High burden of cerebral white matter lesion in 9 Asian cities.

Age-related white matter lesion (WML) is considered a manifestation of sporadic cerebral small vessel disease and an important pathological substrate for dementia. Asia is notable for its large population with a looming dementia epidemic. Yet, the burden of WML and its associated risk factors across different Asian societies are unknown. Subjects from 9 Asian cities (Bangkok, Bandung, Beijing, Bengaluru, Hong Kong, Kaohsiung, Manila, Seoul, and Singapore) were recruited (n = 5701) and classified into (i) stroke/transient ischemic attack (TIA), (ii) Alzheimer's disease (AD)/mild cognitive impairment (MCI), or (iii) control groups. Data on vascular risk factors and cognitive performance were collected. The severity of WML was visually rated on MRI or CT. The prevalence of moderate-to-severe WML was the highest in subjects with stroke/TIA (43.3%). Bandung Indonesia showed the highest prevalence of WML, adjusted for age, sex, education, disease groups, and imaging modality. Hypertension and hyperlipidemia were significant risk factors for WML, and WML was negatively associated with MMSE in all groups. WML is highly prevalent in Asia and is associated with increasing age, hypertension, hyperlipidemia, and worse cognitive performance. Concerted efforts to prevent WML will alleviate the huge dementia burden in the rapidly aging Asian societies.

Peak width of skeletonized mean diffusivity and its association with age-related cognitive alterations and vascular risk factors.

INTRODUCTION: Only two studies investigated the associations between peak width of skeletonized mean diffusivity (PSMD) and age-related cognitive alterations, whereas none of the studies investigated the association with vascular risk factors. METHODS: We evaluated 801 stroke- and dementia-free elderlies with baseline and 3-year follow-up assessments. Regression analyses were used to assess the association between age-related cognitive functions and PSMD. Simple mediation models were used to study the mediation effect of PSMD between vascular risk factors and age-related cognitive outcomes. RESULTS: PSMD was negatively associated with processing speed at baseline and negatively associated with processing and memory scores at 3-year follow-up. The association between vascular risk factors and age-related cognition was mediated by PSMD, as well as other diffusion tensor imaging markers. DISCUSSION: PSMD is preferred over other diffusion tensor imaging markers as it is sensitive to age-related cognitive alterations and calculation is fully automated. PSMD is proposed as a research tool to monitor age-related cognitive alterations.

Physical activities attenuate the negative cognitive impact from white matter hyperintensities in stroke and TIA patients with low education.

BACKGROUND: The objective of this study is to examine the effects of recent regular participation leisure activities upon cognitive functions between 3 and 6 months after stroke or transient ischemic attack (TIA). We also explored whether the cognitive effects interacted with the severity of white matter hyperintensities (WMH), a marker of cerebral white matter disease, in patients with low or high education. METHODS: Two-hundred and ninety-two subjects with mean age of 66.1 (11.0) years were recruited at median 161(131-180) days post index event. WMH volume was evaluated using a semi-automated method on MRI brain. Cognitive functions were measured using the Montreal Cognitive Assessment (MoCA). Multivariable linear regression analysis was conducted to explore the associations between leisure activity participation with WMH and the moderating effects of leisure activities upon relationship between WMH and MoCA. Analyses were further stratified by low (<6 years) or high education (≥6 years). All models were adjusted with age, sex, and years of education. RESULTS: Physical activity (PA), but not intellectual activity (IA), was negatively related to WMH volume (P < .05). IA exerted a main effect on MoCA performance (b = 3.21, P < .001). PA, but not IA, significantly interacted with WMH volume (b = -0.18, P < .01) on MoCA performance, but the interaction was only significant in the lower education group (b = 0.28, P < .01) but not in the higher education group. CONCLUSIONS: In patients with stroke/TIA, IA confers general cognitive benefits. Regular participation in PA negatively correlated with WMH volume. In patients with low education, PA increases resilience against vascular cognitive impairment.

