Jae-Sung Lim

The correlation between cerebral arterial pulsatility and cognitive dysfunction in Alzheimer's disease patients

BACKGROUND Potential role of vascular dysfunction has been suggested in the pathogenesis of Alzheimers disease (AD). Previous cross-sectional studies have demonstrated relations between abnormal transcranial Doppler (TCD) parameters and cognitive impairment. We aimed to investigate the associations between longitudinal changes of TCD parameters and cognitive decline in patients with AD. METHODS We have enrolled patients with mild to moderate AD who aged 60 to 79years. Mean flow velocity and pulsatility index (PI) of anterior (ACA), middle (MCA), and posterior (PCA) cerebral arteries were evaluated. Cognitive functions were assessed using mini-mental state examination (MMSE), clinical dementia rating sum of boxes (SOB), and Alzheimers Disease Assessment Scale (ADAS-cog), which was further categorized as praxis, language, and memory subscores. TCD and cognitive assessments were followed up 1year later, and the longitudinal changes (Δ) between the baseline and follow-up measurements were evaluated. RESULTS A total of 51 patients completed the follow-up evaluations (baseline age 71.5years, MMSE 21.2). In the baseline evaluations, high PI values of ACA and MCA were associated with poor MMSE score, ADAS-cog total, memory, and praxis subscores. After 1year, the increases of ACA and MCA PI were correlated with the aggravation of ADAS language subscore, and ΔACA PI was also correlated with ΔSOB. The decrease in mean flow velocity of ACA was associated with aggravation of ADAS-cog praxis score. CONCLUSIONS There was significant correlation between longitudinal changes of TCD parameters and cognitive dysfunction in patients with mild to moderate AD. Serial assessment of TCD may provide useful information regarding to the disease progression.

Effects of Temperature and Pressure on Acute Stroke Incidence Assessed Using a Korean Nationwide Insurance Database

Background and Purpose Many studies have evaluated the association between weather and stroke, with variable conclusions. Herein we determined the relationships between daily meteorological parameters and acute stroke incidence in South Korea. Methods Patients with acute stroke (2,894) were identified by standard sampling of a nationwide insurance claims database from January to December 2011. We used multiple Poisson regression analyses of stroke incidence and meteorological parameters (mean temperature, diurnal temperature change, temperature differences over the preceding 24 hours, atmospheric pressure, humidity, wind speed, and physiologically equivalent temperature) to calculate the relative risk of stroke incidence associated with meteorological parameters. Results There were no seasonal variations in the incidences of ischemic (2,176) or hemorrhagic (718) stroke. Temperature change during the day was positively correlated with ischemic stroke in men (relative risk [RR] 1.027; 95% confidence interval [CI] 1.006–1.05) and older patients (≥65 years) (RR 1.031, 95% CI 1.011–1.052). Temperature differences over the preceding 24 hours had a negative correlation with all strokes (RR 0.968, 95% CI 0.941–0.996), especially among older women. Diurnal variation of atmospheric pressure was also significantly associated with the incidence of ischemic stroke (age<65 years, RR 1.051, 95% CI 1.011–1.092; age≥65 years, RR 0.966, 95% CI 0.936–0.997). Conclusions Diurnal temperature change, temperature differences over the preceding 24 hours, and diurnal variation of atmospheric pressure were associated with daily stroke incidence. These findings may enhance our understanding of the relationship between stroke and weather.

Distal hyperintense vessel sign is associated with neurological deterioration in acute ischaemic stroke

The aim was to evaluate the relationship between distal hyperintense vessel sign (HVS) and early neurological deterioration (END) in acute ischaemic stroke with large vessel steno‐occlusion.

Clinical relevance of abnormal neuroimaging findings and long‐term risk of stroke recurrence

Previous studies have revealed that the predictors of short‐ and long‐term stroke recurrence are different. We designed a comprehensive stroke recurrence (CSR) model, composed of demographic, clinical and radiological findings, to predict long‐term ischaemic stroke recurrences.

