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High neutrophil to lymphocyte ratio (NLR) is correlated with the occurrence, morbidity and mortality of cerebrovascular disease as a marker of systemic inflammation. However, its effect on cerebral white matter hyperintensity (WMH) is unclear. We investigated high NLR burden as a surrogate marker of WMH volume in a healthy population. Healthy subjects with voluntary health check-ups between January 2006 and December 2013, including brain MRI and laboratory examination, were collected. WMH volumes were rated quantitatively. A total of 2875 subjects were enrolled, and the mean volume of WMH was 2.63 ± 6.26 mL. In multivariate linear regression analysis, NLR [β = 0.191, 95% confidence interval (CI) = 0.104 to 0.279, P < 0.001] remained significant after adjusting for confounders. Age (β = 0.049, 95% CI = 0.045 to 0.054, P < 0.001), hypertension (β = 0.191, 95% CI = 0.101 to 0.281, P < 0.001), diabetes (β = 0.153, 95% CI = 0.045 to 0.261, P = 0.006), and extracranial atherosclerosis (β = 0.348, 95% CI = 0.007 to 0.688, P = 0.045) were also significant independently from NLR. Additionally, the high NLR group (NLR ≥ 1.52) was related to male sex, hypertension, diabetes, current smoking, extracranial atherosclerosis, silent brain infarct, and high WMH volumes. In conclusion, high NLR is associated with larger WMH volumes in a healthy population. Assessment of NLR may be helpful in detecting cerebral WMH burdens in high risk groups. [ABSTRACT FROM AUTHOR]

Background Maladjustment of matrix metalloproteinases (MMPs) results in cerebral vasculature and blood–brain barrier dysfunction, which is associated with small vessel disease (SVD). This study was to aim at evaluating correlations between matrix metalloproteinase-2 and 9 single nucleotide polymorphisms and the risk of SVD. Methods A total of 178 patients with SVD were enrolled into this study via Nanjing Stroke Registry Program (NSRP) from January 2010 to November 2011. SVD patients were further subtyped as isolated lacunar infarction (ILI, absent or with mild leukoaraiosis) and ischemic leukoaraiosis (ILA, with moderate or severe leukoaraiosis) according to the Fazekas scale. 100 age- and gender-matched individuals from outpatient medical examination were recruited as the control group. The genotypes of MMP-2-1306 T/C and MMP-9-1562 C/T were determined by the TaqMan method. Results Of 178 SVD patients, 86 and 92 patients were classified as ILI and ILA, respectively. Comparison analysis between SVD patients and controls revealed a significant correlation between SVD and hypertension, as well as a prevalence of hypertension in ILA. Further genotype analysis showed that the frequency of MMP-2-1306 CC genotype was higher in ILA patients than in controls ( P = 0.009, χ 2 test; P = 0.027, the multiple test with Bonferroni correction). Finally, logistic regression analysis with adjustment of age, sex and vascular risk factors showed that the MMP-2-1306 T/C polymorphism was an independent predictor for ILA (OR: 2.605; 95% confidence interval [CI], 1.067–6.364; P = 0.036). Conclusion Our findings suggest that the MMP-2-1306 T/C polymorphism is a direct risk factor for ILA. [ABSTRACT FROM AUTHOR]

Abstract: Background: Asymmetric dimethylarginine (ADMA) has recently been investigated as a risk marker for cardio- and cerebrovascular diseases. However, whether ADMA levels are related to the risk of stroke in the Japanese general population remains unclear. Methods: We examined 769 Japanese men (mean age, 47±5years) undergoing health examinations. Each subject's ADMA level and various vascular risk factors were assessed; the predicted 10-year stroke risk was calculated using the point-based prediction model from the Japan Public Health Center Study. Results: In a multiple linear regression analysis, age, body mass index, estimated glomerular filtration rate, and current smoking status were significant independent determinants of ADMA levels. A significant odds ratio (OR) for high predicted stroke risk (10-year risk≥5%)was noted in the highest quartile of ADMA levels (OR, 2.47; 95% CI, 1.002–6.07), compared with the lowest quartile, after adjusting for potential confounding factors. A significant OR for high predicted stroke risk was also found for each standard deviation increment in ADMA level (adjusted OR, 1.46; 95% CI, 1.10–1.92). Conclusion: Elevated ADMA levels were significantly associated with an increased predicted stroke risk, suggesting that measuring ADMA levels may be useful for identifying middle-aged Japanese men with a high risk of stroke. [Copyright &y& Elsevier]

Abstract: Background: The vascular risk factors are associated with an increased risk for vascular cognitive decline (VCD), but also with Alzheimer disease (AD). Objective: To investigate vascular risk factors in relation to AD and VCD, with a non-invasive neurosonological methods in a clinical settings. Results: A total of 296 patients with AD and 237 patients with VCD were included in the study. Hypertension, hyperlipidemia, diabetes mellitus, stroke, and white matter changes (p<0.001) were significantly more prevalent in VCD, although they were also present in AD patients. No statistically significant differences were obtained between groups regarding coronary disease, atrial fibrillation, average degree of carotid artery stenosis and carotid intima-media thickness (cITM). However, the patients with AD had carotid artery stenosis “>50%” (p=0.007) and present plaques (p<0.001) more frequently compared to vascular group. The significant associations between robust cognitive measure and vascular factors, diabetes mellitus, carotid stenosis, cITM, and type of plaques were identified only in VCD, but not in AD group. Conclusions: The vascular risk factors were more prevalent in VCD group, although they were also present in AD. With few treatment options available in AD, it may be important not to neglect the vascular risk factors. [Copyright &y& Elsevier]

Abstract: Depression is frequently associated with Parkinson disease (PD) but neural basis is still unclear. In previous studies white matter changes present as signal hyperintesities on T2-wighted MRI studies (WMHs) commonly observed in older adults have been associated with depressive symptomatology. In this study we investigated whether WMHs were associated with depression in PD patients with disease onset above the age of 60. Thirty-four patients, with (PD-D) and 25 without depression (PD-nD), and 30 healthy age- and sex-matched controls were analyzed using the Scheltens visual rating scale. Cerebrovascular risk factors were similar across groups. Comparing controls and PD patients as a group there were no differences in WMHs in any examined regions. However, PD-D group had more common frontal WMHs although WMHs score didn''t rich statistical significance. The same came true for total deep white matter changes comparing those two groups. In addition PD-D group had a significantly higher score for periventricular regions WMHs comparing with both PD-nD group and controls.PD-D group had significantly higher WMHs scores BG regions when compared to controls. The only significance in multivariate analyses was shown for periventricular WMHs total score explaining the 39% of the variance in the depressive score. Our findings suggest that WMH in the deep white matter may contribute to depression in PD. [Copyright &y& Elsevier]

