Comparison of Factors Associated With Direct Versus Transferred-in Admission to Government-Designated Regional Centers Between Acute Ischemic Stroke and Myocardial Infarction in Korea.

BACKGROUND: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI. METHODS: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed. RESULTS: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI; additionally, age (65-74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI. CONCLUSIONS: Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.

A case report and experience of endovascular treatment for a patient with hemophilia who had a hyperacute ischemic stroke.

No previous study has reported endovascular treatment (EVT) in a patient with hemophilia who had an acute ischemic stroke (AIS). Herein, we report the case of a patient with hemophilia A who presented with hyperacute stroke due to a near occlusion of the proximal internal carotid artery (ICA). A 54-year-old man was admitted to our emergency department with a sudden onset of left-sided weakness that occurred 4 hours prior to admission. He had been diagnosed with congenital hemophilia A during his childhood. Although brain computed tomography revealed no evidence of hemorrhage, we did not consider intravenous thrombolysis because of his bleeding-prone condition. Diffusion-weighted imaging revealed a restricted diffusion in the right anterior and middle cerebral artery territories. Magnetic resonance angiography revealed that the right proximal ICA was nearly occluded and had a residual stump. Digital subtraction angiography revealed a near occlusion of the right proximal ICA with a thread-like lumen. Balloon angioplasty was performed in the proximal ICA, and distal flow was restored, but residual stenosis was observed. Stepwise revascularization by carotid endarterectomy (CEA) was planned instead of immediate carotid stenting. He underwent CEA with preoperative and postoperative coverage of factor VIII and recovered without any bleeding complication.

Sleep Apnea and Early Neurological Deterioration in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Evidence of an association between sleep apnea (SA) and early neurological deterioration (END) in acute phase ischemic stroke is scant. We investigated the prevalence of SA and the impact of SA severity on END in acute ischemic stroke (AIS) patients. METHODS: We prospectively enrolled consecutive AIS patients admitted to our stroke unit within 72 hours of symptom onset. SA severity was assessed with ApneaLink-a validated portable respiratory monitor. SA was defined as an apnea-hypopnea index (AHI) of greater than or equal to 5 per hour. END was defined as an incremental increase in the National Institutes of Health Stroke Scale (NIHSS) score by greater than or equal to 1 point in motor power, or greater than or equal to 2 points in the total score within the first week after admission. RESULTS: Of the 305 patients studied, 254 (83.3%) patients had SA (AHI ≥ 5 per hour), and of these, 114 (37.4%) had mild SA (AHI 5-14 per hour), 59 (19.3%) had moderate SA (AHI 15-29 per hour), and 81 (26.6%) had severe SA (AHI ≥ 30 per hour). Thirty-six (11.8%) patients experienced END: 2 of the 51 (3.9%) patients without SA and 34 of the 254 (14.4%) patients with SA. Multivariable regression analysis showed AHI independently predicted END (odds ratio 1.024; 95% confidence interval 1.006 to 1.042; P = .008). CONCLUSIONS: SA is common in the acute phase of ischemic stroke, and SA severity is associated with the risk of END.

[18F]-THK5351 PET Imaging in Patients With Semantic Variant Primary Progressive Aphasia.

BACKGROUND: Semantic variant primary progressive aphasia (svPPA) has been associated with a variety of proteinopathies, mainly transactive response DNA-binding protein, but also with tau and ß-amyloid. Recently selective tau tracers for positron emission tomography (PET) have been developed to determine the presence of cerebral tau deposits in vivo. Here, we investigated the topographical distribution of THK5351 in svPPA patients. MATERIALS AND METHODS: Five svPPA patients, 14 Alzheimer's disease patients, and 15 age-matched normal controls underwent [F]-THK5351 PET scans, magnetic resonance imaging, and detailed neuropsychological tests. [F]-fluorodeoxyglucose PET was obtained in 3 svPPA patients, whereas the remaining 2 underwent amyloid PET using [F]-flutemetamol. Tau distribution among the 3 groups was compared using regions of interest-based and voxel-based statistical analyses. RESULTS: In svPPA patients, [F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared with the normal controls group (left>right), and in the left inferior and temporal polar region compared with Alzheimer's disease patients. [F]-THK5351 retention inversely correlated with glucose metabolism, whereas regional THK retention correlated with clinical severity. [F]-flutemetamol scans were negative for ß-amyloid. CONCLUSIONS: These findings show that [F]-THK5351 retention may be detected in cortical regions correlating with svPPA pathology.