Risk of intracerebral haemorrhage in Chinese patients with atrial fibrillation on warfarin with cerebral microbleeds: the IPAAC-Warfarin study.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs), which predict future intracerebral haemorrhage (ICH), may guide anticoagulant decisions for atrial fibrillation (AF). We aimed to evaluate the risk of warfarin-associated ICH in Chinese patients with AF with CMBs. METHODS: In this prospective, observational, multicentre study, we recruited Chinese patients with AF who were on or intended to start anticoagulation with warfarin from six hospitals in Hong Kong. CMBs were evaluated with 3T MRI brain at baseline. Primary outcome was clinical ICH at 2-year follow-up. Secondary outcomes were ischaemic stroke, systemic embolism, mortality of all causes and modified Rankin Scale ≥3. Outcome events were compared between patients with and without CMBs. RESULTS: A total of 290 patients were recruited; 53 patients were excluded by predefined criteria. Among the 237 patients included in the final analysis, CMBs were observed in 84 (35.4%) patients, and 11 had ≥5 CMBs. The mean follow-up period was 22.4±10.3 months. Compared with patients without CMBs, patients with CMBs had numerically higher rate of ICH (3.6% vs 0.7%, p=0.129). The rate of ICH was lower than ischaemic stroke for patients with 0 to 4 CMBs, but higher for those with ≥5 CMBs. CMB count (C-index 0.82) was more sensitive than HAS-BLED (C-index 0.55) and CHA2DS2-VASc (C-index 0.63) scores in predicting ICH. CONCLUSIONS: In Chinese patients with AF on warfarin, presence of multiple CMBs may be associated with higher rate of ICH than ischaemic stroke. Larger studies through international collaboration are needed to determine the risk:benefit ratio of oral anticoagulants in patients with AF of different ethnic origins.

Validity and reliability of two alternate versions of the Montreal Cognitive Assessment (Hong Kong version) for screening of Mild Neurocognitive Disorder.

OBJECTIVE: Repeated testing using the Montreal Cognitive Assessment (MoCA) increases risks for practice effects which may bias measurements of cognitive change. The objective of this study is to develop two alternate versions of the MoCA (Hong Kong version; HK-MoCA) and to investigate the validity and reliability of the alternate versions in patients with DSM-5 Mild Neurocognitive Disorder (Mild NCD) and cognitively healthy controls. METHODS: Concurrent validity and inter-scale agreement were examined by Pearson correlation of the total scores between the original and alternate versions and the Bland-Altman Method. Criterion validity of the two alternate versions in differentiating patients with Mild NCD was tested using receiver operating characteristic curve (ROC) analysis. One-month test-retest and inter-rater reliability were examined in 20 participants. Internal consistency of the alternate versions was measured by the Cronbach's α. RESULTS: 30 controls (age 73.4 [4.5] years, 60% female) and 30 patients (age 75.4 [5.5] years, 73% female) with Mild NCD were recruited. Both alternate versions significantly correlated with the original version (r = 0.79-0.87, p<0.001). Mean differences of 0.17 and -0.40 points were found between the total scores of the alternate with the original versions with a consistent level of agreement observed throughout the range of cognitive abilities. Both alternate versions significantly differentiated patients with Mild NCD from healthy controls (area under ROC 0.922 and 0.724, p<0.001) and showed good one-month test-retest reliability (intra-class correlation [ICC] = 0.92 and 0.82) and inter-rater reliability (ICC = 0.99 and 0.87) and high internal consistency (Cronbach α = 0.79 and 0.75). CONCLUSION: The two alternate versions of the HK-MoCA are useful for Mild NCD screening.

