Stroke care in Pakistan

Increasing incidence of stroke and lack of infrastructure in both urban and rural areas needs immediate attention in Pakistan. There is a high proportion of young stroke with poor stroke outcomes. Acute stroke care is scarce in Pakistan due to the small number of neurologists (1 neurologist per 1 million population), few stroke units, and limited availability of alteplase (recombinant tissue plasminogen activator) in the country

Urbanization and non-communicable disease mortality in Thailand: an ecological correlation study.

This study provides strong evidence from an LMIC that urbanization is associated with mortality from three lifestyle-associated diseases at an ecological level. Furthermore, our data suggest that both average household income and number of doctors per population are important factors to consider in ecological analyses of mortality

Serum hepatocyte growth factor is associated with small vessel disease in Alzheimer's dementia

Background: While hepatocyte growth factor (HGF) is known to exert cell growth, migration and morphogenic effects in various organs, recent studies suggest that HGF may also play a role in synaptic maintenance and cerebrovascular integrity. Although increased levels of HGF have been reported in brain and cerebrospinal fluid (CSF) samples of patients with Alzheimer's disease (AD), it is unclear whether peripheral HGF may be associated with cerebrovascular disease (CeVD) and dementia. In this study, we examined the association of baseline serum HGF with neuroimaging markers of CeVD in a cohort of pre-dementia (cognitive impaired no dementia, CIND) and AD patients. Methods: Serum samples from aged, Non-cognitively impaired (NCI) controls, CIND and AD subjects were measured for HGF levels. CeVD (cortical infarcts, microinfarcts, lacunes, white matter hyperintensities (WMH) and microbleeds) were assessed by magnetic resonance imaging (MRI). Results: After controlling for covariates, higher levels of HGF were associated with both CIND and AD. Among the different CeVD MRI markers in CIND and AD, only small vessel disease, but not large vessel disease markers were associated with higher HGF levels. Conclusion: Serum HGF may be a useful peripheral biomarker for small vessel disease in subjects with cognitive impairment and AD

Mixed-location cerebral microbleeds as a biomarker of neurodegeneration in a memory clinic population

Cerebral microbleeds (CMBs) in the lobar and deep locations are associated with two distinct pathologies: cerebral amyloid angiopathy and hypertensive arteriopathy. However, the role of mixed-location CMBs in neurodegeneration remains unexplored. We investigated the associations between strictly lobar, strictly deep and mixed-location CMBs with markers of neurodegeneration. This study recruited 477 patients from a memory clinic who underwent 3T MRI scans. CMBs were categorized into strictly lobar, strictly deep and mixed-location. Cortical thickness, white matter volume and subcortical structural volumes were quantified using Free-Surfer. Linear regression models were performed to assess the association between CMBs and cerebral atrophy, and the mean difference (β) and 95% confidence intervals (CIs) were reported. In the regression analyses, mixed-location CMBs were associated with smaller cortical thickness of limbic region [β=-0.01; 95% CI=-0.02,-0.00, p=0.007) as well as with smaller accumbens volume [β=-0.01; 95% CI=-0.02,-0.00, p=0.004) and presubiculum region of hippocampus [β=-0.01; 95% CI=-0.02,-0.00, p=0.002). Strictly lobar CMBs were associated with smaller total white matter volume [β=-0.03; 95% CI=-0.04,-0.01, p<0.001] and with region specific white mat

Serum IL-8 is a marker of white-matter hyperintensities in patients with Alzheimer's disease

Introduction Neuroinflammation and cerebrovascular disease (CeVD) have been implicated in cognitive impairment and Alzheimer's disease (AD). The present study aimed to examine serum inflammatory markers in preclinical stages of dementia and in AD, as well as to investigate their associations with concomitant CeVD. Methods We performed a cross-sectional case–control study including 96 AD, 140 cognitively impaired no dementia (CIND), and 79 noncognitively impaired participants. All subjects underwent neuropsychological and neuroimaging assessments, as well as collection of blood samples for measurements of serum samples interleukin (IL)-6, IL-8, and tumor necrosis factor α levels. Subjects were classified as CIND or dementia based on clinical criteria. Significant CeVD, including white-matter hyperintensities (WMHs), lacunes, and cortical infarcts, was assessed by magnetic resonance imaging. Results After controlling for covariates, higher concentrations of IL-8, but not the other measured cytokines, were associated with both CIND and AD only in the presence of significant CeVD (CIND with CeVD: odds ratios [ORs] 4.53; 95% confidence interval [CI] 1.5–13.4 and AD with CeVD: OR 7.26; 95% CI 1.2–43.3). Subsequent multivariate analyses showed that among the types of CeVD assessed, only WMH was associated with higher IL-8 levels in CIND and AD (WMH: OR 2.81; 95% CI 1.4–5.6). Discussion Serum IL-8 may have clinical utility as a biomarker for WMH in AD. Longitudinal follow-up studies would help validate these findings

Interethnic differences in neuroimaging markers and cognition in Asians, a population-based study