Yield of Screening Tests for Systemic Vasculitis in Young Adults with Ischemic Stroke.

Systemic vasculitis, which can involve the brain, may be one of the causes of stroke in young adults; therefore, a test panel for systemic vasculitis is considered for some young stroke patients. However, little is known about this test's yield as a screening test in young adults with ischemic stroke. We evaluated the yield of a panel for systemic vasculitis as a screening test in young patients with ischemic stroke. Consecutive patients aged 18-45 years with ischemic stroke between January 2010 and December 2017 were included. They all underwent screening tests for systemic vasculitis including rheumatoid factor, antinuclear antibody, antineutrophil cytoplasmic antibodies, anticardiolipin antibody, lupus anticoagulant, anti-DNA antibody, and anti-Ro/SSA and La/SSB antibodies. Among 3,593 consecutive patients with acute ischemic stroke during the study period, 198 (5.5%) were aged 18-45 years. Only 4 patients (2.0%) were diagnosed with systemic vasculitis; 2 had systemic lupus erythematosus, 1 had Sjogren's syndrome, and 1 had Churg-Strauss syndrome. Vasculitis panel screening in every young ischemic stroke patient is not of high yield unless a vasculitic process is highly suspected based on other systemic symptoms or signs of vasculitis. Screening should be targeted toward persons with clinical suspicion.

Association between body mass index and cortical thickness: among elderly cognitively normal men and women.

BACKGROUND: There is increasing evidence of a relationship between underweight or obesity and dementia risk. Several studies have investigated the relationship between body weight and brain atrophy, a pathological change preceding dementia, but their results are inconsistent. Therefore, we aimed to evaluate the relationship between body mass index (BMI) and cortical atrophy among cognitively normal participants. METHODS: We recruited cognitively normal participants (n = 1,111) who underwent medical checkups and detailed neurologic screening, including magnetic resonance imaging (MRI) in the health screening visits between September 2008 and December 2011. The main outcome was cortical thickness measured using MRI. The number of subjects with five BMI groups in men/women was 9/9, 148/258, 185/128, 149/111, and 64/50 in underweight, normal, overweight, mild obesity, and moderate to severe obesity, respectively. Linear and non-linear relationships between BMI and cortical thickness were examined using multiple linear regression analysis and generalized additive models after adjustment for potential confounders. RESULTS: Among men, underweight participants showed significant cortical thinning in the frontal and temporal regions compared to normal weight participants, while overweight and mildly obese participants had greater cortical thicknesses in the frontal region and the frontal, temporal, and occipital regions, respectively. However, cortical thickness in each brain region was not significantly different in normal weight and moderate to severe obesity groups. Among women, the association between BMI and cortical thickness was not statistically significant. CONCLUSIONS: Our findings suggested that underweight might be an important risk factor for pathological changes in the brain, while overweight or mild obesity may be inversely associated with cortical atrophy in cognitively normal elderly males.

Higher education affects accelerated cortical thinning in Alzheimer's disease: a 5-year preliminary longitudinal study.