Abstract: Epidemiological studies show that vascular risk factors (e.g. atherosclerosis, diabetes, homocysteine, hypertension or cholesterol) may play a role in the development of Alzheimer''s disease. Animal models may help to discover the role of vascular risk factors on cognition. In the present project we treated male Sprague Dawley rats with a diet containing homocysteine (hyperhomocysteinemia) or cholesterol (hypercholesterolemia) for 5months or exposed the rats to ethanol (20% in drinking water) or a combination of cholesterol + ethanol (mix) for 12months. Our experiments show that all 3 treatments (homocysteine, cholesterol, ethanol) declined spatial memory in the 8-arm radial maze, reduced the number of cholinergic neurons and induced blood–brain barrier leakage in the cortex. Rats treated with cholesterol also displayed markedly enhanced inflammation in the cortex. Levels of amyloid precursor protein, beta-amyloid(1–42), as well as tau and phospho-tau 181 were significantly enhanced in the cortex of cholesterol-fed rats. A combination of ethanol and cholesterol did not further potentiate the effects on spatial memory, cholinergic neurons and blood–brain barrier leakage. The data suggest that chronic mild vascular risk factors over months induce small lesions of the brain capillaries in the cortex, which may contribute to the development of vascular dementia or also Alzheimer''s disease. [Copyright &y& Elsevier]

Abstract: Background: Kinase insert domain-containing receptor (KDR), vascular endothelial growth factor receptor-2, play a pivotal role in endothelial dysfunction, which may lead to silent brain infarction (SBI). We evaluated whether single nucleotide polymorphisms (SNPs) of KDR genes are associated with increased risk of SBI in a Korean population. Methods: A total of 383 patients with SBI and 387 controls were genotyped for the KDR −604T>C, 1192G>A, and 1719A>T SNPs. We separately analyzed this association according to the age (age≥65 and age<65) and the gender. We also compared haplotype frequencies between SBI patients and controls. Results: Genotype frequencies for three SNPs did not differ significantly between SBI patients and controls. In addition, haplotype analysis for three SNPs did not show a difference between patients and controls. However, the frequency of genotype of KDR −604T>C was significantly associated with an increased risk of SBI in the age<65years old group (AOR=1.515, 95% CI, 1.003 to 2.289, p=0.048) and in male group (AOR=1.596, 95% CI, 1.018 to 2.503, p=0.042). Conclusions: KDR −604T>C SNP may serve as genetic markers for the increased risk of SBI among the younger (<65years) or male only Korean subpopulations. [Copyright &y& Elsevier]

Abstract: Objectives: This study investigated the impact of smoking on the initial severity of acute ischemic stroke and examined its subsequent outcome. Methods: Patient data was collected from the Stroke Registry in the Chang Gung Healthcare System (SRICHS). A total of 2650 patients admitted for acute ischemic stroke from January to December 2009 were included. Baseline characteristics were compared between smokers and non-smokers. Factors affecting the initial severity and the recovery from neurological deficit were examined by logistic regression analysis. The patients were further divided according to stroke mechanism for subgroup analysis. Results: The total number of smokers and non-smokers was 817 (31.9%) and 1833 (69.1%), respectively. Univariate analysis showed that smokers had lower NIHSS scores on admission than did non-smokers (P <0.001). In subgroup analysis, smokers with small-vessel occlusions frequently had higher NIHSS scores on admission than did non-smokers (P =0.001). However, smokers with cardioembolic stroke had lower NIHSS scores on admission as compared to non-smokers (P =0.024). No subgroup had smoking as a significant factor for neurological recovery during hospitalization. Conclusions: Smoking correlated with higher NIHSS scores on admission for small-vessel occlusion. Conversely, it was associated with lower NIHSS scores on admission for cardioembolism. [Copyright &y& Elsevier]

Abstract: Background: The CHADS2 score is a stroke risk stratification system for patients with atrial fibrillation (AF). The relationship between the pre-admission CHADS2 score and stroke severity or outcome was examined in AF-related cardioembolic stroke patients. Methods: 423 consecutive AF-related cardioembolic stroke patients (250 men, 173 women; aged 76±10years) were reviewed. Results: Pre-admission CHADS2 scores of 0, 1, 2, 3, 4, 5, and 6 were present in 4.3%, 21.0%, 34.3%, 23.6%, 11.8%, 4.5%, and 0.5% of patients, respectively. There were significant correlations (P<0.001) between CHADS2 and National Institutes of Health Stroke Scale (NIHSS) scores on admission, and CHADS2 and modified Rankin scale (mRS) scores at discharge. The optimal cutoff CHADS2 score for an mRS score ≥3 was ≥2 (sensitivity 84%, specificity 38%). For death, the optimal cutoff CHADS2 score was ≥3 (sensitivity 59%, specificity 62%). On multivariate analysis, a CHADS2 score ≥2 was independently associated with an mRS score ≥3 (OR 1.93, 95% CI 1.39–2.72, P<0.001), and a CHADS2 score ≥3 was independently associated with death (OR 1.46, 95% CI 1.02–2.11, P=0.038). Conclusions: The CHADS2 score is related to severity and outcomes of stroke in patients with AF. [Copyright &y& Elsevier]

