Jonathan Birns

Cognitive function and hypertension

The importance of lowering blood pressure (BP) in hypertensive subjects is well known but the relationship between hypertension and cognitive function is controversial. This article reviews the role of hypertension in the aetiology of cognitive impairment and the relationships between BP, cerebral perfusion and cognition. It also summarizes findings of studies addressing the effect of antihypertensive therapy and cognition. An electronic database search of MEDLINE, EMBASE and the Cochrane Library and extensive manual searching of articles were conducted to identify studies that have used objective measurements of BP and neuropsychological tests to investigate the relationship among hypertension, cognitive function and/or antihypertensive treatment. In total, 28 cross-sectional studies, 22 longitudinal studies and 8 randomized placebo-controlled trials met the inclusion criteria. Cross-sectional studies showed mixed relationships between higher BP and cognition, with many studies showing no correlation or even J- or U-shaped associations. The majority of longitudinal studies demonstrated elevated BP to be associated with cognitive decline. Randomized studies demonstrated heterogeneous and, sometimes conflicting, effects of BP lowering on cognitive function. Suggested reasons for this heterogeneity include multiple mechanisms by which hypertension affects the brain, the variety of cognitive instruments used for assessment and differences in antihypertensive treatments. Although lowering the BP is beneficial in most patients with vascular risk factors, the effects of BP reduction on cognition remain unclear. Given the predicted upswing in people with cognitive impairments, the time is right for randomized clinical trials with specific cognitive end points to examine the relationship between cognitive function and hypertension and guide practice.

The effects of blood pressure reduction on cognitive function : a review of effects based on pooled data from clinical trials

Objective To review systematically and synthesize quantitatively the evidence from completed randomized, controlled trials of blood pressure reduction on cognitive performance. Methods MEDLINE, EMBASE and Cochrane databases were searched to identify randomized, controlled trials that measured the effect of blood pressure reduction on cognitive performance. Additional studies were identified by searching bibliographies of retrieved articles and contacting experts in the field. Data were extracted on study quality, blood pressure, performance on cognitive function tests, antihypertensive treatment regimens and the duration of treatment. Studies were reviewed and abstracted independently by two trained researchers. Results Sixteen studies with 19 501 subjects were identified. Modest reductions in blood pressure (< 5/3 mmHg) in 13 860 subjects were associated with improvements in Mini Mental State Examination score [weighted mean difference (WMD) = 0.19; 95% confidence interval (CI) = 0.19–0.19] and performance on immediate (WMD = 0.62; 95% CI = 0.21–1.02) and delayed (WMD = 0.67; 95% CI = 0.23–1.11) logical memory tasks. However, studies in 2380 subjects that included tests of perceptual processing and learning capacity (trail making test-A, paired associated learning test) showed impaired performance (WMD = −1.12 s; 95% CI = −1.22 to −1.02 and WMD = −0.04; 95% CI = −0.04 to −0.04) on these tests. Conclusion Blood pressure lowering may have a heterogeneous effect on different aspects of cognitive function. Future studies with specific cognitive end-points are needed for greater clarity to guide practice.

Blood Pressure Reduction for Vascular Risk Is There a Price To Be Paid

The importance of lowering blood pressure (BP) in hypertensive subjects is well-known and recent studies suggest that lowering of BP in patients who may already be in the normotensive range further reduces the risk of vascular events, particularly stroke. Epidemiological data have also shown that lower BP and antihypertensive treatment may be associated with cognitive impairment once cerebrovascular disease is established. However, the relationship between hypertension and cerebrovascular disease is more complex than suggested by epidemiological or intervention studies. Cerebral imaging studies have shown that cerebral blood flow (CBF) is reduced in areas of small-vessel disease (SVD) and the degree of hypoperfusion correlates with disease severity. Furthermore, impaired neuropsychological performance has been found to correlate with cerebral hypoperfusion in patients with established SVD. These findings raise questions surrounding the desirability of lowering of BP beyond a certain level in such patients. It is conceivable that indiscriminate BP reduction may compromise cerebral perfusion and function in these patients, increasing the risk of cognitive decline and cerebrovascular disease progression. Randomized clinical trials addressing the relationship between antihypertensive treatment and vascular cognitive impairment are lacking. Further studies are therefore needed to assess the cognitive consequences of BP reduction in people with established cerebrovascular disease. This will help to direct appropriate protective strategies and treatments in a vulnerable group of people, many of whom have hypertension and cerebrovascular disease at the same time.

