Eric Ting

Prevalence of cognitive impairment in Chinese: Epidemiology of Dementia in Singapore study

Objective To study the prevalence of and associated factors for cognitive impairment and dementia in community dwelling Chinese from Singapore. Methods This study includes Chinese subjects from the Epidemiology of Dementia in Singapore (EDIS) study, aged ≥60 years, who underwent comprehensive examinations, including cognitive screening with the locally validated Abbreviated Mental Test and Progressive Forgetfulness Questionnaire. Screen positive participants subsequently underwent extensive neuropsychological testing and cerebral MRI. Cognitive impairment no dementia (CIND) and dementia were diagnosed according to internationally accepted criteria. The prevalence of cognitive impairment and dementia were computed per 5 year age categories and gender. To examine the relationship between baseline associated factors and cognitive impairment, we used logistic regression models to compute odd ratios with 95% CI. Results 1538 Chinese subjects, aged ≥60 years, underwent cognitive screening: 171 (15.2%) were diagnosed with any cognitive impairment, of whom 84 were CIND mild, 80 CIND moderate and seven had dementia. The overall age adjusted prevalence of CIND mild was 7.2%; CIND moderate/dementia was 7.9%. The prevalence increased with age, from 5.9% in those aged 60–64 years to 31.3% in those aged 75–79 years and 44.1% in those aged ≥80 years. Multivariate analysis revealed age, diabetes and hyperlipidaemia to be independently associated with cognitive impairment. Conclusions In present study, the overall prevalence of cognitive impairment and dementia in Chinese was 15.2%, which is in the same range as the prevalence reported in Caucasian and other Asian populations.

Early and Continuous Neurologic Improvements after Intravenous Thrombolysis Are Strong Predictors of Favorable Long-term Outcomes in Acute Ischemic Stroke

BACKGROUND Intravenously administered tissue plasminogen activator (IV tPA) remains the only approved therapeutic agent for arterial recanalization in acute ischemic stroke (AIS). Considerable proportion of AIS patients demonstrate changes in their neurologic status within the first 24 hours of intravenous thrombolysis with IV tPA. However, there are little available data on the course of clinical recovery in subacute 2- to 24-hour window and its impact. We evaluated whether neurologic improvement at 2 and 24 hours after IV tPA bolus can predict functional outcomes in AIS patients at 3 months. METHODS Data for consecutive AIS patients treated with IV tPA within 4.5 hours of symptom onset during 2007-2011 were prospectively entered in our thrombolyzed registry. National Institutes of Health Stroke Scale (NIHSS) scores were recorded before IV tPA bolus, at 2 and 24 hours. Early neurologic improvement (ENI) at 2 hours was defined as a reduction in NIHSS score by 10 or more points from baseline or an absolute score of 4 or less points at 2 hours. Continuous neurologic improvement (CNI) was defined as a reduction of NIHSS score by 8 or more points between 2 and 24 hours or an absolute score of 4 or less points at 24 hours. Favorable functional outcomes at 3 months were determined by modified Rankin Scale (mRS) score of 0-1. RESULTS Of 2460 AIS patients admitted during the study period, 263 (10.7%) received IV tPA within the time window; median age was 64 years (range 19-92), with 63.9% being men, a median NIHSS score of 17 points (range 5-35), and a median onset-to-treatment time of 145 minutes (range 57-270). Overall, 130 (49.4%) thrombolyzed patients achieved an mRS score of 0-1 at 3 months. The female gender, age, and baseline NIHSS score were found to be significantly associated with CNI on univariate analysis. On multivariate analysis, NIHSS score at onset and female gender (odds ratio [OR]: 2.218, 95% confidence interval [CI]: 1.140-4.285; P=.024) were found to be independent predictors of CNI. Factors associated with favorable outcomes at 3 months on univariate analysis were younger age, female gender, hypertension, NIHSS score at onset, recanalization on transcranial Doppler (TCD) monitoring or repeat computed tomography (CT) angiography, ENI at 2 hours, and CNI. On multivariate analysis, NIHSS score at onset (OR per 1-point increase: .835, 95% CI: .751-.929, P<.001), 2-hour TCD recanalization (OR: 3.048, 95% CI: 1.537-6.046; P=.001), 24-hour CT angiographic recanalization (OR: 4.329, 95% CI: 2.382-9.974; P=.001), ENI at 2 hours (OR: 2.536, 95% CI: 1.321-5.102; P=.004), and CNI (OR: 7.253, 95% CI: 3.682-15.115; P<.001) were independent predictors of favorable outcomes at 3 months. CONCLUSIONS Women are twice as likely to have CNI from the 2- to 24-hour period after IV tPA. ENI and CNI within the first 24 hours are strong predictors of favorable functional outcomes in thrombolyzed AIS patients.