BACKGROUND: Epidemiological studies have reported that higher education (HE) is associated with a reduced risk of incident Alzheimer's disease (AD). However, after the clinical onset of AD, patients with HE levels show more rapid cognitive decline than patients with lower education (LE) levels. Although education level and cognition have been linked, there have been few longitudinal studies investigating the relationship between education level and cortical decline in patients with AD. The aim of this study was to compare the topography of cortical atrophy longitudinally between AD patients with HE (HE-AD) and AD patients with LE (LE-AD). METHODS: We prospectively recruited 36 patients with early-stage AD and 14 normal controls. The patients were classified into two groups according to educational level, 23 HE-AD (>9 years) and 13 LE-AD (≤9 years). RESULTS: As AD progressed over the 5-year longitudinal follow-ups, the HE-AD showed a significant group-by-time interaction in the right dorsolateral frontal and precuneus, and the left parahippocampal regions compared to the LE-AD. CONCLUSION: Our study reveals that the preliminary longitudinal effect of HE accelerates cortical atrophy in AD patients over time, which underlines the importance of education level for predicting prognosis.

Amyloid burden, cerebrovascular disease, brain atrophy, and cognition in cognitively impaired patients.

BACKGROUND: We investigated the independent effects of Alzheimer's disease (AD) and cerebrovascular disease (CVD) pathologies on brain structural changes and cognition. METHODS: Amyloid burden (Pittsburgh compound B [PiB] retention ratio), CVD markers (volume of white matter hyperintensities [WMH] and number of lacunae), and structural changes (cortical thickness and hippocampal shape) were measured in 251 cognitively impaired patients. Path analyses were utilized to assess the effects of these markers on cognition. RESULTS: PiB retention ratio was associated with hippocampal atrophy, which was associated with memory impairment. WMH were associated with frontal thinning, which was associated with executive and memory dysfunctions. PiB retention ratio and lacunae were also associated with memory and executive dysfunction without the mediation of hippocampal or frontal atrophy. CONCLUSIONS: Our results suggest that the impacts of AD and CVD pathologies on cognition are mediated by specific brain regions.

Pathogenesis of cerebral microbleeds: In vivo imaging of amyloid and subcortical ischemic small vessel disease in 226 individuals with cognitive impairment.

OBJECTIVE: Cerebral microbleeds (CMBs) are a neuroimaging marker of small vessel disease (SVD) with relevance for understanding disease mechanisms in cerebrovascular disease, cognitive impairment, and normal aging. It is hypothesized that lobar CMBs are due to cerebral amyloid angiopathy (CAA) and deep CMBs are due to subcortical ischemic SVD. We tested this hypothesis using structural magnetic resonance imaging (MRI) markers of subcortical SVD and in vivo imaging of amyloid in patients with cognitive impairment. METHODS: We included 226 patients: 89 with Alzheimer disease-related cognitive impairment (ADCI) and 137 with subcortical vascular cognitive impairment (SVCI). All subjects underwent amyloid imaging with [(11) C] Pittsburgh compound B (PiB) positron emission tomography, and MRI to detect CMBs and markers of subcortical SVD, including the volume of white matter hyperintensities (WMH) and the number of lacunes. RESULTS: Parietal and occipital lobar CMBs counts were higher in PiB(+) ADCI with moderate WMH than PiB(+) ADCI with minimal WMH, whereas PiB(-) patients with SVCI (ie, "pure" SVCI) showed both lobar and deep CMBs. In multivariate analyses of the whole cohort, WMH volume and lacuna counts were positively associated with both lobar and deep CMBs, whereas amyloid burden (PiB) was only associated with lobar CMBs. There was an interaction between lacuna burden and PiB retention on lobar (but not deep) CMBs (p<0.001). INTERPRETATION: Our findings suggest that although deep CMBs are mainly linked to subcortical SVD, both subcortical SVD and amyloid-related pathologies (eg, CAA) contribute to the pathogenesis of lobar CMBs, at least in subjects with mixed lobar and deep CMBs. Furthermore, subcortical SVD and amyloid-related pathologies interact to increase the risk of lobar CMBs.

Blood viscosity in subcortical vascular mild cognitive impairment with versus without cerebral amyloid burden.

