Effect of baseline cognitive function and antihypertensive treatment on cognitive and cardiovascular outcomes: Study on COgnition and Prognosis in the Elderly (SCOPE).
ABSTRACT 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.
[Show abstract] [Hide abstract]
ABSTRACT: Secondary data analyses examined the differences in cognitive and instrumental activities of daily living (IADL) performance among hypertensive individuals taking one of four classes of antihypertensive medications, hypertensive individuals not taking any antihypertensive medications, and normotensive individuals (N=770). After adjusting for covariates, significant group differences were evident on all measures (speed of processing, motor speed, reaction time, ps < .05) except memory and Timed IADL (ps > .05). Follow-up a priori planned comparisons compared hypertensive individuals not on medications to each of the four antihypertensive medication groups. Results indicated that only those on beta blockers (BB) were significantly slower in speed of processing (ps < .05). A priori planned comparisons also revealed that normotensive individuals had better cognitive performance on measures of processing speed, motor speed, and reaction time than hypertensive individuals regardless of antihypertensive medication use. Additionally, normotensive individuals performed significantly better on memory (Digit and Spatial Span) than individuals with hypertension on medications. No differences were found between groups on memory (Hopkins Verbal Learning Test) or Timed IADL performance. With regard to antihypertensive medications, the use of BBs was associated with slowed processing speed. These analyses provide empirical evidence that hypertension primarily impacts speed of processing, but not severe enough to affect IADL performance. Given the contribution of processing speed to memory and executive function performance, this is an important finding. Clinicians need to take into consideration the potential negative impact that BBs may have on cognition when determining the best treatment of hypertension among older adult patients.Clinical Gerontologist 03/2013; 36(2):113-131. DOI:10.1080/07317115.2012.749322 · 0.66 Impact Factor
[Show abstract] [Hide abstract]
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; DOI:10.1007/s10571-014-0152-8 · 2.20 Impact Factor