Concomitant Cerebrovascular Disease Research Articles

Applied Neuromonitoring and Improving Central Nervous System Outcomes

This article will review the pathogenesis of perioperative neurological injury in patients undergoing coronary revascularization. The high percentage of such patients with diabetes or concomitant cerebrovascular disease renders this population particularly susceptible to injury as a consequence of both hypoperfusion and atheroemboli. The role of transesophageal echocardiography for assessment of ascending aortic atherosclerosis and the use of noninvasive cerebral oximetry to detect cerebral hypoperfusion are discussed with respect to their impact on patient outcomes.

Number of children is associated with neuropathology of Alzheimer's disease in women

Objective To examine the association between number of born children and neuropathology of Alzheimer's disease (AD). Methods The brains of 86 subjects with data on the number of biological children born, were studied postmortem. Primary analyses included 73 subjects (average age at death = 80; 42 women) devoid of cerebrovascular disease associated lesions (i.e., infarcts) or of non-AD related neuropathology. Women were significantly older at death than men (85.6 vs. 73.4; p < .0005) but did not differ significantly from men in number of children or dementia severity. Secondary analyses included 13 additional subjects who had concomitant cerebrovascular disease. Density of neuritic plaques (NPs) and neurofibrillary tangles (NFTs) in the hippocampus, entorhinal cortex, amygdala and multiple regions of the cerebral cortex, as well as composites of these indices reflecting overall neuropathology, were analyzed. For men and women separately, partial correlations, controlling for age at death and dementia severity, were used to assess the associations of number of children with these neuropathological variables. Results Among women, all the partial correlations were positive, with statistical significance for overall neuropathology ( r = .37; p = .02), overall NPs ( r = .36; p = .02), and for NPs in the amygdala ( r = .47; p = .002). Among men, none of the partial correlations were statistically significant. Results of the secondary analyses were similar. Conclusions Since the associations between number of children and neuropathology of AD were found for women only, they might reflect sex-specific mechanisms (such as variations in estrogen or luteinizing hormone levels) rather than social, economic, biological or other mechanisms common to both men and women.

Abstract 3430: Ethnic Differences in the Prevalence and Treatment of Cardiovascular Risk Factors in Outpatients with Peripheral Arterial Disease: Insights from the REACH Registry

Background : In the United States, African Americans have been reported to have an increased prevalence of peripheral arterial disease (PAD) with poorer outcomes as compared to whites. Whether this can be attributed to differences in the presence and treatment of traditional coronary artery disease (CAD) risk factors versus other factors specifically related to ethnicity is unknown. Methods : We identified 2,235 patients from the United States with documented PAD with and without concomitant CAD and cerebrovascular disease (CVD) at one year enrolled in the REduction of Atherothrombosis for Continued Health (REACH) Registry. We compared the baseline demographics, risk factor profiles, medication use, and one-year outcomes between the 236 African Americans and 1,810 non-Hispanic whites. Results : Among the traditional atherosclerotic risk factors, African Americans were more likely than whites to have diabetes (64.0% vs. 48.6%, p&lt;0.0001), hypertension (95.3% vs. 86.5%, p=0.0001), obesity (45.9% vs. 34.3%, p=0.0002), and isolated PAD (44.9% vs. 28.7%, p&lt;0.0001). In comparison to whites, African Americans were less likely to be on aspirin (62.0% vs. 72.4%, p=0.0009) and lipid-lowering therapy (76.1% vs. 83.2%, p=0.0071), and more likely to have an elevated blood pressure (BP ≥140/90 mmHg: 54.9% vs. 38.1%, p&lt;0.0001) and fasting cholesterol (&gt;200 mg/dL: 41.7% vs. 24.9%, p&lt;0.0001) at baseline. Overall, there were no significant difference in all-cause mortality (4.70% vs. 5.32%, p=0.97) or CV death, MI, or stroke (4.92% vs. 6.20%, p=0.79) between African Americans and whites in this cohort (data adjusted for age and sex). Conclusion : Among U.S. outpatients with PAD, African Americans are more likely than whites to have risk factors for cardiovascular disease, but less likely to receive aspirin or lipid-lowering therapy. In this registry, one-year event rates are relatively high, but similar in both groups.