Location of Cerebral Microbleeds May Predict Subsequent Stroke after Transient Ischemic Attack

Dear Sir: The prognostic significance of cerebral microbleeds (CMBs) in ischemic stroke has previously been investigated [1,2]. However, there are as yet no reports regarding the detailed relationship between the CMB location and recurrent stroke following a transient ischemic attack (TIA). We thus aimed to investigate the association between CMB location and subsequent stroke following a TIA in detail. We conducted a hospital-based, multi-center, prospective cohort TIA study (Korean TIA eXpression study, KTX) [2]. Consecutive patients with TIA were enrolled from 11 university hospitals from July 1, 2010 through December 31, 2012. TIA was defined using classic time-based criteria as a focal neurologic deficit lasting less than 24 hours. Patients 40 years or older who were admitted within 24 hours of symptom onset and underwent magnetic resonance imaging, including diffusion-weighted imaging and magnetic resonance angiography, were included in the study. This study was approved by the institutional review boards of all participating hospitals. Written informed consent was obtained from all patients or from their legally authorized representatives. The locations of the CMBs were classified according to the Microbleed Anatomical Rating Scale [3]. We further trichotomized the CMBs as strictly lobar, strictly deep, and mixed based on their locations. Along with CMB location, other neuroimaging variables, including acute ischemic lesions in diffusion-weighted images (single or multiple), prior territorial infarction, lacunar infarction, intracerebral hemorrhage, and white matter hyperintensities were also investigated. Crescendo TIA was defined as at least 3 similar attacks occurring within 7 days from the index TIA.4 Risk stratification scores for ABCD2 and ABCD3-I scores were also determined. Detailed descriptions of the clinical and neuroimaging variables were presented in a previous study [2]. The prognostic significance of CMB location was investigated using the primary endpoint of subsequent stroke within 90 days of index TIA occurrence. Subsequent stroke was assessed at an outpatient clinic or by telephone interview using a structured questionnaire. If necessary, we reviewed medical records to confirm the diagnosis of subsequent stroke. Lesion-positive TIA was not included as an outcome event. We analyzed the data using analysis of variances for continuous variables and the χ2 test and Fisher’s exact test for categorical variables. In multivariable analyses, we estimated hazard ratios for subsequent stroke after TIA and calculated 95% confidential intervals (CIs) with adjustments for possible confounders using Cox proportional hazards models. We reduced the number of covariates using the composite risk score ABCD3-I rather than using individual clinical and neuroimaging variables [2]. Statistical analyses were performed with SPSS statistical software version 21 (IBM SPSS Inc.). A two-sided P<0.05 was considered as the minimum level for statistical significance. Of the 521 consecutive patients with TIA that were screened during the study period, 500 (96.0%) were enrolled. Twenty-one patients were excluded due to protocol violation or consent withdrawal [2]. Recurrent ischemic stroke within 90 days of the TIA occurred in 25 patients. The baseline characteristics of the study subjects are presented in Supplemental Table 1. Strictly lobar CMBs were observed in 16.3%, strictly deep CMBs were found in 53.5%, and mixed CMBs were seen in 30.2% of the patients. The frequently affected sites were the basal ganglia followed by the thalamus and temporo-occipital lobar areas (Supplemental Table 2). Recurrent stroke occurred in 4.2% of patients without CMBs, 14.3% of patients with strictly lobar CMBs, 4.3% of those with strictly deep CMBs, and 38.5% of those with mixed CMBs. The unadjusted hazard ratio of mixed CMB locations for subsequent stroke following TIA was 12.94 (95% CI 4.77-35.13, P value<0.01). According to our multivariable analysis results, mixed CMBs were significantly associated with a risk of recurrent stroke after TIA independently of the number of CMBs (adjusted hazard ratio 19.83, 95% CI 4.21-93.46). We tested several multivariable models and still observed a significant effect of mixed CMB locations on subsequent stroke (Table 1). Table 1. Multivariable Cox proportional hazards models for CMB location and subsequent stroke after TIA Our study reveals that CMBs with mixed locations (lobar and deep) are associated with subsequent stroke following TIA independently of the number of CMBs. The exact mechanism underpinning this association is still unknown. We suggest that the presence of mixed CMB locations may reflect the existence of vulnerable cerebral milieus rather than risk itself. Cortical microinfarcts at autopsy are associated with CMBs in patients with cerebral amyloid angiopathy, which may reflect possible pathophysiological links between CMBs and cerebral ischemia [5]. Chronic hypertension may disrupt cerebral autoregulation of the superficial perforating arteries of pial origin, which results in the exposure of these small arteries to excessive pressure and subsequent damage to smooth muscle cells [6]. Disruption of the internal lamina and thin adventitia of the lobar or corticosubcortical portion of pial arterioles is associated with white matter pathology in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [7]. A recent intriguing study regarding the pathogenesis of CMBs revealed that lobar CMBs were associated with both amyloid-related pathologies and subcortical small vessel disease, whereas deep-seated CMBs were only associated with subcortical small vessel disease [8]. Based on these findings, mixed CMB locations may reflect widespread pathological changes of the cerebral vasculature induced by chronic vascular damage and a hostile milieu associated with subsequent ischemic events. Our study had the limitation of having a small number of main outcome events, which may lead our multivariable models to be over-fitted. Our findings should thus be validated in further large-scale clinical studies. Nevertheless, our study’s strength is that it investigated the association between CMB location and subsequent stroke in a multicenter, prospective cohort with TIA. In conclusion, mixed CMB location was associated with subsequent stroke after TIA occurrence, while strictly lobar or deep CMBs were not. Our data on CMB location imply that the local milieu reflected by the CMBs may predict future ischemic stroke occurrence in patients with TIAs. The exact mechanism underlying these associations should be further investigated.

