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
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.
Available from: Mária A Deli
- "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
Available from: PubMed Central
- "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 . "
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ABSTRACT: Midlife cardiovascular risk factors, including diabetes, hypertension, dyslipemia, and an unhealthy lifestyle, have been linked to subsequent incidence, delay of onset, and progression rate of Alzheimer disease and vascular dementia. Conversely, optimal treatment of cardiovascular risk factors prevents and slows down age-related cognitive disorders. The impact of antihypertensive therapy on cognitive outcome in patients with hypertension was assessed in large trials which demonstrated a reduction in progression of MRI white matter hyperintensities, in cognitive decline and in incidence of dementia. Large-scale database correlated statin use and reduction in the incidence of dementia, mainly in patients with documented atherosclerosis, but clinical trials failed to reach similar conclusions.
Whether a multitargeted intervention would substantially improve protection, quality of life, and reduce medical cost expenditures in patients with lower risk profile has not been ascertained. This would require appropriately designed trials targeting large populations and focusing on cognitive decline as a primary outcome endpoint.
Cardiology Research and Practice 01/2011; 2011(3):250970. DOI:10.4061/2011/250970
Available from: Laura E Middleton
- "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   . However, the results from controlled trials (discussed below) are less consistent. "
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ABSTRACT: The prevalence of dementia is expected to increase dramatically over the upcoming decades due to the aging population. Since treatment is still short of a cure, preventative strategies are of the utmost importance. Stimulating activity (cognitive, physical, and social), vascular risk factors, and diet may be important in preventative strategies. Dementia risk may be modified by participation in stimulating activities. One study suggested that the cognitive, physical, and social components of activity were of equal importance to cognitive outcomes. However, while exercise interventions appear to benefit global cognition, the benefits from cognitive training appear to be domain specific. People with vascular risk factors (hypertension, diabetes, dyslipidemia, and obesity) appear to be at higher risk for dementia than those without in observational and clinical trials. Controlled trials suggest that vascular risk management via some pharmaceutical interventions may benefit cognition, though results are inconsistent. Finally, people who adhere to a Mediterranean diet or who have high intake of antioxidants and omega-3 fatty acids have reduced likelihood of dementia in observational studies. However, supplementation in controlled trials has not generally proved successful at improving cognitive outcomes. A single supplement may be insufficient to prevent dementia; it may be that the overall diet is more important. Future large randomized controlled studies should examine whether interventions can reduce the risk of dementia and whether combining cognitive, physical, and social activity, vascular risk reduction, and dietary interventions might have additive or multiplicative effects.
Journal of Alzheimer's disease: JAD 04/2010; 20(3):915-24. DOI:10.3233/JAD-2010-091657 · 4.15 Impact Factor
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