BACKGROUND: Subcortical vascular dementia (SVaD) is a common form of dementia, attributed to ischemic small-vessel disease. Blood viscosity (BV) may contribute to the pathophysiology of SVaD. However, SVaD patients with coexisting amyloid deposition may not show differences in BV because their small-vessel disease may result from amyloid angiopathy independently of BV. We, therefore, hypothesized that BV might show different changes compared with control subjects in subcortical vascular mild cognitive impairment (svMCI) that refers to the prodromal stage of SVaD according to cerebral amyloid burden detected by the [(11)C] Pittsburgh compound B (PiB) PET (positron emission tomography), and apolipoprotein 4 (ApoE4) genotype (a known risk factor for vascular and parenchymal amyloid). METHODS: Our subjects consisted of 33 healthy normal controls (NC), 28 patients with PiB(-) svMCI, and 12 with PiB(+) svMCI. They underwent scanning capillary tube viscometer measuring BV during systolic and diastolic phases. RESULTS: Compared with the NC group, the PiB(-) svMCI group showed increased diastolic blood viscosity (DBV) but no difference in systolic blood viscosity (SBV). By contrast, there was no significant difference in SBV and DBV between the NC and PiB(+) svMCI groups. Within the PiB(+) svMCI group, ApoE4(-) subgroup showed increased DBV compared with the ApoE4(+) subgroup. CONCLUSIONS: Increased DBV is an important contributor to the development of "pure" svMCI (ie, without cerebral amyloid deposition). The relationship between BV and PiB(+) svMCI differed according to ApoE genotype, suggesting that the pathogenesis of PiB(+) svMCI might also be heterogeneous.

PCSK9 inhibitor in acute ischemic stroke patient receiving mechanical thrombectomy: early outcomes and safety.

Background: Lipid-lowering therapies are mainstays in reducing recurrence after acute ischemic stroke (AIS). Evolocumab, a Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, is a promising lipid-lowering agent known to decrease LDL cholesterol and mitigate vascular events alongside statins. However, its effects on the early functional outcomes post-mechanical thrombectomy (MT) remain unclear. This study aimed to assess the short-term effects and incidence of bleeding events after the early, off-label use of PCSK9 inhibitors in AIS patients undergoing MT. Methods: We retrospectively analyzed patients who had MT at a Regional Stroke Center from December 2018 to April 2023. Our primary outcome was discharge functional outcomes. Secondary outcomes included early neurologic deterioration (END), symptomatic intracerebral hemorrhage (sICH), 3-month functional outcomes, 3-month recurrence rate, and lipid profiles. Results: Of 261 patients (mean age 69.2 ± 11.7, men 42.9%), 42 were administered evolocumab peri-procedurally. While baseline characteristics were similar between the two groups, evolocumab group demonstrated improved discharge outcomes, with a lower mean NIHSS (8.8 ± 6.8 vs. 12.4 ± 9.8, p = 0.02) and a higher percentage of patients with discharge mRS ≤ 3 (52.4% vs. 35.6%, p = 0.041). The 3-month follow-up show a non-significant trend toward an improved outcome in the evolocumab group. Multivariable analysis indicated that evolocumab had a potential impact on favorable discharge outcomes (aOR 1.98[0.94-4.22] for mRS ≤ 3 and 0.47[0.27-0.84] for lower ordinal mRS). Notably, evolocuamb users exhibited fewer instances of END and sICH, although they do not reach statistical significance. Additionally, the evolocumab group demonstrated potential benefits in LDL cholesterol reduction over time. Conclusion: Early use of evolocumab in AIS patients undergoing MT appeared to be safe and associated with better early functional outcomes. The potential benefit of the PCSK9 inhibitor shown here warrants further prospective studies.

Alterations of Structural Network Efficiency in Early-Onset and Late-Onset Alzheimer's Disease.