Multi-stage segmentation of white matter hyperintensity, cortical and lacunar infarcts

Cerebral abnormalities such as white matter hyperintensity (WMH), cortical infarct (CI), and lacunar infarct (LI) are of clinical importance and frequently present in patients with stroke and dementia. Up to date, there are limited algorithms available to automatically delineate these cerebral abnormalities partially due to their complex appearance in MR images. In this paper, we describe an automated multi-stage segmentation approach for labeling the WMH, CI, and LI using multi-modal MR images. We first automatically segment brain tissues (white matter, gray matter, and CSF) based on the T1-weighted image and then identify hyperintense voxels based on the fluid attenuated inversion recovery (FLAIR) image. We finally label the WMH, CI, and LI based on the T1-weighted, T2-weighted, and FLAIR images. The segmentation accuracy is evaluated using a community-based sample of 272 old adults. Our results show that the automated segmentation of the WMH, CI, and LI is comparable with manual labeling in terms of spatial location, volume, and the number of lacunes. Additionally, the WMH volume is highly correlated with the visual grading score based on the Age-Related White Matter Changes (ARWMC) protocol. The evaluations against the manual labeling and ARWMC visual grading suggest that our algorithm provides reasonable segmentation accuracy for the WMH, CI, and LI.

Intracranial Stenosis, Cerebrovascular Diseases, and Cognitive Impairment in Chinese

Extracranial carotid artery disease has been shown to be related to cognitive deficits. However, limited data are available on intracranial stenosis (ICS) and cognitive impairment. We investigate the association between ICS and cognitive impairment in Chinese. Subjects (n=278), recruited from the Epidemiology of Dementia in Singapore Study, underwent comprehensive clinical evaluation, neuropsychological testing, and brain magnetic resonance imaging (MRI), including 3-dimensional-time-of-flight magnetic resonance angiography (MRA). Cognitive function was expressed as composite and domain-specific Z-scores. Cognitive impairment no dementia and dementia were diagnosed according to internationally accepted diagnostic criteria. Linear and logistic regression models were adjusted for age, sex, education, vascular risk factors, and other MRI markers. A total of 29 (10.4%) persons had ICS on MRA, which was significantly associated with both composite cognitive Z-scores [mean difference in Z-score, presence vs. absence of ICS: −0.37 (95% confidence interval: −0.63, −0.12)] and specific domains including executive function, language, visuomotor speed, verbal memory, and visual memory. ICS was also related to significant cognitive impairment (odds ratio: 5.10 [1.24 to 21.02]). With respect to other MRI markers, adjusted for the presence of lacunar infarcts, the associations of ICS with both composite and domain-specific Z-scores, and significant cognitive impairment became nonsignificant; however, adjustment for other MRI markers did not alter these associations. In this Chinese population, presence of ICS was associated with cognitive impairment independent of vascular risk factors. These associations may be mediated through the presence of infarcts.

How temporal evolution of intracranial collaterals in acute stroke affects clinical outcomes.

Objective: We compared intracranial collaterals on pretreatment and day 2 brain CT angiograms (CTA) to assess their evolution and relationship with functional outcomes in acute ischemic stroke (AIS) patients treated with IV tissue plasminogen activator (tPA). Methods: Consecutive AIS patients who underwent pretreatment and day 2 CTA and received IV tPA during 2010–2013 were included. Collaterals were evaluated by 2 independent neuroradiologists using 3 predefined criteria: the Miteff system, the Maas system, and 20-point collateral scale by the Alberta Stroke Program Early CT Score methodology. We stratified our cohort by baseline pre-tPA state of their collaterals and by recanalization status of the primary vessel for analysis. Good outcomes at 3 months were defined by a modified Rankin Scale score of 0–1. Results: This study included 209 patients. Delayed collateral recruitment by any grading system was not associated with good outcomes. All 3 scoring systems showed that collateral recruitment on the follow-up CTA from a baseline poor collateral state was significantly associated with poor outcome and increased bleeding risk. When the primary vessel remained persistently occluded, collateral recruitment was significantly associated with worse outcomes. Interestingly, collateral recruitment was significantly associated with increased mortality in 2 of the 3 grading systems. Conclusions: Not all collateral recruitment is beneficial; delayed collateral recruitment may be different from early recruitment and can result in worse outcomes and higher mortality. Prethrombolysis collateral status and recanalization are determinants of how intracranial collateral evolution affects functional outcomes.