Abstract: Background: Chronic kidney disease (CKD) is associated with higher stroke incidence, but little is known about the impact of CKD on mortality during stroke hospitalization, especially by CKD stage and index stroke type. This study assessed the effect of prevalent CKD on risk of dying in the hospital after a stroke. Methods: Data were obtained from all US states that contributed to the Nationwide Inpatient Sample. All patients identified by the International Classification of Diseases, Ninth Revision procedure codes (n=1,127,842) admitted to hospitals between October 2005 and December 2006 with a discharge diagnosis of stroke were included. Independent associations of CKD with in-hospital mortality following stroke were evaluated using multivariable logistic regression. Results: Of the sample, 64,985 (6%) had CKD, of which 5,785 (9%) died in the hospital. In multivariable analyses, CKD was associated with mortality overall (OR 1.63, 95% CI=1.52–1.75) and regardless of stroke type: ischemic stroke (OR 1.70, 95% CI=1.55–1.86), subarachnoid hemorrhage (OR 1.93, 95% CI=1.45–2.58), intracerebral hemorrhage (OR 1.28, 95% CI=1.10–1.49). Association between CKD and greater mortality was more pronounced in younger age groups (CKD*age interaction: p<0.0001) and in women vs. men (CKD*sex interaction: p<0.0001). Higher CKD stage was associated with greater mortality odds, but only with Stages 5 (OR 3.21, 95% CI: 2.09–4.92) and 6 (OR 2.92, 95% CI: 2.62–3.25) was this association of significance. Conclusions: Presence of CKD is independently associated with higher odds of dying during stroke hospitalization regardless of index stroke type. This adverse association is driven by severe CKD and is more pronounced in relatively younger persons and women. [ABSTRACT FROM AUTHOR]

Abstract: Background: Data on the determinants and outcome of ischemic stroke (IS) from the Arabian Gulf countries (AGC) are still scanty. The aim of this study was to characterize IS in six large stroke centers on the Arabian peninsula. Methods: IS subtypes were evaluated in four AGC from January 2006 to December 2007 in a large prospective multicenter hospital-based stroke registry including demographics, baseline risk factors, outcome and management. Results: A total of 780 patients with IS were included. Mean age was 58.9years (63.7% males). Large-artery atherosclerosis (LAA) (38.1%) was the most common subtype followed by lacunar stroke (LS)(34.7%), cardioembolic stroke (CE)(13.5%) and other determined causes (7%). LAA and CE were both more commonly observed over the age of 70. LAA showed a higher male preponderance, and the highest prevalence of hypertension, diabetes, obesity and ischemic heart disease among all subtypes. Obesity was a risk factor for both LAA and CE. Anterior circulation stroke was significantly more affected in LAA (21.2%), CE (19%) and LS (15.1%) subtype of stroke than in posterior circulation strokes (4.4%, 2.9% and 2.8%, respectively) (p<0.05). Only 0.8% of patients received thrombolysis. The 90-day outcome was worst in LAA and least affected in LS. The over-all 90-day mortality was 2.1%. Conclusions: Demographically, our data are different from those in Western registries but the distribution of stroke subtypes is comparable. Compared to Asian registries the ratio LS versus LAA was much lower. For the first time these data allow to study the IS profile in this population. [Copyright &y& Elsevier]

Abstract: Background: Uric acid has been known to exert neuroprotective effects by acting as a free radical scavenger; however, several observational studies indicated that high levels of serum uric acid increased the risk of cardiovascular events or stroke. We sought to determine whether increased levels of uric acid are associated with the presence of silent brain infarction (SBI). Methods: We recruited a consecutive series of non-stroke individuals who visited the Healthcare System in our hospital and underwent brain MRI (n=1577). We conducted intensive interviews and laboratory examinations, including serum uric acid. We examined associations between SBI and vascular risk factors including uric acid by controlling possible confounders. Results: Of the 1577 subjects recruited, 921 were men and 656 were women, and the uric acid level was much higher in the men (6.3±1.3) than in the women (4.7±1.0). There was a strong dose–response relationship between the quartiles of uric acid and the presence of SBI in women (p =0.001), but not in men. Multivariable analysis showed that the highest quartile of uric acid level was an independent risk factor for the presence of SBI in total patients (adjusted OR, 1.79; 95% CI, 1.11–2.91). However, this association remained significant in women (adjusted OR, 2.64; 95% CI, 1.17–5.91), but not in men. Conclusions: Our results suggest that an increased level of uric acid may be a risk factor for the presence of SBI. Serum uric acid level might be a good serum marker of underlying SBI or future stroke, especially in women. [Copyright &y& Elsevier]

Abstract: Stroke is a complex disease caused by combination of multiple risk factors. Recent findings have suggested that stroke has a significant genetic component. Various types of genetic polymorphisms have been suggested to contribute to the risk of stroke. Gene polymorphisms of renin-angiontensin aldosterone system (RAAS) have been suggested to be risk factors for hypertension, cardiovascular diseases and stroke. In the present case–control study we investigated the association of −344C/T (rs179998) polymorphism in the promoter region of the human aldosterone (CYP11B2) gene with genetic predisposition to hypertension, ischemic stroke and stroke subtypes classified according to TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Four hundred and three stroke patients (hypertensives:normotensives=219:184) and three hundred and ninety four, sex and age matched healthy controls (hypertensives:normotensives=118:276) were involved in the study. The region of interest in the CYP11B2 gene was amplified by polymerase chain reaction and genotypes determined by subjecting the PCR products to restriction digestion by the enzyme HaeIII. Significant difference was observed in the genotypic distribution and allelic frequency between the stroke patients and healthy controls. TT genotype and T allele associated significantly with hypertension and stroke (p <0.000 in hypertension and p =0.000 in case of stroke). A stepwise logistic regression analysis confirmed these findings. To establish that this polymorphism is associated with stroke independent of hypertension, we compared stroke patients without hypertension with normotensive controls. Significant difference was observed in genotypic distribution and allelic frequency between the two groups (p =0.000). Further evaluating the association of this polymorphism with stroke subtypes we found significant associations with intracranial large artery atherosclerosis, lacunar stroke and cardioembolic stroke (p =0.000 in each case). In conclusion our study suggests that −344T allele of CYP11B2 gene is an important risk factor for hypertension and ischemic stroke. However, this is a preliminary study and the results need to be confirmed in a larger cohort. [Copyright &y& Elsevier]