Correlation of non-vitamin K antagonist oral anticoagulant exposure and cerebral microbleeds in Chinese patients with atrial fibrillation.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are radiological markers which predict future intracerebral haemorrhage. Researchers are exploring how CMBs can guide anticoagulation decisions in atrial fibrillation (AF). The purpose of this study is to evaluate the correlation of non-vitamin K antagonist oral anticoagulants (NOAC) exposure and prevalence of CMBs in Chinese patients with AF. METHODS: We prospectively recruited Chinese patients with AF on NOAC therapy of ≥30 days for 3T MRI brain for evaluation of CMBs and white matter hyperintensities. Patients with AF without prior exposure to oral anticoagulation were recruited as control group. RESULTS: A total of 282 patients were recruited, including 124 patients in NOAC group and 158 patients in control group. Mean duration of NOAC exposure was 723.8±500.3 days. CMBs were observed in 103 (36.5%) patients. No significant correlation was observed between duration of NOAC exposure and quantity of CMBs. After adjusting for confounding factors (ie, age, hypertension, labile hypertension, stroke history and white matter scores), previous intracerebral haemorrhage was predictive of CMBs (OR 15.28, 95% CI 1.81 to 129.16), particularly lobar CMBs (OR 5.37, 95% CI 1.27 to 22.6). While white matter score was predictive of mixed lobar CMBs (OR 1.65, 95% CI 1.1 to 2.5), both exposure and duration of NOAC use were not predictive of presence of CMBs. CONCLUSIONS: In Chinese patients with AF, duration of NOAC exposure did not correlate with prevalence and burden of CMBs. Further studies with follow-up MRI are needed to determine if long-term NOAC therapy can lead to development of new CMBs.

Converting MMSE to MoCA and MoCA 5-minute protocol in an educationally heterogeneous sample with stroke or transient ischemic attack.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) is psychometrically superior over the Mini-mental State Examination (MMSE) for cognitive screening in stroke or transient ischemic attack (TIA). It is free for clinical and research use. The objective of this study is to convert scores from the MMSE to MoCA and MoCA-5-minute protocol (MoCA-5 min) and to examine the ability of the converted scores in detecting cognitive impairment after stroke or TIA. METHODS: A total of 904 patients were randomly divided into training (n = 623) and validation (n = 281) samples matched for demography and cognition. MMSE scores were converted to MoCA and MoCA-5 min using (1) equipercentile method with log-linear smoothing and (2) Poisson regression adjusting for age and education. Receiver operating characteristics curve analysis was used to examine the ability of the converted scores in differentiating patients with cognitive impairment. RESULTS: The mean education was 5.8 (SD = 4.6; ranged 0-20) years. The entire spectrum of MMSE scores was converted to MoCA and MoCA-5 min using equipercentile method. Relationship between MMSE and MoCA scores was confounded by age and education, and a conversion equation with adjustment for age and education was derived. In the validation sample, the converted scores differentiated cognitively impaired patients with area under receiver operating characteristics curve 0.826 to 0.859. CONCLUSION: We provided 2 methods to convert scores from the MMSE to MoCA and MoCA-5 min based on a large sample of patients with stroke or TIA having a wide range of education and cognitive levels. The converted scores differentiated patients with cognitive impairment after stroke or TIA with high accuracy.

Brain microbleeds, anticoagulation, and hemorrhage risk: Meta-analysis in stroke patients with AF.

OBJECTIVES: To assess the association between cerebral microbleeds (CMBs) and future spontaneous intracerebral hemorrhage (ICH) risk in ischemic stroke patients with nonvalvular atrial fibrillation (AF) taking oral anticoagulants. METHODS: This was a meta-analysis of cohort studies with >50 patients with recent ischemic stroke and documented AF, brain MRI at baseline, long-term oral anticoagulation treatment, and ≥6 months of follow-up. Authors provided summary-level data on stroke outcomes stratified by CMB status. We estimated pooled annualized ICH and ischemic stroke rates from Poisson regression. We calculated odds ratios (ORs) of ICH by CMB presence/absence, ≥5 CMBs, and CMB topography (strictly lobar, mixed, and strictly deep) using random-effects models. RESULTS: We established an international collaboration and pooled data from 8 centers including 1,552 patients. The crude CMB prevalence was 30% and 7% for ≥5 CMBs. Baseline CMB presence (vs no CMB) was associated with ICH during follow-up (OR 2.68, 95% confidence interval [CI] 1.19-6.01, p = 0.017). Presence of ≥5 CMB was related to higher future ICH risk (OR 5.50, 95% CI 2.07-14.66, p = 0.001). The pooled annual ICH incidence increased from 0.30% (95% CI 0.04-0.55) among CMB-negative patients to 0.81% (95% CI 0.17-1.45) in CMB-positive patients (p = 0.01) and 2.48% (95% CI 1.2-6.2) in patients with ≥5 CMBs (p = 0.001). There was no association between CMBs and recurrent ischemic stroke. CONCLUSIONS: The presence of CMB on MRI and the dichotomized cutoff of ≥5 CMBs might identify subgroups of ischemic stroke patients with AF with high ICH risk and after further validation could help in risk stratification, in anticoagulation decisions, and in guiding randomized trials and ongoing large observational studies.