We examined interethnic differences in the prevalence of neuroimaging markers of cerebrovascular and neurodegenerative disease in 3 major Asian ethnicities (Chinese, Malays, and Indians), as well as their role in cognitive impairment. 3T MRI brain scans were acquired from 792 subjects (mean age: 70.0 ± 6.5years, 52.1% women) in the multi-ethnic Epidemiology of Dementia In Singapore study. Markers of cerebrovascular disease and neurodegeneration were identified. Cognitive performance was evaluated using Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and a neuropsychological assessment. Compared to Chinese, Malays had a higher burden of intracranial stenosis (OR: 2.28. 95%CI: 1.23-4.20) and cortical atrophy (β: -0.60. 95%CI: -0.78, -0.41), while Indians had a higher burden of subcortical atrophy (β: -0.23. 95%CI: -0.40, -0.06). Moreover, Malay and Indian ethnicities were likely to be cognitively impaired (OR for Malays: 3.79. 95%CI: 2.29-6.26; OR for Indians: 2.87. 95%CI: 1.74-4.74) and showed worse performance in global cognition (β for Malays: -0.51. 95%CI: -0.66, -0.37; and Indians: -0.32. 95%CI: -0.47, -0.17). A higher burden of cerebrovascular and neurodegenerative markers were found in Malays and Indians when compared to Chinese. Further research is required to fully elucidate the factors and pathways that contribute to these observed differences

Stroke Factors Associated with Thrombolysis Use in Hospitals in Singapore and US: A Cross-Registry Comparative Study

Background and Objectives: This paper aims to describe and compare the characteristics of 2 stroke populations in Singapore and in St. Louis, USA, and to document thrombolysis rates and contrast factors associated with its uptake in both populations. Methods: The stroke populations described were from the Singapore Stroke Registry (SSR) in -Singapore and the Cognitive Rehabilitation Research Group Stroke Registry (CRRGSR) in St. Louis, MO, USA. The registries were compared in terms of demographics and stroke risk factor history. Logistic regression was used to determine factors associated with thrombolysis uptake. Results: A total of 39,323 and 8,106 episodes were recorded in SSR and CRRGSR, respectively, from 2005 to 2012. Compared to CRRGSR, patients in SSR were older, male, and from the ethnic majority. Thrombolysis rates in SSR and CRRGSR were 2.5 and 8.2%, respectively, for the study period. History of ischemic heart disease or atrial fibrillation was associated with increased uptake in both populations, while history of stroke was associated with lower uptake. For SSR, younger age and males were associated with increased uptake, while having a history of smoking or diabetes was associated with decreased uptake. For CRRGSR, ethnic minority status was associated with decreased uptake. Conclusions: The comparison of stroke populations in Singapore and St Louis revealed distinct differences in clinicodemographics of the 2 groups. Thrombolysis uptake was driven by nonethnicity demographics in Singapore. Ethnicity was the only demographic driver of uptake in the CRRGSR population, highlighting the need to target ethnic minorities in increasing access to thrombolysis

Additive effect of cerebral atrophy on cognition in dementia-free elderly with cerebrovascular disease

Objective: To explore the additive effect of neurodegenerative diseases, measured by atrophy, on neurocognitive function in Asian dementia-free elderly with cerebrovascular disease (CeVD). Methods: The present study employed a cross-sectional design and was conducted between 2010 and 2015 among community-dwelling elderly participants recruited into the study. Eligible participants were evaluated with an extensive neuropsychological battery and neuroimaging. The weighted CeVD burden scale comprising markers of both small- and large-vessel diseases was applied, with a score of ≥2, indicating significant CeVD burden. Cortical atrophy (CA) and medial temporal atrophy (MTA) were graded using the global cortical atrophy scale and Schelten's scale, respectively. Global and domain-specific (attention, executive function, language, visuomotor speed, visuoconstruction, visual memory, and verbal memory) neurocognitive performance was measured using a locally validated neuropsychological battery (Vascular Dementia Battery, VDB). Results: A total of 819 dementia-free participants were included in the analysis. Among none-mild CeVD subjects, there was no significant difference in the global cognitive performance across atrophy groups (no atrophy, CA, and CA+MTA). However, in moderate-severe CeVD subjects, CA+MTA showed significantly worse global cognitive performance compared with those with CA alone (mean difference=-0.35, 95% CI -0.60 to -0.11, p=0.002) and those without atrophy (mean difference=-0.46, 95% CI -0.74 to -0.19, p<0.001, p<0.001). In domain-specific cognitive performance, subjects with CA+MTA performed worse than other groups in visual memory (p=0.005), executive function (p=0.001) and visuomotor speed (p<0.001) in moderate-severe CeVD but not in none-mild CeVD. Conclusions and relevance: Atrophy and moderate-severe CeVD burden showed an additive effect on global and domain-specific cognitive performance. This study highlights the importance of investigating the mechanisms of clinico-pathological interactions between neurodegenerative processes and vascular damage, particularly in the pre-dementia stage