Donepezil in Alzheimer's disease: a clinical observational study evaluating individual treatment response

ABSTRACTObjective: A post-marketing surveillance study evaluating the sensitivity of the Individual Symptom Score (IndiSS) in assessing the treatment benefits of donepezil in patients with Alzheimer's disease (AD) under everyday conditions.Research design and methods: For each patient, up to three ‘especially relevant’ individual symptoms were defined and evaluated during donepezil treatment. Changes were scored on a five-point Likert-type scale, ranging from ‘markedly improved’ (+2) to ‘markedly worsened’ (–2). The mean score for all IndiSS items was calculated after 3 and 6 months. Positive values represented treatment success. In addition, patients with concomitant parkinsonian symptoms (PS+) or cerebrovascular disease (CVD+) were compared with those with neither condition.Results: A total of 2046 patients with AD enrolled. The most frequent IndiSS items were (% patients): memory (24%), disorientation (14%) and loss of initiative/apathy (9%). The mean IndiSS for the overall patient population was +0.7 ± 0.7 points after 3 months and +0.9 ± 0.8 after 6 months. Patients with concomitant PS+ or CVD+ showed similar improvements in IndiSS.Conclusion: Identification and follow-up of individual symptoms is a useful tool for evaluating therapy response to donepezil in everyday practice. Patients with concomitant PS+ or CVD+ benefit from donepezil therapy and show a similar side-effect profile.

Cognitive function in patients with alzheimer's dementia and concomitant cerebrovascular disease treated with galantamine - a one year open-label phase-IIIb-study

Cognitive function in patients with alzheimer's dementia and concomitant cerebrovascular disease treated with galantamine - a one year open-label phase-IIIb-study

P2-399: Efficacy and tolerability of galantamine in patients with Alzheimer’s dementia and concomitant cerebrovascular disease

P2-399: Efficacy and tolerability of galantamine in patients with Alzheimer’s dementia and concomitant cerebrovascular disease

Medical management of intermittent claudication.

The symptoms of intermittent claudication (IC) lead sufferers to seek medical attention, potentially leading to substantial workup and invasive testing. However, only a minority of people with IC develop limb-threatening ischemia or symptoms of significant lifestyle-limiting claudication. Patients with IC have a substantial risk of concomitant cardiovascular and cerebrovascular disease. Assessment of co-morbidities and control of risk factors reduce the cardiovascular risk of these patients. A multitude of drugs have been developed and tested in numerous trials for the symptoms of IC. Although no drug alone offers a "cure" to IC, some are used as adjuvant therapy to reduce claudication symptoms.

Predictors of mortality in patients with peripheral vascular disease. A prospective follow-up study

Background Peripheral vascular disease is associated with increased cardiovascular mortality and reduced life expectancy. The main causes of death are due to concomitant coronary heart and cerebrovascular disease. Objective To assess the long-term survival of patients with PVD and to investigate the impact of the presence of risk factors on mortality. Design Cohort study of patients with intermittent claudication and angiographically established PVD. Baseline investigations were performed in 1990—2; follow-up continued until 1999. Setting St George's Hospital in South London. Patients One hundred and ten consecutive patients (66 men and 44 women) referred electively for PVD and who underwent lower limb digital subtraction angiography. Main outcome measures Survival rates, all-cause mortality. Results Sixty-one patients (55.4%) died during the follow-up period (26 from cardiovascular causes). The overall five-year survival rate was 52% (95% C.I. 42—62). The survival rate was significantly lower in patients older than 70 years (38% [26—51]) compared to those 70 years or younger (69% [54—80])(p&lt;0.05). The risk of all-cause mortality was almost two-fold in the older than younger age group (sex-adjusted hazards ratio 1.89 [1.08—3.10]). The presence of diabetes at the baseline was an important predictor of survival. After adjusting for age and sex diabetic patients had a hazards ratio of 1.79 (0.96—3.37) compared to non-diabetic patients for all-cause mortality. Further adjustment for hypertension, smoking and renal impairment did not attenuate the risk estimate. Hypertension, smoking and the presence of renal artery stenosis were associated with greater risk of all-cause mortality, although none of these estimates reached statistical significance. Conclusions Age and presence of diabetes are important independent prognostic factors for increased mortality in patients with peripheral vascular disease.