Computerized Cognitive Screen (CoCoSc): A Self-Administered Computerized Test for Screening for Cognitive Impairment in Community Social Centers.

BACKGROUND: Computerized cognitive tests may serve as a preliminary, low-cost method to identify individuals with suspected cognitive impairment in the community. OBJECTIVE: To develop a self-administered computerized test, namely the "Computerized Cognitive Screen (CoCoSc), Hong Kong version", for screening of individuals with cognitive impairment (CI) in community settings. METHODS: The CoCoSc is a 15-min computerized cognitive screen covering memory, executive functions, orientation, attention and working memory, and prospective memory administered on a touchscreen computer. Individuals with CI and cognitively normal controls were administered the CoCoSc and the Montreal Cognitive Assessment (MoCA). Validity of the CoCoSc was assessed based on the relationship with the MoCA using Pearson correlation. Receiver operating characteristic curve (ROC) was used to examine the ability of the CoCoSc to differentiate CI from controls. RESULTS: Fifty-nine individuals with CI and 101 controls were recruited. Seventy-five (46.9%) participants had ≤6 years of education. Performance on the CoCoSc differed between normal and CI groups in both low and high education subgroups. Total scores of the CoCoSc and MoCA were significantly correlated (r = 0.71, p < 0.001). The area under ROC was 0.78, p < 0.001 for the CoCoSc total score in differentiating the CI group from the cognitively normal group. A cut-off of ≤30 on the CoCoSc was associated with a sensitivity of 0.78 and specificity of 0.69. The CoCoSc was well accepted by attendees of community social centers. CONCLUSION: The CoCoSc is a promising computerized cognitive screen for self-administration in community social centers. It is feasible for testing individuals with high or low education levels.

Age-specific trends of atrial fibrillation-related ischaemic stroke and transient ischaemic attack, anticoagulant use and risk factor profile in Chinese population: a 15-year study.

BACKGROUND: Prevalence of atrial fibrillation (AF) is increasing globally, and the fivefold increase in stroke risk constitutes significant healthcare burden. AIMS: We aim to evaluate the trends of AF-related stroke and transient ischaemic attack (AF-stroke/TIA), prior anticoagulant use and their risk factors in different age groups in Chinese population. METHODS: Data were retrieved from the stroke registry at Prince of Wales Hospital. We compared the data at 5-year intervals over a 15-year period (years 1999, 2004, 2009 and 2014). RESULTS: A total of 3894 patients were included, 712 patients had AF-stroke/TIA. Over the 15 years, the total number of ischaemic stroke/TIA fluctuated slightly during the period from year 1999 to 2009, and increased by 21.5% in the year 2014. While AF-stroke/TIA increased continuously with time by 282.1%. Increasing trend of AF-stroke/TIA was observed in all age groups. Absolute growth was highest in patients aged ≥80 years; relative growth was most pronounced in those between 65 and 72 years (>3.5 fold increase). Throughout the 15 years, >70% of AF-stroke/TIA occurred in non-anticoagulated patients, and this proportion increased with age. Increasing trends in both hypertension and ischaemic heart disease were also observed in patients with AF aged ≥73 years. CONCLUSION: AF-stroke/TIA has increased continuously by >2.5 fold in Chinese population over a 15-year period, with the majority of AF-stroke/TIA occurring in non-anticoagulated patients. Strategic planning is needed to optimise anticoagulant use, particularly non-vitamin K antagonist oral anticoagulants in elderly patients, low-income group and those with ischaemic heart disease requiring concomitant antiplatelet therapy.