Kidney dysfunction and silent brain infarction in generally healthy adults

BACKGROUND The association between silent brain infarction (SBI) and estimated glomerular filtration rate (eGFR)-based kidney dysfunction has not yet been definitively confirmed. This study aimed to investigate the association in generally healthy adults without a previous history of stroke or overt kidney disease. METHODS The data from the screening health check-up program in the Seoul National University Hospital Health Promotion Center from January 1, 2009 to December 31, 2013 were used. A total of 2594 subjects who underwent brain MRI as part of health screening were included. SBIs were identified using T2-weighted and FLAIR images. Kidney dysfunction was defined as eGFR<60ml/min/1.73m2. To assess the effect of kidney dysfunction on the small perforating branches of cerebral vessels, subgroup analysis was performed using the presence of SLI as a dependent variable. RESULTS The mean age was 56.8±9.3years, and 1422 subjects (54.8%) were male. The mean eGFR level was 81.9±15.4ml/min/1.73m2. The prevalence rates of kidney dysfunction and SBI were 5.1% and 7.1%, respectively. A higher proportion of subjects with SBI had kidney dysfunction than subjects without SBI (14.6% vs. 4.4%). The number of SBI lesions tended to increase with the progression of kidney dysfunction (p for trend<0.001). In multivariate logistic regression analyses, kidney dysfunction was significantly associated with the presence of SBI (adjusted odd ratio=1.99 to 2.21 in all four models). The same significant association was consistently identified in subgroup analyses using silent lacunar infarction (adjusted odd ratio=1.71 to 1.87 in all four models). CONCLUSION Kidney dysfunction was found to be an independent risk factor for the presence and number of SBI in generally healthy adults. Physicians treating patients with a decreased creatinine-based eGFR level should try to identify and modify the coexisting risk factors of stroke followed by SBI.

Sex-dependent effects of uric acid on cerebral microbleed: a cross-sectional study in the general population.

Elevated serum uric acid (UA) is known to be associated with stroke. However, there is little information on the association between serum UA levels and cerebral microbleed (CMB), a precursor of stroke. Therefore, we investigated the association between UA and CMB in a general population taking into consideration sex‐related differences.