frequency fluctuation (fALFF) and ECN functional connectivity across 23 healthy controls (HC), 11 MCI-highEF, and 14 MCI-lowEF participants. Moreover, a partial correlation analysis was carried out to examine the relationship between altered fALFF or connectivity of the ECN and the ADNI-EF. Results: Compared to HC, the MCI-highEF participants demonstrated increased fALFF in the left superior temporal gyrus (STG), as well as decreased fALFF in the right precentral gyrus, right postcentral gyrus, and left middle frontal gyrus (MFG). The MCI-lowEF participants demonstrated increased fALFF in the cerebellar vermis and decreased fALFF in the left MFG. Additionally, compared to HC, the MCI-highEF participants indicated no significant difference in connectivity of the ECN. Furthermore, the MCI-lowEF participants showed increased ECN FC in the left cuneus and left MFG, as well as decreased ECN functional connectivity in the right parahippocampal gyrus (PHG). Notably, the altered fALFF in the left MFG was positively correlated to ADNI-EF, while the altered fALFF in cerebellar vermis is negatively correlated with ADNI-EF across the two MCI groups and the HC group. Altered ECN functional connectivity in the right PHG is negatively correlated to ADNI-EF, while altered ECN functional connectivity in the left cuneus is negatively correlated to ADNI-EF across the three groups. Conclusions: Our current study demonstrates the presence of different patterns of regional brain spontaneous activity and ECN FC in the MCI-highEF group and MCI-lowEF group. Furthermore, the ECN FC of the MCI-highEF group was not disrupted, which may contribute to retained EF in MCI.

Project description:BackgroundCerebral microvascular dysfunction is commonly seen in Alzheimer's disease (AD) and vascular cognitive impairment (VCI). Cerebrovascular reactivity (CVR) to CO2 reflects cerebral microvascular health and may be modulated by the renin-angiotensin system (RAS). This study aimed to investigate the effects of RAS modulation on CVR in individuals with mild cognitive impairment (MCI) due to underlying vascular or AD etiologies.MethodsThis 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 CO2 challenge at baseline and 12 months. Regions of interest and voxel-wise CVR maps were derived from BOLD signal changes during CO2 challenge. CVR effects were compared between candesartan and lisinopril (CALIBREX) and candesartan and placebo (CEDAR) using mixed-model repeated measures.ResultsData 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.ConclusionThis 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.

Dataset Information

Antihypertensive therapy and cerebral hemodynamics in executive mild cognitive impairment: results of a pilot randomized clinical trial.

Objectives

Design

Setting

Participants

Intervention

Measurements

Results

Publications

Antihypertensive therapy and cerebral hemodynamics in executive mild cognitive impairment: results of a pilot randomized clinical trial.

Similar Datasets

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