Abstract: In order to evaluate progress in preventive therapeutic strategies, and to identify potential targets for improvement, it is essential to assess changes in the risk factors and preventive treatment of stroke over time. All of the strokes occurring within the population of Dijon, France (150,000 inhabitants), were prospectively ascertained from 1985 to 2004. Changes in stroke risk factors and preventive medications were analyzed by stroke subtypes. We recorded 725 lacunar infarcts (LI), 497 cardioembolic (CE) strokes, 2054 ischemic stroke from atheroma of large arteries or from other and undetermined causes (OIS), and 341 primary cerebral haemorrhages (PCH). Over the 20years, the prevalence of hypercholesterolemia increased whatever the stroke subtype (p <0.01) whereas that of diabetes only rose in LI and OIS stroke. The proportion of stroke patients on antiplatelet agents increased overall (p <0.01) and the proportion of patients on anticoagulants rose in CE stroke (p =0.01) and PCH (p <0.01). The proportion of patients on antihypertensive treatment only increased in CE stroke (p =0.01). The risk factor profile and the preventive treatments in stroke patients showed divergent variations over the 20years, according to the stroke subtype considered. These modifications certainly reflect changes in the therapeutic strategies for the preventive management of the population at risk. [Copyright &y& Elsevier]

Abstract: Stroke is the third largest cause of death and a major cause of adult disability and mortality worldwide. Experimental evidence suggests that genetic determinants do contribute a large part to stroke risk. The identification of phosphodiesterase 4D gene as a risk factor for stroke caused a great deal of interest in stroke genetics. Many of the studies of PDE4D gene have focused on the original Icelandic findings but the association between specific SNPs and haplotypes has been inconsistent. The aim of the present study was to investigate the association of three SNPs 32 (rs 456009), 83 (rs 966221) and 87 (rs 2910829), originally described by deCODE group; with stroke in a South Indian population from Andhra Pradesh. Two hundred and fifty ischemic stroke patients and two hundred and fifty controls were included in the study. The stroke patients were sub typed according to TOAST classification. SNP 83 showed significant association with stroke in the population under study while SNPs 87 and 32 were monomorphic. Further SNP 83 was found to be significantly associated with two stroke subtypes, intracranial large artery atherosclerosis (the most frequent subtype in the population) and small artery occlusion. The association with other subtypes was found to be insignificant. Further, SNP 83 was found to be associated significantly with some conventional stroke risk factors like diabetes and smoking. [Copyright &y& Elsevier]

Abstract: Background: The aims of this study were to clarify the risk factors for stroke, and to investigate the effect of low-density lipoprotein cholesterol (LDL-C) lowering with pravastatin on the risk of stroke, in Japanese mild-to-moderately hypercholesterolemic patients enrolled in the MEGA Study. Methods: Multivariate Cox proportional hazard model was used to determine the baseline risk factors for stroke. The proportion of treatment effect (PTE) explained by on-treatment LDL-C levels was estimated. Results: In 7832 patients at risk, a total of 99 strokes were observed during the 5-year follow-up period. Significant relationships were observed between stroke and traditional risk factors such as male sex, advanced age, low high-density lipoprotein cholesterol (HDL-C), high lipoprotein(a) (Lp[a]), hypertension, diabetes, obesity, and smoking. In the pravastatin group, hazard ratio (HR) for stroke adjusted by on-treatment lipid level was lower than the unadjusted value versus control (HR [95%CI], 0.48 [0.26–0.87] and 0.59 [0.38–0.92], respectively)—giving a negative PTE of −38.6% and suggesting that the risk reduction could not be explained by LDL-C lowering alone. Conclusions: Male sex, aging, hypertension, diabetes, low HDL-C, high Lp(a), obesity, and smoking were determined as risk factors for stroke in Japanese patients with hypercholesterolemia, and the observed risk reduction could not be explained by pravastatin''s LDL-C-lowering effect alone, suggesting pleiotropic effects. [Copyright &y& Elsevier]

Abstract: Background: Vascular localization of symptomatic large artery atherosclerotic (LAA) stroke differs for unknown reasons by race-ethnicity. The metabolic syndrome (MetSD) is associated with higher atherosclerotic stroke risk and comprises abnormal risk factors that can vary by race. Thus, we investigated whether MetSD may contribute to race-ethnic differences in LAA stroke by examining the association of MetSD with symptomatic intra- and extracranial atherosclerosis among a diverse race-ethnic group. Method: We analyzed data prospectively collected over a 4-year period on subjects with ischemic stroke/TIA. Independent vascular risk factor associations with intracranial and extracranial LAA vs. non-LAA mechanism were evaluated in two groups stratified by race-ethnicity; whites and non-whites (Hispanics, African-American, and Asian-American). Results: 1167 patients met study criteria. Intracranial LAA was more prevalent in non-whites vs. whites (20.4% vs. 9.6%, P <0.001), while extracranial LAA had a more frequent point value in whites compared to non-whites (10.7% vs. 7.5%, P =0.267). The presence of MetSD was more prevalent in both intracranial and extracranial LAA group than in non-LAA group: no significant differences were observed in the prevalence of MetSD between intra vs. extracranial LAA or whites vs. non-whites. However, with increasing numbers of abnormal metabolic components, whites were more likely to have experienced extracranial LAA, whereas non-whites were more likely to have experienced intracranial LAA. After adjusting for covariates, MetSD was associated with extracranial LAA in whites (OR, 1.98; 95% CI, 1.13–3.45), while there was a tendency that intracranial LAA was associated with MetSD in non-whites (OR, 1.80; 95% CI, 0.97–3.32). No association was found between MetSD and extracranial LAA in non-whites and between this syndrome with intracranial LAA in whites. Conclusions: Our results showed that the impact of MetSD on the distribution of cervicocephalic atherosclerosis differed by race-ethnicity. This finding may in part explain the well-known differences in race-ethnic predilection to intracranial or extracranial atherosclerosis. [Copyright &y& Elsevier]

Abstract: Current data concerning the association between family history and the risk for developing stroke have been controversial. There has been very little data on the influence of family history on intracranial atherosclerosis (ICAS), stroke severity, and recovery, especially among Asian populations. We evaluated the association between family history and the risk for stroke and investigated the relationships between family history and ICAS, stroke severity, and short-term stroke outcome in Korean stroke patients. In this case–control study, we recruited 400 patients with acute ischemic stroke, along with the same number of age- and gender-matched control subjects. Assessments of first-degree family history of stroke, myocardial infarction, hypertension and diabetes mellitus were obtained by structured questionnaires, followed by reviews of the clinical and neuro-radiological findings of the stroke patients. A family history of stroke was associated with an increased risk of ischemic stroke (OR, 2.65; 95% CI, 1.75 to 4.01), and the correlation remained significant after multivariate analysis. The odds ratios of paternal, maternal, and sibling history were 2.07, 2.16, and 4.21, respectively. The risk of stroke did not differ significantly with the presence of ICAS, stroke severity, and stroke outcome. Family history of stroke was an independent risk factor for ischemic stroke. A positive sibling history was more strongly correlated with the incidence of stroke than a positive parental history, and this finding may indicate the possible role of environmental factors in a shared household in addition to the genetic factors involved in family medical history. [Copyright &y& Elsevier]