BACKGROUND AND PURPOSE: Early- and late-onset Alzheimer's disease (EOAD and LOAD, respectively) share the same neuropathological hallmarks of amyloid and neurofibrillary tangles but have distinct cognitive features. We compared structural brain connectivity between the EOAD and LOAD groups using structural network efficiency and evaluated the association of structural network efficiency with the cognitive profile and pathological markers of Alzheimer's disease (AD). METHODS: The structural brain connectivity networks of 80 AD patients (47 with EOAD and 33 with LOAD) and 57 healthy controls were reconstructed using diffusion-tensor imaging. Graph-theoretic indices were calculated and intergroup differences were evaluated. Correlations between network parameters and neuropsychological test results were analyzed. The correlations of the amyloid and tau burdens with network parameters were evaluated for the patients and controls. RESULTS: Compared with the age-matched control group, the EOAD patients had increased global path length and decreased global efficiency, averaged local efficiency, and averaged clustering coefficient. In contrast, no significant differences were found in the LOAD patients. Locally, the EOAD patients showed decreases in local efficiency and the clustering coefficient over a wide area compared with the control group, whereas LOAD patients showed such decreases only within a limited area. Changes in network parameters were significantly correlated with multiple cognitive domains in EOAD patients, but only with Clinical Dementia Rating Sum-of-Boxes scores in LOAD patients. Finally, the tau burden was correlated with changes in network parameters in AD signature areas in both patient groups, while there was no correlation with the amyloid burden. CONCLUSIONS: The impairment of structural network efficiency and its effects on cognition may differ between EOAD and LOAD.

Cerebellar atrophy in patients with subcortical-type vascular cognitive impairment.

Recent studies suggest that the role of the cerebellum extends into cognitive regulation and that subcortical vascular dementia (SVaD) can result in cerebellar atrophy. However, there has been no evaluation of the cerebellar volume in the preclinical stage of SVaD. We aimed to compare cerebellar volume among patients with amnestic mild cognitive impairment (aMCI) and subcortical vascular mild cognitive impairment (svMCI) and evaluate which factors could have contributed to the cerebellar volume. Participants were composed of 355 patients with aMCI, svMCI, Alzheimer's disease (AD), and SVaD. Cerebellar volumes were measured using automated methods. A direct comparison of the cerebellar volume in SVaD and AD groups showed that the SVaD group had a statistically smaller cerebellar volume than the AD group. Additionally, the svMCI group had a smaller cerebellar volume than the aMCI group, with the number of lacunes (especially in the supratentorial regions) being associated with cerebellar volume. Cerebellar volumes were associated with some neuropsychological tests, digit span backward and ideomotor apraxia. These findings suggest that cerebellar atrophy may be useful in differentiating subtypes of dementia and the cerebellum plays a potential role in cognition.

Stroke in Women: A Review Focused on Epidemiology, Risk Factors, and Outcomes.

Stroke is a particularly important issue for women. Women account for over half of all persons who experienced a stroke. The lifetime risk of stroke is higher in women than in men. In addition, women have worse stroke outcomes than men. Several risk factors have a higher association with stroke in women than in men, and women-specific risk factors that men do not have should be considered. This focused review highlights recent findings in stroke epidemiology, risk factors, and outcomes in women.

Angiotensin-converting enzyme insertion/deletion gene polymorphism and the progression of cerebral microbleeds.