Good Intracranial Collaterals Trump Poor ASPECTS (Alberta Stroke Program Early CT Score) for Intravenous Thrombolysis in Anterior Circulation Acute Ischemic Stroke

Background and Purpose— In acute ischemic stroke, large early infarct size estimated by the Alberta Stroke Program Early CT Score (ASPECTS) is associated with poorer outcomes and is a relative contraindication for recanalization therapies. The state of the intracranial collateral circulation influences the functional outcome and may be a variable to consider before thrombolysis. We evaluated the prognostic effect of the collateral circulation in patients with thrombolyzed acute ischemic stroke who have large early infarct sizes as indicated by low ASPECTS. Materials and Methods— Patients with anterior circulation acute ischemic stroke who received a computed tomographic angiogram and subsequent treatment with intravenous tissue-type plasminogen activator from 2010 to 2013 were studied. Two independent neuroradiologists determined their ASPECTS. We stratified patients using ASPECTS into 2 groups: large volume infarcts (ASPECTS⩽7 points) and small volume infarcts (ASPECTS 8–10). In addition, we evaluated a third group with very large volume infarcts (ASPECTS⩽5 points). We then analyzed the 3 subgroups using the Maas, Tan, and ASPECTS-collaterals grading systems of the computed tomographic angiogram intracranial collaterals. Good outcomes were defined by modified Rankin Scale score of 0 to 2 at 3 months. Results— A total of 300 patients were included in the final analysis. For patients with very large volume infarcts (ASPECTS⩽5 points), univariable analysis showed that younger age, male sex, lower National Institute of Health Stroke Scale (NIHSS), lower systolic blood pressure, and good collaterals by Maas, Tan, or ASPECTS-collaterals grading were predictors of good outcomes. On multivariate analysis, younger age (odds ratio, 0.93; 95% confidence interval, 0.89–0.97; P=0.002) and good collaterals by ASPECTS-collaterals system (odds ratio, 1.34; 95% confidence interval, 1.15–1.57; P<0.001) were associated with good outcomes. Conclusions— In patients with large and very large volume infarcts, good collaterals as measured by the ASPECTS-collaterals system is associated with improved outcomes and can help select patients for intravenous thrombolysis.

Intravenous Thrombolysis for Acute Ischemic Stroke due to Cervical Internal Carotid Artery Occlusion.

BACKGROUND Internal carotid artery (ICA) occlusions are poorly responsive to intravenous thrombolysis with tissue plasminogen activator (IV-tPA) in acute ischemic stroke (AIS). Most study populations have combined intracranial and extracranial ICA occlusions for analysis; few have studied purely cervical ICA occlusions. We evaluated AIS patients with acute cervical ICA occlusion treated with IV-tPA to identify predictors of outcomes. METHODS We studied 550 consecutive patients with AIS who received IV-tPA and identified 100 with pure acute cervical ICA occlusion. We evaluated the associations of vascular risk factors, National Institutes of Health Stroke Scale (NIHSS) score, and leptomeningeal collateral vessel status via 3 different grading systems, with functional recovery at 90 days, mortality, recanalization of the primary occlusion, and symptomatic intracranial hemorrhage (SICH). Modified Rankin Scale score 0-1 was defined as an excellent outcome. RESULTS The 100 patients had mean age of 67.8 (range 32-96) and median NIHSS score of 19 (range 4-33). Excellent outcomes were observed in 27% of the patients, SICH in 8%, and mortality in 21%. Up to 54% of the patients achieved recanalization at 24 hours. On ordinal regression, good collaterals showed a significant shift in favorable outcomes by Maas, Tan, or ASPECTS collateral grading systems. On multivariate analysis, good collaterals also showed reduced mortality (OR .721, 95% CI .588-.888, P = .002) and a trend to less SICH (OR .81, 95% CI .65-1.007, P = .058). Interestingly, faster treatment was also associated with favorable functional recovery (OR 1.028 per minute, 95% CI 1.010-1.047, P = .001). CONCLUSIONS Improved outcomes are seen in patients with early acute cervical ICA occlusion and better collateral circulation. This could be a valuable biomarker for decision making.