Abstract: Background: Brain images of patients with Alzheimer''s disease (AD) on magnetic resonance imaging (MRI) show white matter lesions (WML), which are attributed to degenerative changes of small vessels. These lesions are supposed to be among the factors supporting the diagnosis of probable AD; however their correlation with the severity of dementia requires further studies. Methods: We examined four groups of patients with cognitive impairment: Ten patients with amnestic-MCI (Mild Cognitive Impairment), 11 with mild AD (21–24 points in MMSE), 17 with moderate AD (11–20 points in MMSE) and 15 with severe AD (3–10 points in MMSE). The T2 and FLAIR MRI sequences of the brain of each patient were assessed using the White Matter Lesions Semiquantitive Rating Scale, taking into consideration the amount, size and distribution of WML. Results: WML of the brain were seen in almost all patients with AD and MCI on T2 and FLAIR sequences. The positive correlation between the patients'' age and the amount and size of WML, in subcortical (T2: p <0.01, r =0.39; FLAIR: p <0.05, r =0.31) and in the periventricular region (T2: p <0.05, r =0.28; FLAIR: p <0.05, r =0.35) has been shown on both sequences. There was no correlation between the size or distribution of lesions and either hypertension or homocysteine blood level. The analysis revealed also that in both sequences, the severity of lesions in the periventricular region increased with the progression of the disease (T2: p =0.038; FLAIR: p =0.02). Conclusions: A significant factor correlating with the location of WML in patients with MCI and AD is the age of patient. The amount and size of WML in the periventricular and subcortical regions of the brain correlates with the severity of dementia. Hypertension and hyperhomocysteinemia have no influence on the presence of described lesions. [Copyright &y& Elsevier]

Abstract: Background and purpose: Apolipoprotein E (apoE) polymorphism is suggested to be a risk factor in stroke in some populations, either by affecting lipid parameters or independently. Its effect on lipoprotein(a) [Lp(a)] is not known. The roles of apoE polymorphism and of high Lp(a) levels in atherosclerotic stroke (AS) in the Turkish population are unclear. Our aim was to investigate the relationship of apoE alleles and Lp(a) level with AS and the relationship of apoE alleles with Lp(a) and other lipid parameters. Methods: ApoE polymorphisms and lipid parameters were prospectively evaluated in 85 patients and 77 controls with normal brain imaging. Results: Only hypertension, diabetes mellitus, associated vascular diseases and decreased high-density lipoprotein cholesterol levels were found to be independent risk factors for stroke. However, in the presence of apoE/E4 allele, increased low-density lipoprotein cholesterol (LDL-chol), apolipoprotein B (apoB) and Lp(a) levels and in the presence of apo E/E3 allele, only Lp(a) levels were determined as risk factors. Conclusion: This study showed that while apoE polymorphism was not a risk factor itself, high Lp(a), LDL-chol and apoB were determined to be risk factors in E3 or E4 carriers. [Copyright &y& Elsevier]

Abstract: Background: Ischemic stroke is the end phenotype of a complex interaction between various genetic and environmental factors. Objective: We aimed to explore association of two lipid-relevant genetic variants and conventional risk factors with risk of having ischemic stroke in Northern Han Chinese. Methods: Genotyping was performed in 396 ischemic stroke patients and 396 controls that were all recruited from the four hospitals of Qiqihar city. Data were analyzed using χ 2 test, logistic regression and haplotype analyses. Results: Significant differences were observed for genotype and allele distributions of APOE ε2/ε3/ε4 polymorphism (P <0.001) with ε4 allele conferring a 2.19-fold risky effect (P <0.001), while no statistical differences were found for LDLR C1773T distributions. Haplotype analysis indicated the remarkable differences for haplotypes harboring APOE “ε2” or “ε4” alleles between cases and controls after the stringent Bonferroni correction. Moreover, all multiple-testing associations remained significant using false discovery rate (FDR) method. Further our multiple logistic regression analysis showed significant associations of hypertension status (OR=5.37, P <0.001) and APOE ε2 (OR=0.45, P <0.001) and ε4 (OR=1.50, P =0.003) alleles with ischemic stroke after controlling confounders, and their correlations with plasma lipid profiles were strengthened by stratification of alleles and hypertension status combined. Conclusions: Our results not only demonstrated potential interactions of APOE ε2/ε3/ε4 and LDLR C1773T polymorphisms with risk of having ischemic stroke, but also added the evidence of independent role of hypertension and APOE ε2/ε3/ε4 polymorphism in the development of this disorder in Northern Han Chinese. [Copyright &y& Elsevier]

Abstract: Background: There are conflicting data on the relationship between peripheral arterial disease (PAD) as defined by an ankle–brachial index (ABI) of <0.9 and stroke risk, and these prior data have largely focused on a single race or gender. Furthermore, the association between subsequent ABIs above the established 0.9 threshold for PAD vs. stroke has not been studied. This study assessed stroke occurrence across the full spectrum of ABI values among a broad cohort of stroke survivors. Methods: Data from the National Health and Nutrition Examination Survey from 1999–2004, a nationally representative sample of United States adults, were used to assess prevalence of PAD as evidenced by ABI of <0.9, and to simultaneously identify the independent associations of ABI levels (<0.90, 0.90–0.99, 1.00–1.09, >1.3) with stroke prevalence. Results: Among 6382 adults, 4602 (72%) had full and complete data of which 277 (6%) reported stroke occurrence. Stroke survivors were older and more likely to have diabetes, hypertension, coronary artery disease, elevated blood pressure and glycohemoglobin, than non-stroke respondents. More subjects with ABI <0.9 vs. ≥0.9 had experienced a stroke (12.7% vs. 5.4%, p<0.001). Within the full ABI range, stroke presence rose with decreasing ABI (p =0.0013). After adjustment for potential confounders, only ABI <0.9 (OR 1.9, 95% CI=1.2–3.1) and 0.9–0.99 (OR 2.3, 95% CI=1.4–3.6) compared with the referent group (1.10–1.29) were significantly associated with presence of stroke. Conclusions: Data from this nationally representative cohort support an independent relationship between established PAD and stroke occurrence, but also indicate that even borderline PAD is strongly linked to stroke. [Copyright &y& Elsevier]