Background and purpose: The angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism has been studied as a genetic candidate for cerebral small vessel disease (CSVD). However, no previous study has evaluated the relationship between the ACE I/D polymorphism and cerebral microbleed (CMB), an important CSVD marker. We evaluated the association between ACE I/D polymorphisms and 2-year changes in CMBs. Methods: The CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Of 256 subjects, 186 participants who underwent a 2-year follow-up brain scan and ACE genotyping were included. Our analysis was conducted by dividing the ACE genotype into two groups (DD vs. ID/II) under the assumption of the recessive effects of the D allele. A linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between the DD and combined ID/II genotypes. Results: Among 186 patients included in this study, 24 (12.9%) had the DD genotype, 91 (48.9%) had the ID genotype, and 71 (38.2%) had the II genotype. Baseline clinical characteristics and cerebral small vessel disease markers were not different between the two groups (DD vs. ID/II) except for the prevalence of hypertension (DD 66.7% vs. ID/II 84.6%; p = 0.04). A multivariate linear mixed-effects model showed that the DD carriers had a greater increase in total CMB counts than the ID/II carriers after adjusting for the baseline number of CMBs, age, sex, and hypertension (estimated mean of difference [standard error (SE)] = 1.33 [0.61]; p = 0.03). When we performed an analysis of cases divided into deep and lobar CMBs, only lobar CMBs were significantly different between the two groups (estimated mean of difference [SE] = 0.94 [0.42]; p = 0.02). Conclusion: The progression of CMBs over 2 years was greater in the ACE DD carriers compared with the combined II/ID carriers. The results of our study indicate a possible association between the ACE I/D polymorphism and CMB. A study with a larger sample size is needed to confirm this association.

Multiphasic perfusion computed tomography as a predictor of collateral flow in acute ischemic stroke: comparison with digital subtraction angiography.

BACKGROUND: Assessing collateral status is important in acute ischemic stroke. The purpose of this study was to compare multiphasic perfusion computed tomography (MPCT) with digital subtraction angiography (DSA) in predicting leptomeningeal collateral flow in acute middle cerebral artery (MCA) infarction. METHODS: Consecutive patients underwent MPCT and DSA for acute MCA infarction that presented within 6 h of symptom onset. We included patients who showed MCA occlusion in the same location on both modalities and assessed the agreement rate and correlation between the MPCT and DSA collateral grades. RESULTS: Of 54 patients, 44 (81.5%) had proximal MCA (M1) occlusions and 10 (18.5%) had distal MCA (M2) occlusions based on MPCT and DSA. The κ-coefficients were 0.87 and 0.81 in the MPCT and DSA collateral grade systems, respectively. Forty-four patients (81.5%) belonged to the same category in both collateral-grading systems. MPCT collateral grades correlated positively with those of DSA (Spearman's correlation coefficient 0.827, p < 0.001). CONCLUSION: Our data show that MPCT can predict leptomeningeal collateral flow in acute ischemic stroke. Based on collateral status assessed by MPCT, different therapeutic approaches might be warranted.

Sex differences in the progression of cerebral microbleeds in patients with concomitant cerebral small vessel disease.

Background and purpose: Sex differences in cerebral microbleeds (CMBs) are not well-known. We aimed to assess the impact of sex on the progression of CMBs. Methods: The CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Out of 256 subjects, 189 participants with a follow-up brain scan were included in the analysis. The linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between men and women. Results: A total of 65 men and 124 women were analyzed. There were no significant differences in the prevalence (70.8 vs. 71.8%; P = 1.000) and the median [interquartile range (IQR)] number of total CMBs [1 (0-7) vs. 2 (0-7); P = 0.810] at baseline between men and women. The median (IQR) increase over 2 years in the number of CMBs was statistically higher in women than in men [1 (0-2) vs. 0 (0-1), P = 0.026]. The multivariate linear mixed-effects model showed that women had a significantly greater increase in the number of total, deep, and lobar CMBs compared to men after adjusting for age and the baseline number of CMBs [estimated log-transformed mean of difference between women and men: 0.040 (P = 0.028) for total CMBs, 0.037 (P = 0.047) for deep CMBs, and 0.047 (P = 0.009) for lobar CMBs]. Conclusion: The progression of CMB over 2 years was significantly greater in women than in men.

Comparisons of Prehospital Delay and Related Factors Between Acute Ischemic Stroke and Acute Myocardial Infarction.