Bioequivalence Study of Nicardipine Solution Versus Nicardipine Tablets

The bioequivalence of a solution (investigational product) and a tablet (reference product) formulation of the dihydropyridine‐type derivative Ca2 + antagonist nicardipine were investigated by measuring plasma levels of the compound after single randomized administration of 20 mg of the two formulations. Drugs were given orally in a single dose to 24 healthy volunteers (12 males and 12 females) at the beginning of the experiment and after a two weeks wash‐out. Nicardipine is available in oral and intravenous formulations, the second being used for the short‐term treatment of hypertensive crises. Oral formulations of nicardipine most diffused include immediate release (20 or 30 mg, three times a day administration), sustained release (30 mg, 45 mg or 60 mg, twice a day administration) and modified release (80 mg, once a day administration) tablets. A nicardipine solution is available only in Spain, but no published studies on the kinetics of this formulation are available. In the last 15 years, the main efforts were aimed to develop sustained or controlled release formulations of nicardipine to improve patient compliance by reducing the number of doses required each day. However, the use of twice a day or once a day administration of Ca2 + antagonists should be not overemphasized in particular situations like those of possible risk of cerebrovascular and/or coronary steal effect primarily in the elderly. The oral formulation of nicardipine investigated with a bioequivalence range > 70% compared to nicardipine immediate release tablets may represent an additional resource for treating elderly patients with concomitant cerebrovascular or coronary heart disease.

Vascular dementia.

Vascular dementia has an unusual history. It ceased to be the most common type of dementia because of a change of opinion rather than a change in reality, and recent attempts to develop rigorous diagnostic criteria for vascular dementia could have made it even more rare. It is ironic that clinics and long-term care facilities are full of patients who have both dementia and cerebrovascular disease, but explicit management recommendations for vascular dementia are few, in part because it is difficult to recruit adequate numbers of “pure” vascular dementia for clinical trials. The following discussion of vascular dementia will examine the concept, review the variety of vascular dementias, enumerate diagnostic criteria, and consider the opinion that Alzheimer and vascular pathology can exist together more often than in isolation. A discussion of management will then appropriately consider the management of concomitant dementia and cerebrovascular disease, rather than be confined to the somewhat artificial construct of “pure” vascular dementia.

Epilepsy in the Elderly

Epilepsy in the Elderly

Treatment with donepezil in Alzheimer patients with and without cerebrovascular disease

Donepezil, a selective acetylcholinesterase inhibitor, is approved for the symptomatic treatment of mild to moderate Alzheimer's disease (AD). In a post-marketing surveillance (PMS) study in Germany, patients under routine treatment conditions were observed while treatment was switched from other antidementia drugs (i.e., nootropics) to donepezil. A total of 913 patients were enrolled (60.1% female, mean±S.D. age 73.4±8.6 years, mean Mini-Mental Status Examination [MMSE] 18.0±5.3), and were treated with donepezil (5 or 10 mg/day according to recommended dosing). 709/913 (77.1%) of patients had been pretreated with other antidementive drugs (piracetam, memantine, ginkgo, and others). In 29.6% of patients, investigators documented concomitant cerebrovascular disease (CVD+) according to their clinical judgment. Observation period was 3 months for the individual patient. Efficacy parameters were changes in MMSE, global clinical (investigators) judgment of efficacy, and a clinical judgment about the patients' quality of life (QoL). Adverse events were also analyzed. The objective of the present investigation was to compare—in a “real-life” setting—the differential efficacy and tolerability of donepezil in AD patients with and without concomitant cerebrovascular disease. After 3 months, patients had improved by a mean MMSE change from baseline of 2.2 points (CVD+: 2.4 pts, CVD−: 2.1 pts). QoL was judged “improved” in 70.0% of patients (CVD+: 72.5%, CVD−: 69.6%). Adverse events were reported in 85/913 (9.3%) of patients (CVD+: 11.2%, CVD−: 7.9%). Reported adverse events were substantially less than reported previously in controlled clinical trials. This suggests that donepezil therapy is effective and well tolerated in AD patients, both with and without concomitant cerebrovascular disease.