Cerebrovascular reactivity and dynamic autoregulation in ischaemic subcortical white matter disease

Background: It has been suggested that impaired cerebral autoregulation and vasodilatory capacity may play in role in the pathogenesis of the leukoaraiosis seen in small vessel disease. Adequate perfusion of the deep white matter of the brain depends on the relationships between blood pressure (BP), cerebral vasoreactivity and autoregulation. Methods: 24 h ambulatory BP measurement, quantitative volumetric MRI analysis of white matter lesion (WML) volume and transcranial Doppler ultrasound assessments of CO2 reactivity in response to hypercapnia and dynamic cerebral autoregulatory index (ARI) were undertaken in 64 patients with cerebral small vessel disease. Results: Subjects had mean 24 h BP 133/76 mm Hg (SD 13/9), median WML volume 7169 (IQR 20497) mm3, mean CO2 reactivity 83.6 (SD 37.4)% and mean ARI 5.6 (SD 1.4) (range 0–9). In multivariate models, after adjusting for age, gender, vascular risk profile and WML volume, ARI correlated with 24 h mean BP levels (R2 = 0.127, t = 2.440, p = 0.019) and CO2 reactivity correlated with duration of hypertension (R2 = 0.085, t = −2.244, p = 0.029). In individuals with hypertension for more than 10 years, ARI also correlated with nocturnal BP dipping (r = 0.806, p = 0.002). ARI and CO2 reactivity were unaffected by WML volumes, and ARI and CO2 reactivity were unrelated. Conclusion: Cerebral autoregulation and CO2 reactivity are two distinct processes which are not related to WML volume but are related to BP levels and duration of hypertension, respectively. Greater nocturnal dipping was associated with higher ARI values, suggesting preservation of autoregulation in patients with increased vulnerability to reduced cerebral perfusion.

Post‐stroke urinary incontinence

To provide a comprehensive review of the current evidence on post‐stroke urinary incontinence.

Telemedicine versus face-to-face evaluation in the delivery of thrombolysis for acute ischaemic stroke: a single centre experience

Background Telemedicine is increasingly used in the UK to deliver thrombolysis. It is primarily used to enable assessment of people presenting with an acute stroke by a remote specialist in stroke care, and to determine eligibility for thrombolysis with alteplase (recombinant tissue plasminogen activator). This study aims to evaluate the process of acute stroke care, safety and outcome profiles when comparing face-to-face evaluation and telemedicine in the delivery of thrombolysis. Methods This was a retrospective single centre cohort study, evaluating patients thrombolysed from July 2007 to December 2009 inclusive. All patients were given treatment within a 3-hour window from onset of symptoms. Of the 97 patients thrombolysed, 45 (46%) were evaluated by telemedicine. Process times of the steps taken to deliver thrombolysis for the two groups were compared. The authors include the rates of symptomatic intracranial haemorrhage (SICH). Outcome data include 3-month mortality and functional status. Results Process times were significantly better in face-to-face: Admission to CT (p=0.001), CT to treatment (p≤0.001) and admission to treatment (p≤0.001). SICH occurred in four patients (7.7%) in the face-to-face group compared with the two patients (4.4%) in the telemedicine group (p=0.7). Favourable outcome: a modified Rankin score of 0–2 was observed in 19 patients (36.5%) in the face-to-face group compared with 19 patients (42%) in the telemedicine group (p=0.9). Conclusions This analysis shows that the use of telemedicine compared with face-to-face evaluation is feasible in the delivery of thrombolysis during out of hours. There are several areas of our emergency process of hyper-acute stroke care that need improving when using telemedicine.

Blood pressure and vascular cognitive impairment: the debate continues.