External Validation of the Boston Acute Stroke Imaging Scale and M1-BASIS in Thrombolyzed Patients

Background and Purpose— Radiological findings play an essential role in therapeutic decision making and prognostication in acute ischemic stroke (AIS). The Boston Acute Stroke Imaging Scale (BASIS) and Middle Cerebral Artery-BASIS (M1-BASIS) methodologies are rapid purely radiological instruments and easily applicable for patients with AIS. We validated these methods in patients with AIS treated with intravenous tissue-type plasminogen activator. Methods— For BASIS, patients were labeled as having major stroke if there was occlusion of distal internal carotid artery, proximal (both M1 and M2 segments) of middle cerebral artery or the basilar artery, or an Alberta Stroke Program Early CT Score ⩽7. M1-BASIS differs from BASIS by classifying AIS patients with M2 occlusion as a minor stroke. We evaluated these classification systems for predicting functional outcomes (modified Rankin Scale score 0–1) at 3 months. Results— Two hundred sixty-five consecutive AIS patients treated with intravenous tissue-type plasminogen activator were included. On multivariate analysis, younger age (odds ratio, 1.039, 95% confidence interval, 1.009–1.070; P=0.011), lower National Institutes of Health Stroke Scale score (odds ratio, 1.140; 95% confidence interval, 1.073–1.210; P<0.001), and minor stroke by M1-BASIS (odds ratio, 2.376; 95% confidence interval, 1.047–5.393; P=0.039) were independent predictors of good functional outcome. When compared with National Institutes of Health Stroke Scale, the receiver operating characteristic curves for both BASIS (area under the curve, 0.721) and M1-BASIS (area under the curve, 0.795) correlated well with clinical severity scores. M1-BASIS has an additive effect with the National Institutes of Health Stroke Scale score to predict good outcomes. Conclusions— The purely radiological M1-BASIS correlates well with the clinical severity of stroke and can be a reliable prognostication tool in thrombolyzed AIS patients. This system might find an important place in the current era of telestroke.

Mild cognitive impairment subjects with neuroimaging markers of Alzheimer's disease and cerebrovascular disease are more cognitively impaired than mild cognitive impairment subjects with Alzheimer's disease alone

demonstrably strong loadings on d. All observed variables were adjusted for age, gender and education. Conclusions: A latent variable approach to dementia case finding can result in highly accurate dementia endophenotypes. In this case, d has been constructed entirely from verbal measures which could be administered over the telephone in less than 30 minutes. Because a latent construct is “error-free,” we were able to accurately predict the diagnoses of blind clinicians using a verbal battery in a minority sample with demonstrably low educational attainment and variable acculturation. Moreover, the resulting latent construct can be output as a continuous variable, representing dementia’s endophenotype in Hispanics. This can be interrogated for its serum and genetic biomarkers.

Synchronous cardiocerebral infarction in the era of endovascular therapy: which to treat first?

A cardiocerebral ischemic attack (CCI) or a concurrent acute ischemic stroke (AIS) and myocardial infarction (AMI) is a severe event with no clear recommendations for ideal management because of the rarity of the scenario. The narrow time window for treatment and complexity of the treatment decision puts immense pressure on the treating physician. We evaluated this challenging situation at our tertiary center. Using our prospective stroke database out of a total of 555 patients with acute ischemic stroke between 2009 and 2014, we identified five consecutive cases with CCI (incidence 0.009%). Demography, risk factor characteristics, vascular occlusions and treatment approach were recorded. Good functional outcome was defined by the modified Rankin scale (mRS) score of 0–2 points. Out of five patients, AIS was treated with endovascular treatment in three cases, while two were treated with intravenous thrombolysis only. One out of three patients had embolectomy of the brain performed prior to the coronary intervention, while the other two patients underwent coronary intervention first. One patient developed sudden cardiac arrest on day-2 and passed away. CCI is an uncommon and devastating clinical scenario, further research is needed for the ideal management strategy that provides the best outcomes. However, the rarity of the disease does not lend itself to the conduct of a trial easily. We have proposed a considered treatment algorithm based on the current literature and our experience.