Abstract: Background: Although several risk factors for stroke have been reported in patients with atrial fibrillation (AF), the relation of LV diastolic dysfunction to stroke is still uncertain in these patients. We evaluated the relationship between tissue Doppler-derived index, E/E'', as well as other clinical and echocardiographic parameters and ischemic stroke by this cross-sectional study. Methods: Three hundred thirty patients with persistent AF who had preserved LV ejection fraction were included from 6 centers. Clinical data were obtained and standard transthoracic echocardiography was performed. Patients without a history of ischemic stroke (n =280) were compared with patients with this complication (n =50). Potential determinants of ischemic stroke were identified by logistic regression analyses. Results: In univariate analyses, age, history of hypertension, diabetes mellitus, hyperlipidemia and symptomatic heart failure, plasma brain natriuretic peptide (BNP) level, early mitral inflow velocity (E), diastolic mitral annular velocity (E''), and E/E'' ratio were significantly correlated to ischemic stroke. Multivariate regression analyses identified two significant variables that were independently associated with ischemic stroke: hypertension (odds ratio=6.03, p =0.008), and E/E'' (odds ratio=1.21, p =0.002). Conclusions: These findings may have clinical implications that LV diastolic dysfunction, reflected by E/E'', is a significant determinant of ischemic stroke in AF. A larger prospective data is needed to confirm the value of E/E'' in risk stratification for ischemic stroke in this population. [Copyright &y& Elsevier]

Background: The fact that the allele &epsiv;4 of the Apolipoprotein E (APOE) gene could act like a risk factor not only in late-onset familial and sporadic Alzheimer''s disease (AD) but also in cerebrovascular disease (CVD) and vascular dementia (VaD) is still controversial. Methods: In order to study if &epsiv;4 allele is overrepresented not only in AD but also in CVD and VaD, APOE genotyping was undertaken in a series of 247 patients: 26 cases with VaD, 41 cases with CVD but without cognitive impairment (CVD-C), 83 cases with AD and 97 aged-matched “healthy controls” (HC). Results: Percentages of subjects bearing one or two copies of the &epsiv;4 allele was much higher in AD patients (54%) than in either CVD-C (29%) (p<0.05), VaD (15%) (p<0.001) or HC (13%) (p<0.001). Conclusions: These results strengthen the hypothesis that involves the APOE &epsiv;4 allele as a predisposing factor for AD, but not for CVD or VaD. [Copyright &y& Elsevier]

Hypertension is a risk factor for stroke and may also contribute to the development of vascular cognitive impairment (VCI) and vascular dementia (VaD). Cognitive complications of hypertension and the influence of anti-hypertensive treatment were underestimated until recently. In this paper, trials investigating the effect of anti-hypertensive treatment on cognitive function were evaluated. Analysis of these studies revealed that until approximately 1990–1995 investigations have assessed primarily if anti-hypertensive treatment impaired cognitive function. Only more recent studies have investigated positive effects on cognition of anti-hypertensive medication. Drugs more extensively evaluated were diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, sartanes and Ca2+ channel blockers. Available studies have confirmed that elevated diastolic blood pressure or pulse pressure and isolated systolic hypertension play an important role in the development of cognitive impairment. Randomized placebo-controlled trials have provided evidence that reduction of hypertension safely and effectively decreases morbidity and mortality rates and cognitive complications of hypertension. Ca2+ channel blockers and ACE inhibitors have been shown to be effective and probably better than diuretics and beta-blockers on cognitive domains of hypertension. More extensive investigations could contribute to establishing optimal choice and drug dosage for the treatment of cognitive complications of hypertension. [Copyright &y& Elsevier]

Background: Vascular dementia (VaD) is occasionally caused by a single, strategically located stroke. In this report, we describe the clinical and anatomical features of 12 cases of strategic single infarct dementia (SSID) from Singapore. Methods: Each patient completed a standardized diagnostic evaluation including history, neurological and neuropsychological examination, laboratory testing, and brain imaging. Dementia was diagnosed using the Diagnostic and Statistical Manual, 3rd edition, revised (DSM-III-R) criteria, and VaD was diagnosed using the National Institute of Neurologic Disorders and Stroke and the Association Internationale pour la Recherche et l''Enseignement en Neurosciences (NINDS–AIREN) criteria. VaD patients whose brain imaging study revealed a single cerebrovascular event were diagnosed with SSID. Results: We identified 12 cases of SSID among 125 VaD patients (9.6%). Stroke mechanism was lacunar infarction in five cases, embolism in four cases, large vessel thrombosis in two cases, and parenchymal hemorrhage in one case. The most commonly impaired cognitive domains on neuropsychological testing were visual memory, visuoconstruction, and language. In 11 of the 12 SSID cases, the stroke was located in the left hemisphere. The thalamus, either alone or as the proximal portion of a posterior cerebral artery infarction, was involved in 8 of the 12 cases. Stroke locations in the nonthalamic SSID cases included left angular gyrus, subcortical left frontal lobe including minor forceps, left basal forebrain and medial frontal lobe plus anterior corpus callosum (proximal anterior cerebral artery infarction), and anterior corpus callosum alone. Conclusions: Various stroke mechanisms may produce SSID. In our SSID cases, vascular damage almost always involved the left hemisphere and frequently involved the thalamus and major interhemispheric or intrahemispheric white matter pathways. [Copyright &y& Elsevier]

Mutations in NOTCH3 are the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) an inherited small vessel disease leading to subcortical strokes and dementia. Since the vascular pathology is clearly defined, CADASIL may provide important insights into the mechanisms underlying lacunar infarcts, ischemic white matter changes, and vascular dementia. Evidence from different sources suggests a central role for vascular smooth muscle cells (VSMC) in the pathophysiology of the disease. This article gives a brief overview on the phenotypic spectrum of the disease and discusses some of the relevant disease mechanisms that lead from Notch3 mutations to ischemic infarcts. [Copyright &y& Elsevier]