The role of hypertension in the aetiology of vascular disease and the beneficial effects of antihypertensive treatment in preventing vascular events are well established. There is even evidence to suggest that antihypertensives treatment may reduce vascular risk, even in normotensive individuals. In contrast, the cognitive effects of blood pressure (BP) lowering remain a subject of considerable controversy. Epidemiological studies show conflicting results; although elevated BP in midlife has been associated with higher prevalence of white matter injury in the brain and cognitive decline in later years, lower BP in old age has been associated with poorer intellectual function. In addition, intervention studies with antihypertensives have shown opposing effects of BP reduction on cognitive function, further adding to the debate. Much of the controversy regarding the relationship between BP and cognition results from differences in definitions, subjects, methodologies and assessment techniques both for cognitive function and white matter disease between studies, as well as the confounding effects of antihypertensives treatment and comorbidities. In addition, very few studies have investigated the relationship between dynamic changes in BP, progression of white matter disease and cognitive performance in the same group of patients. The paper by van Boxtel et al. in this issue is the first study in which the relationship between BP, white matter disease load and cognitive performance has been examined systematically in the same cohort of subjects. BP was assessed using ambulatory 24-h BP measurement, which not only is superior to casual BP measurements in predicting hypertension-induced cerebrovascular disease but also allows the effects of physiological variations in BP to be assessed. The difficulties in assessing white matter disease progression are well known, and the use of previously validated MR techniques further strengthens the study. Estimation of structural damage has been complemented by assessment of cerebral function using quantifiable, reproducible and sensitive neuropsychological indices of executive dysfunction, the hallmark of hypertensive subcortical cerebral disease. Consistent with previous studies, van Boxtel et al. demonstrated higher systolic BP and pulse pressures to be related to the presence and severity of white matter lesion load. However, no clear relationship was demonstrated between white matter lesion load and cognitive performance parameters or between diurnal BP rhythm and structural or functional cerebral damage. Furthermore, small vessel disease load and cognitive performance was not affected by nocturnal dip in BP. It is generally accepted that hypertension accelerates arteriosclerotic changes in the brain predisposing to atheroma formation in large diameter blood vessels and arteriosclerosis and arteriolar tortuosity of small vessels (o400 mm) of the cerebral vasculature. These small arteries and arterioles undergo medial thickening with hyaline deposition and intimal proliferation, which results in a reduction of luminal diameter and increased resistance to flow. As arterial narrowing increases, it leads to a decline in the perfusion of the capillary bed, which can result in discrete regions of lacunar infarction and/or more diffuse ischaemic changes in the periventricular and deep white matter called leukoaraiosis. Chronic hypertension also predisposes to impaired blood brain barrier function, with endothelial cell retraction, increased vascular permeability and greater susceptibility to white matter injury for relatively small insults. The potential for white matter injury is further increased by the blood supply to the periventricular and deep white matter being dependent on end-arteries lacking appropriate anastamoses, thus creating an arterial watershed zone. Cerebral imaging studies have shown that cerebral blood flow is reduced in areas of small vessel disease and the degree of hypoperfusion correlates with disease severity. Furthermore, Correspondence: Professor L Kalra, Department of Stroke Medicine, Guy’s, King’s and St Thomas’s School of Medicine, Denmark Hill Campus, Bessemer Road, London SE5 9PJ, UK. E-mail: lalit.kalra@kcl.ac.uk Published online 29 September 2005 Journal of Human Hypertension (2006) 20, 1–3 & 2006 Nature Publishing Group All rights reserved 0950-9240/06

Ethnic differences in the cerebrovascular impact of hypertension.

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Recreational Drug Misuse and Stroke

Background: Small-vessel cerebrovascular disease and vascular cognitive impairment are more prevalent in hypertensive subjects of black African origin compared with Caucasians, but the relationships between blood pressure (BP), regional white matter damage and neuropsychological function have not been studied in well-characterised samples of subjects belonging to different ethnicities. Methods: Twenty-four-hour ambulatory BP, brain white matter lesion volumes on magnetic resonance imaging and executive cognitive function were compared in 41 Caucasian and 47 African-Caribbean subjects on optimal treatment attending a hypertension clinic. Results: African-Caribbean subjects were 4 years younger but had been hypertensive for 3 years longer than Caucasians. Their mean 24-hour systolic (136.6 vs. 129.4 mm Hg, p = 0.011) and diastolic (77.8 vs. 72.6 mm Hg, p = 0.006) BP were also higher despite being well-controlled. In multivariate models, African-Caribbean subjects had a greater parieto-occipital white matter lesion volume [adjusted difference: 319 mm3 (95% CI: 62–575), p = 0.016] and poorer performance on executive function [time difference: 0.375 s (95% CI: 0.191–0.558), p = 0.0001] and verbal fluency [score difference: –6.863 (95% CI: –12.531 to –1.195), p = 0.018] tests after adjusting for covariance in age, gender, vascular risk profile, duration of hypertension and education, and premorbid intelligence. Conclusions: African-Caribbean ethnicity was independently related to increased hypertensive white matter damage and executive cognitive dysfunction, the reasons for which merit further investigation.

The structural and functional consequences of diurnal variations in blood pressure in treated patients with hypertensive cerebrovascular disease

Stroke is the third commonest cause of death and single largest cause of adult disability worldwide. Whilst the majority of strokes in older individuals are due to large or small vessel arterial disease or cardiac disease in association with classical vascular risk factors, strokes occurring in younger individuals may have atypical etiologies. Recreational substance misuse is on the increase worldwide, particularly in young adults in developed countries with commonly used substances including cocaine, amphetamines, heroin and other opiates, marijuana and gammahydroxybutyrate (GHB). Adverse vascular sequelae of inappropriate use of these substances is well recognized but the link between acute stroke and substance misuse is often underestimated. Both ischemic and hemorrhagic strokes may be caused by recreational substance misuse and this paper reviews the available evidence and discusses the potential pathophysiological links.