Effect of Baseline Cognitive Function and Antihypertensive Treatment on Cognitive and Cardiovascular Outcomes: Study on COgnition and Prognosis in the Elderly (SCOPE)

Institute of Clinical Neurosciences, Neuropsychiatric Epidemiology Unit, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
American Journal of Hypertension (Impact Factor: 2.85). 08/2005; 18(8):1052-9. DOI: 10.1016/j.amjhyper.2005.02.013
Source: PubMed


We examined whether cognitive function at baseline affected cognitive and cardiovascular outcomes in the Study on COgnition and Prognosis in the Elderly (SCOPE), a blood pressure (BP)-lowering intervention trial.
SCOPE included 4937 patients, aged 70 to 89 years, with mild-to-moderate hypertension and Mini Mental State Examination (MMSE) score > or =24. Double-blind treatment was initiated with candesartan or placebo. Open-label therapy was added as needed to control BP, both in the candesartan (49%) and control (66%) groups. Mean follow-up was 3.7 years. Low cognitive function (LCF) at baseline was defined as MMSE score 24 to 28 (N = 2070), and high cognitive function (HCF) as MMSE score 29 to 30 (N = 2867).
Mean BP reductions were approximately 20/10 mm Hg both in LCF and HCF patients, with greater reductions in the candesartan group than in the control group. The incidence of dementia was higher in LCF than in HCF patients. A higher cardiovascular event rate observed in LCF patients was explained by older age and other cardiovascular risk factors at baseline. In LCF patients, the MMSE score declined less in the candesartan than in the control group (mean difference 0.49, 95% confidence interval 0.02 to 0.97, P = .04). Nonfatal stroke was reduced in the candesartan group in the total sample (28%, P = .04), with no difference between LCF (27%) and HCF (29%) patients.
Elderly patients with mild-to-moderate hypertension and slightly impaired cognitive function (MMSE 24 to 28) are at increased risk of dementia and cardiovascular events. This analysis indicates that effective antihypertensive therapy may reduce cognitive decline and stroke incidence in these patients.

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    • "As the RAS components exist in vascular systems as well as in the central nervous system, candesartan appears to affect both vascular and neural systems. Indeed, several reports have indicated that candesartan improves neuronal damage and cognitive impairment caused by cerebral ischemia (Lu et al. 2005; Skoog et al. 2005). In contrast, the consequences of AT 1 receptor blockade on the cerebral vascular system are controversial. "
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    ABSTRACT: Candesartan has been reported to have a protective effect on cerebral ischemia in vivo and in human ischemic stroke. We studied the direct effects of candesartan on blood-brain barrier (BBB) function with our in vitro monolayer model generated using rat brain capillary endothelial cells (RBECs). The in vitro BBB model was subjected to normoxia or 6-h oxygen glucose deprivation (OGD)/24-h reoxygenation, with or without candesartan. 6-h OGD/24-h reoxygenation decreased transendothelial electrical resistance and increased the endothelial permeability for sodium fluorescein in RBEC monolayers. Candesartan (10 nM) improved RBEC barrier dysfunction induced by 6-h OGD/24-h reoxygenation. Immunostaining and immunoblotting analysis indicated that the effect of candesartan on barrier function under 6-h OGD/24-h reoxygenation was not related to the expression levels of tight junction proteins. However, candesartan affected RBEC morphological changes induced by 6-h OGD/24-h reoxygenation. We analyzed oxidative stress and cell viability using chemical reagents. Candesartan improved cell viability following 6-h OGD/24-h reoxygenation, whereas candesartan had no effect on oxidative stress. These results show that candesartan directly improves cell function and viability of brain capillary endothelial cells under OGD/reoxygenation, suggesting that the protective effects of candesartan on ischemic stroke are related to protection of the BBB.
    Cellular and Molecular Neurobiology 12/2014; 35(4). DOI:10.1007/s10571-014-0152-8 · 2.51 Impact Factor
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    • "Among patients with a low baseline cognitive function, the MMSE score declined less in the candesartan group (mean difference 0.49, P = .04). Of note, patients with a low baseline cognitive function were older and had more cardiovascular risk factors [45]. "
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    Cardiology Research and Practice 01/2011; 2011(3):250970. DOI:10.4061/2011/250970
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    • "In observational studies, this appears to be the case. People with hypertension who took antihypertensives had lower risk of dementia than those who do not [64] [65] [66]. However, the results from controlled trials (discussed below) are less consistent. "
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