Background Prehospital delay is an important contributor to poor outcomes in both acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We aimed to compare the prehospital delay and related factors between AIS and AMI. Methods and Results We identified patients with AIS and AMI who were admitted to the 11 Korean Regional Cardiocerebrovascular Centers via the emergency room between July 2016 and December 2018. Delayed arrival was defined as a prehospital delay of >3 hours, and the generalized linear mixed-effects model was applied to explore the effects of potential predictors on delayed arrival. This study included 17 895 and 8322 patients with AIS and AMI, respectively. The median value of prehospital delay was 6.05 hours in AIS and 3.00 hours in AMI. The use of emergency medical services was the key determinant of delayed arrival in both groups. Previous history, 1-person household, weekday presentation, and interhospital transfer had higher odds of delayed arrival in both groups. Age and sex had no or minimal effects on delayed arrival in AIS; however, age and female sex were associated with higher odds of delayed arrival in AMI. More severe symptoms had lower odds of delayed arrival in AIS, whereas no significant effect was observed in AMI. Off-hour presentation had higher and prehospital awareness had lower odds of delayed arrival; however, the magnitude of their effects differed quantitatively between AIS and AMI. Conclusions The effects of some nonmodifiable and modifiable factors on prehospital delay differed between AIS and AMI. A differentiated strategy might be required to reduce prehospital delay.

Effects of Alzheimer's and Vascular Pathologies on Structural Connectivity in Early- and Late-Onset Alzheimer's Disease.

Early- and late-onset Alzheimer's disease (AD) patients often exhibit distinct features. We sought to compare overall white matter connectivity and evaluate the pathological factors (amyloid, tau, and vascular pathologies) that affect the disruption of connectivity in these two groups. A total of 50 early- and 38 late-onset AD patients, as well as age-matched cognitively normal participants, were enrolled and underwent diffusion-weighted magnetic resonance imaging to construct fractional anisotropy-weighted white matter connectivity maps. [18F]-THK5351 PET, [18F]-Flutemetamol PET, and magnetic resonance imaging were used for the evaluation of tau and related astrogliosis, amyloid, and small vessel disease markers (lacunes and white matter hyperintensities). Cluster-based statistics was performed for connectivity comparisons and correlation analysis between connectivity disruption and the pathological markers. Both patient groups exhibited significantly disrupted connectivity compared to their control counterparts with distinct patterns. Only THK retention was related to connectivity disruption in early-onset AD patients, and this disruption showed correlations with most cognitive scores, while late-onset AD patients had disrupted connectivity correlated with amyloid deposition, white matter hyperintensities, and lacunes in which only a few cognitive scores showed associations. These findings suggest that the pathogenesis of connectivity disruption and its effects on cognition are distinct between EOAD and LOAD.

Comparison of Longitudinal Changes of Cerebral Small Vessel Disease Markers and Cognitive Function Between Subcortical Vascular Mild Cognitive Impairment With and Without NOTCH3 Variant: A 5-Year Follow-Up Study.

No study yet has compared the longitudinal course and prognosis between subcortical vascular cognitive impairment patients with and without genetic component. In this study, we compared the longitudinal changes in cerebral small vessel disease markers and cognitive function between subcortical vascular mild cognitive impairment (svMCI) patients with and without NOTCH3 variant [NOTCH3(+) svMCI vs. NOTCH3(-) svMCI]. We prospectively recruited patients with svMCI and screened for NOTCH3 variants by sequence analysis for mutational hotspots in the NOTCH3 gene. Patients were annually followed-up for 5 years through clinical interviews, neuropsychological tests, and brain magnetic resonance imaging. Among 63 svMCI patients, 9 (14.3%) had either known mutations or possible pathogenic variants. The linear mixed effect models showed that the NOTCH3(+) svMCI group had much greater increases in the lacune and cerebral microbleed counts than the NOTCH3(-) svMCI group. However, there were no significant differences between the two groups regarding dementia conversion rate and neuropsychological score changes over 5 years.