The existence of vascular dementia (VaD) was first identified by Marie, who described the etat lacunaire, and by Binswanger, who identified white matter lesions in demented individuals. The role of cortical lesions, while clear to clinicians, was highlighted only later by the pathological studies of Tomlinson and the clinical demonstrations of Hachinski et al., who have defined multi-infarct dementia. Lately, the emphasis shifted to pathogenic mechanisms with the identification of a multitude of processes, such as lipohyalinosis, cardiac dysfunction and genetic causes, to name only a few. Epidemiologic studies have demonstrated the high frequency of VaD, as well as the fact that vascular factors can contribute to Alzheimer''s disease (AD). All these considerations converge to the realization that VaD is an extremely important clinical entity and that its prevention and treatment are within reach. In fact, there is more data on how to prevent strokes (and presumably VaD) than on how to prevent AD. Moreover, many factors which were identified as contributing to cerebrovascular disease in general and VaD in particular are frequently suspected as predisposing to AD as well. These unexpected findings highlight the importance of mixed vascular-degenerative dementia as a disorder which has to be properly defined and has important implications on prevention and treatment. [Copyright &y& Elsevier]

Many studies have provided data showing that family history of stroke (FHS) is associated with an increased risk of stroke. The association of the FHS with the various stroke subtypes has not been adequately studied. The purpose of this study was to assess the association of the FHS with the two major stroke types (cerebral haematomas and ischaemic strokes) and the four stroke subtypes (cardioembolic, large artery disease, small artery disease, and undetermined) in a Greek population.The FHS was obtained from 421 consecutive acute stroke patients and from 239 matched control subjects. Positive FHS was observed in 49% of all stroke patients compared with 28% of the control subjects [adjusted OR=2.06 (95% confidence intervals (CI) 1.42–3.00)]. Haematomas, ischaemic strokes, and from the ischaemic strokes, both large and small artery disease strokes were strongly associated with positive FHS compared with the control subjects [adjusted OR=2.06 (95% CI 9–3.04), 2.07 (95% CI 1.09–3.91), 2.05 (95% CI 1.24–3.38), and 2.76 (95% CI 1.55–4.91), respectively]. There was no difference between maternal and paternal heritable contribution.In conclusion, FHS was found in this study to be an independent risk factor for all strokes combined, for each stroke type, and for the large and small-artery disease stroke subtypes, but not for the cardioembolic and undetermined stroke subtypes. [Copyright &y& Elsevier]

Abstract: Background and purpose: Stroke risk of asymptomatic atherosclerotic middle cerebral artery (MCA) stenosis has not been well studied. This study was designed to investigate stroke risk and prognostic factors of asymptomatic atherosclerotic MCA stenosis. Materials and methods: A total of 200 consecutive patients who visited the transcranial Doppler ultrasound (TCD) laboratory of our hospital and who met the following criteria were prospectively enrolled in this study: diagnosed as MCA stenosis due to atherosclerosis by TCD, age above 40years old, no history of ischemic stroke or transient ischemic attack (TIA), no ipsilateral carotid artery stenosis. The mean follow-up time was 38.3±9.9 (range 4 to 60) months. Results: Thirteen patients were lost to follow up. Seven patients (3.8%) developed ischemic stroke or TIA during the follow-up period, with an occurrence rate of 0.5% in the first year and 1.6% in the second year. Three were in the blood supply region of diseased vessels, three were in the contralateral hemisphere and one case of TIA occurred in the posterior circulation. Univariate analysis showed that diabetes mellitus (DM) (X2 =9.168, p=0.002) and carotid atherosclerotic plaque (X2 =4.403, p=0.036) were associated with higher risk of stroke occurrence in this cohort. Conclusions: The stroke risk in patients with asymptomatic atherosclerotic MCA stenosis was low and remained stable during follow up. Higher risk of stroke occurrence is associated with DM and carotid atherosclerotic plaque. [ABSTRACT FROM AUTHOR]

Abstract: An association between migraine and ischemic stroke has been observed for many years but exact mechanisms by which migraine can lead to stroke are currently still under investigation. Migraine is related to stroke in several ways. First, ischemic stroke can develop as a complication of an attack of migraine with aura (so called migraineous infarction). Second, epidemiological studies suggest that migraine with aura is a risk factor for ischemic stroke. Third, a patent foramen ovale (PFO) is a well known risk factor for stroke and on the other hand, seems to be associated with migraine with aura. The purpose of this review is to summarize the current literature linking the two neurological diseases: migraine and stroke. For many years, migraine and cerebral ischemic stroke have been linked together. The association between these two diseases is multidimensional and rather complex. [ABSTRACT FROM AUTHOR]

Abstract: The frequency and risk factors for intracerebral haemorrhage (ICH) after ischemic stroke are well-known. ICH frequency is increased by the use of antithrombotic or thrombolytic drugs. Several experimental studies have demonstrated a relationship between ICH and hypertension after fibrinolysis, but the optimal blood pressure levels in patients treated with recombinant tissue plasminogen activator (rTPA) are as yet unknown. We evaluated the role of blood pressure in patients with ischemic stroke treated with rTPA within 3h of symptom onset. We treated 86 consecutive patients admitted to our stroke unit between 2002 and 2008 and prospectively recorded the clinical and instrumental data in our stroke registry. We evaluated haemorrhagic complications by reviewing imaging findings. Blood pressure was recorded before rTPA and at 6, 12, 18, and 32h. Total cerebral haemorrhage occurred in eleven (12.7%) patients, and symptomatic intracerebral haemorrhage occurred in seven (8.1%). We failed to find a correlation between blood pressure levels and stroke severity at admission. High blood pressure levels correlated with a worse outcome. Systolic blood pressure was significantly higher in ICH patients relative to rTPA-treated patients without haemorrhagic complications (p<0.03). This study indicates that rTPA-induced haemorrhage is influenced by systolic blood pressure. More aggressive pharmacological reduction of hypertension during fibrinolysis and the subsequent 32h may reduce this complication. [Copyright &y& Elsevier]