Treatment options: The latest evidence with galantamine (Reminyl®)

Vascular dementia (VaD) has a great deal of overlap (in terms of features and symptoms) with Alzheimer's disease (AD). Mixed dementia, or AD with concomitant cerebrovascular disease (AD with CVD), is increasingly being recognized as a distinct clinical condition that occurs with substantial frequency. The robust evidence for the effectiveness of cholinergic treatments such as galantamine (Reminyl®) in AD suggests its potential use in the treatment of dementias related to CVD, and preclinical evidence supports this rationale. Galantamine, which has a unique dual cholinergic mode of action, may be of particular benefit in VaD and AD with CVD. For example, behavioral symptoms, which can be more severe in VaD than in AD and are important determinants of the impact of dementia, may be especially benefited by galantamine. This results from its potential to modulate systems involving other neurotransmitters such as 5-HT (serotonin) and dopamine, which affect mood and emotional balance. The results of a recent landmark clinical trial with galantamine in patients with VaD, or AD with CVD, indicate that galantamine produces benefits across a broad range of symptoms of dementia in both patient populations. Significant cognitive improvements over 6 months, long-term maintenance of cognition for at least 12 months, and global benefits, as well as efficacy in both behavioral and functional symptoms, indicate efficacy with galantamine that is so far unsurpassed by any other drug treatment for dementia. Galantamine therefore has potential to benefit a wide range of patients with dementia in the clinic.

Diagnosis of peripheral arterial disease: Utility of the vascular laboratory

The risks of undiagnosed peripheral arterial disease (PAD) include progressive reduction in quality of life, potential limb loss, and unrecognized comorbid atherosclerotic (concomitant coronary and cerebrovascular) disease. Although a thorough historical review of symptoms and a comprehensive physical examination may lead the clinician to an appropriate index of suspicion, accurate diagnostic testing is crucial. Accredited vascular diagnostic laboratories provide a risk free description of the presence, severity, and location of PAD. This article describes the basic noninvasive diagnostic tests, criteria for diagnosis, advantages and disadvantages of each diagnostic modality, and a strategy for PAD therapy.

Predictors of overall and cardiovascular mortality in peripheral arterial disease

Survival rates in patients with intermittent claudication and in patients with critical leg ischemia (CLI) have never been compared directly in a western population, and no report has yet determined the prognostic significance of the 2 clinical presentations of peripheral arterial disease (PAD) in long-term follow-up. Most observational studies have examined patients with critical1,2 and noncritical3–7 leg ischemia separately, or have reported the prognostic value of the ankle-brachial blood pressure index.8–11 We conducted a study to determine whether CLI is an independent risk factor for all-cause and cardiovascular mortality, paying attention to the confounding effect of other prognostic factors, including traditional cardiovascular risk factors and concomitant cardiac and cerebrovascular disease.

Influence of treatment with Ca 2+ antagonists on cerebral vasculature of spontaneously hypertensive rats

Hypertension is the main cause of stroke that represents the second most common cause of death in the industrialized world and a leading cause of inability of the elderly. Lowering blood pressure reduces cerebrovascular morbidity and mortality, but it is still controversial if blood pressure should be lowered in elderly individuals with concomitant cerebrovascular disease. The present study has analyzed comparatively the effect of treatment with the dihydropyridine-type Ca 2+ channel blockers lercanidipine, manidipine and nimodipine and with the non dihydropyridine-type vasodilator hydralazine on hypertension-dependent cerebrovascular changes in spontaneously hypertensive rats (SHR). Analysis included medium and small sized pial arteries and intracerebral arteries of frontal cortex, hippocampus, striatum, and cerebellum. In control SHR, systolic pressure (SBP) values were significantly higher in comparison with WKY rats. Pharmacological treatment significantly decreased SBP values, with nimodipine reducing only moderately SBP. In control SHR, thickening of arterial wall accompanied by luminal narrowing with consequent increase of the wall-to-lumen ratio occurred both in pial and intracerebral arteries. Dihydropyridine-type Ca 2+ antagonists and to a lesser extent hydralazine countered these morphological alterations. Lercanidipine displayed a particular activity on small sized intraparenchymal brain arteries, where it was more effective than other compounds tested. This activity of lercanidipine on small-sized intracerebral arteries might represent an interesting property for the treatment of hypertensive brain damage with concomitant ischemia.

Epilepsy in elderly people.

The prevalence and incidence of epilepsy are highest in later life with around 25% of new cases occurring in elderly people, many of whom will have concomitant neurodegenerative, cerebrovascular, or neoplastic disease. Difficulties accepting the diagnosis are frequently compounded by its unpredictable nature. Those affected commonly lose confidence and independence. Seizures in older people can result in physical injury, adding to low morale. Complete control is achievable in around 70% of patients with antiepileptic drug treatment. Optimum management requires rapid investigation, accurate diagnosis, effective treatment, sympathetic education, and assured support. The emergence of seizure disorders in old age places an increasing burden on health-care facilities and costs. A coordinated programme among health-care workers is advised to maintain the independence and improve the quality of life of this vulnerable patient population.