Abstract: Objective: To evaluate the role of ACT gene polymorphism in primary spontaneous intracerebral hemorrhage (PSICH) and ischemic stroke (IS). Methods: 193 PSICH, 272 IS and 188 controls were included from the same geographical area. The demographic and clinical stroke risk factors were noted. PSICH was confirmed by CT and IS by MRI. The location of stroke and size were noted. ACT gene polymorphism was analyzed by polymerase chain reaction. The ACT genotype and allele frequency in PSICH, IS and controls were compared. Results: The age of the PSICH was 56.9±13years, IS 54±16.7years and controls 54.8±10years. 134 females were in study and 65 in control groups. In the controls the AA genotype was 30%, AT 51.1% and TT in 16% whereas these were 39.3%, 53% and 7.7% in PSICH and 34.6%, 53.3% and 12.1% in IS. The frequency of T allele in controls was 41.5%, PSICH 34.2% and IS 38.6%. There was no significant difference in genotype and allele frequency in PSICH, IS and controls as well as location and etiology of stroke. Interpretation: The ACT genotype and allele frequency are not different in Indian PSICH and IS compared to controls. [Copyright &y& Elsevier]

Abstract: Migraine is an independent risk factor for ischemic stroke, mainly in the subpopulation of women with migraine with aura who are younger than 45 years, particularly those that use estrogen containing oral contraceptives. Migraine however should be considered a benign condition as the absolute increase of stroke risk is small. Migraine is also associated with a high prevalence of cerebral white matter hyperintensities, occurring in the deep and periventricular white matter as well as infratentorial, mainly pontine. The pathogenesis and clinical significance of these hyperintensities is unclear. We do not know whether migraine may be considered a progressive disorder in a subset of patients because of accumulation of these hyperintensities over time. Studies on the relationship between migraine and cognitive functioning yielded conflicting results. Two recent studies have provided reassuring news for the migraine patient. A population-based twin study showed that a lifetime migraine diagnosis was not associated with cognitive deficits in middle-aged subjects. A long-term prospective study, assessing cognitive and memory changes in ageing individuals with and without a history of migraine, showed that migraineurs do not exhibit more decline on cognitive tests over time versus controls. Migraine is certainly not a recognized risk factor for (vascular) dementia. [Copyright &y& Elsevier]

Abstract: Arterial beta stiffness index is a potential risk factor for increased stroke occurrence. Vascular component appears to be significant in both Alzheimer''s disease (AD) and vascular dementia (VAD). We aimed to further explore vascular characteristics of patients with both types of cognitive decline using non-invasive neurosonological methods. There were 38 patients; 16 diagnosed with AD and 22 with VAD. Vascular risk factors were assessed and ultrasound measurements on common carotid artery (CCA) were performed using Aloka ProSound ALPHA 10 with 13 MHz linear probe. Among AD patients there were 5 with arterial hypertension (AH), 3 with atrial fibrillation (AF), 2 with diabetes mellitus (DM), 6 with hyper lipidemia and 1 smoker. Nineteen VAD patients had AH, 6 had AF, 12 had hyper lipidemia and one was diabetic. We found no statistically significant differences between groups regarding average body mass index (BMI), blood pressure, pulse pressure, intima–media thickness (IMT), CCA diameter or arterial beta stiffness indices. However, the trend of BMI increase, slight blood and pulse pressure decrease, CCA diameter increase and beta stiffness index increase was noted in VAD patients. Even though there was no significant difference found among two explored subgroups of patients with dementia, there was a tendency of greater systolic and diastolic diameters noted in VAD as well as greater stiffness, especially when measured in the right CCA. This indicates that VAD patients may have more prominent vascular changes that may help differentiate the type of dementia and further monitor these individuals. Further studies on a larger number of patients are needed support this evidence. [Copyright &y& Elsevier]

Abstract: Background and purpose: Congestive heart failure is a risk factor for ischemic stroke. Brain natriuretic peptide (BNP) is used as a biological marker of heart failure. We hypothesized that heart failure was associated with the onset of ischemic stroke patients with atrial fibrillation (AF). Methods: Between June 2006 and December 2007, we prospectively enrolled consecutive acute ischemic stroke patients with AF within 24 h of onset. Plasma BNP was measured twice, on admission and on days 28 or at discharge. As a control, we measured plasma BNP of chronic phase of stroke outpatients with AF. We investigated whether plasma BNP was elevated in the acute phase of stroke. Results: One hundred and nine patients (58 females; mean age, 76.3 years) were enrolled in the present study. Mean±SD of NIHSS score on admission and mRS score at discharge were 12.6±8.3 and 3.7±1.8, respectively. The interval from stroke onset to plasma BNP measurement on admission was 6.8±6.3 h. Moreover, follow up BNP was measured at mean of 26±9 days after stroke onset. The plasma BNP level in the acute phase of stroke was significantly higher than that of the subacute phase of stroke (median (interquartile range, IQR) 299.0 (176.8–469.5) vs. 149.5 (68.1–347.0) pg/ml, p <0.001). There was no significant difference in plasma BNP level between the subacute phase of stroke and control group (median (IQR) 149.5 (68.1–347.0) vs. 165.0 (64.6–224.0) pg/ml, p =0.543). Conclusion: Plasma BNP was elevated in the acute phase of stroke. Heart failure may be associated with the onset of ischemic stroke patients with AF. [Copyright &y& Elsevier]

Abstract: Several reports describe a potential association between prolonged flights and stroke. However, causes of travel-related stroke due to paradoxal embolism other than patent foramen ovale have not been previously reported. We here describe the case of a 44-year-old woman who presented with an acute anterior circulation stroke after a transoceanic flight. The patient received intravenous thrombolytic therapy, with complete recanalization of the anterior and middle cerebral arteries. Contrast transthoracic echocardiography was suggestive of an extracardiac right-to-left shunt. Both cardiothoracic CT and MR angiography revealed a single pulmonary arteriovenous malformation (PAVM) in the lower lobe of the right lung. No cardiac abnormalities were identified. Careful examination of the patient revealed telangiectatic skin lesions, and recurrent epistaxis was reported to occur in first-grade relatives. Genetic testing for hereditary haemorrhagic telangiectasia revealed no mutations in the endoglin and activin receptor-like kinase 1 genes. Intravascular embolization of the PAVM was performed and effective occlusion was later confirmed. To our knowledge, this is the first reported case of travel-related stroke associated with a PAVM. These should be considered in patients with stroke after prolonged flights, particularly when right-to-left shunt is detected and patent foramen ovale is ruled out. [Copyright &y& Elsevier]