Prothrombin fragments F1+2, thrombin–antithrombin III complexes, fibrin monomers and fibrinogen in patients with coronary atherosclerosis

We determined the plasma levels of prothrombin fragment F1+2, thrombin–antithrombin III complexes (TAT), fibrin monomers (FM), d-dimers (DD) and fibrinogen in 57 patients with angiographically verified graded coronary artery disease (CAD) free of concomitant peripheral atherosclerosis, cerebrovascular disease or diabetes mellitus and a group of 21 apparently healthy controls. Blood was collected from the antecubital vein through atraumatic venipuncture prior to the angiographic procedure. Plasma levels of hemostatic markers were related to the presence and graded severity of CAD. The levels of prothrombin fragment F1+2 (1.74±0.11 vs. 1.0±0.07 nmol/l, P<0.001), FM (41.6±5.5 vs. 7.42±3.05 nmol/l, P<0.001), TAT (15.6±2.7 vs. 2.96±0.32 μg/l, P<0.001) and fibrinogen (3.64±1.3 vs. 3.08±0.33 g/l, P<0.01) were significantly higher in patients with CAD compared to controls, while there was no difference regarding the fibrinolytic system represented by DD (441.6±58.9 vs. 337.4±42.05 μg/l, n.s.). Within the CAD group, patients with extensive coronary atherosclerosis (≥2 vessel disease) had significantly higher values for prothrombin fragment F1+2 (1.89 vs. 1.57 nmol/l, P=0.04), FM (50.7 vs. 29.8 nmol/l, P=0.03), and a trend to significance was noted for fibrinogen (3.9 vs. 3.3 g/l, P=0.07) suggesting that blood coagulability was related to the severity of the disease and that hemostatic markers of thrombin activity represent a useful tool to identify patients with a latent hypercoagulable state with a higher susceptibility to sustain coronary thrombosis.

Treatment of Carotid Artery Stenosis by Elective Stent Placement Instead of Carotid Endarterectomy in Patients with Severe Coronary Artery Disease

Patients with concomitant cardiac and cerebrovascular disease undergoing revascularization procedures are at high risk of both, cardiac and cerebrovascular complications. The purpose of our study was to evaluate the feasibility of prior elective carotid artery stenting as an alternative treatment procedure to carotid endarterectomy (CEA) in patients with concomitant coronary artery disease (CAD), who clearly needed coronary revascularization. We offered extracranial internal carotid stenting to 85 patients with 89 significant carotid stenoses. Out of these, 19 patients were symptomatic. The quantitative mean reduction in diameter was 77 +/- 11%. Stent implantation was successful in 88 lesions. Two disabling major and 3 reversible minor strokes occurred periprocedurally. Three patients showed asymptomatic restenosis and stent deformation was detected in 2 patients. Based on this experience, carotid stenting in high risk patients with severe coronary artery disease is feasible and safe and might be indicated as an alternative procedure for combined surgery.

Glial expression of cytokines in the brains of cerebrovascular disease patients.

We examined the immunohistochemical localization of the proinflammatory cytokines tumor necrosis factor-alpha, lymphotoxin and interferon-gamma in 22 autopsy brains of patients with either cerebrovascular disease (CVD) or other neurological diseases as well as 2 non-neurological control brains. These cytokines were coexpressed mostly in the microglia/macrophages and in a few astroglia in the brains with acute cerebral infarction and cerebral hemorrhage. In cases with cerebral infarction, they were observed as early as 33 h after the onset of the illness and persisted for up to 40 days after the onset. In one patient with cerebral hemorrhage who survived for 4 h, the cytokine-immunoreactive glial cells were confined to the margins of the hematoma. In contrast, the cytokine-immunoreactive glia were distributed diffusely in one patient with cerebral hemorrhage who died 12 days after the onset of the illness. Labeling for these cytokines was weak in the glial cells of control brains and those with neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and multiple system atrophy, in so far as there were no concomitant acute CVD foci. The present results indicate that proinflammatory cytokines are up-regulated in the brains of patients with acute stroke, and suggest an early inflammatory response in human CVD.