Cross-sectional association of continuous glucose monitoring-derived metrics with cerebral small vessel disease in older adults with type 2 diabetes.

AIM: To examine cross-sectional associations between continuous glucose monitoring (CGM)-derived metrics and cerebral small vessel disease (SVD) in older adults with type 2 diabetes. MATERIALS AND METHODS: In total, 80 patients with type 2 diabetes aged ≥70 years were analysed. Participants underwent CGM for 14 days. From the CGM data, we derived mean sensor glucose, percentage glucose coefficient of variation, mean amplitude of glucose excursion, time in range (TIR, 70-180 mg/dl), time above range (TAR) and time below range metrics, glycaemia risk index and high/low blood glucose index. The presence of cerebral SVD, including lacunes, microbleeds, enlarged perivascular spaces and white matter hyperintensities, was assessed, and the total number of these findings comprised the total cerebral SVD score (0-4). Ordinal logistic regression analyses were performed to examine the association of CGM-derived metrics with the total SVD score. RESULTS: The median SVD score was 1 (interquartile range 0-2). Higher hyperglycaemic metrics, including mean sensor glucose, TAR >180 mg/dl, TAR >250 mg/dl, and high blood glucose index and glycaemia risk index, were associated with a higher total SVD score. In contrast, a higher TIR (per 10% increase) was associated with a lower total SVD score (odds ratio 0.73, 95% confidence interval 0.56-0.95). Glycated haemoglobin, percentage glucose coefficient of variation, mean amplitude of glucose excursions, time below range and low blood glucose index were not associated with total cerebral SVD scores. CONCLUSIONS: The hyperglycaemia metrics and TIR, derived from CGM, were associated with cerebral SVD in older adults with type 2 diabetes.

Early-onset Alzheimer Disease Associated With Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease of the central nervous system. Although recent reports have noted that cognitive impairment is common in NMOSD, little longitudinal information is available on the trajectories of cognitive function in the disease. Here, we report a case of a 55-year-old woman with an 11-year history of NMOSD who visited our memory clinic for progressive memory loss. She was diagnosed with early-onset Alzheimer disease based on amyloid and tau positron emission tomography imaging biomarkers. This is the first report of early-onset Alzheimer disease in a patient with NMOSD. Complications of Alzheimer disease should be considered when patients with NMOSD exhibit rapid cognitive decline. More longitudinal studies of NMOSD with cognitive impairment are needed.

Quantitative Analysis of White Matter Hyperintensity: Comparison of Magnetic Resonance Imaging Image Analysis Software.

OBJECTIVE: White matter hyperintensity (WMH), defined as abnormal signals on magnetic resonance imaging (MRI), is an important clinical indicator of aging and dementia. Although MRI image analysis software can automatically detect WMH, the quantitative accuracy of periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) is unknown. MATERIALS AND METHODS: This study was a sub-analysis of MRI data from an ongoing hospital-based prospective cohort study (the Gimlet study). Between March 2016 and March 2017, we enrolled patients who visited our memory clinic and agreed to undergo medical assessments of cognitive function and fecal examination to study the gut microbiome. Participants with a history of stroke were excluded. WMH was independently quantitatively analyzed using two MRI imaging analysis software modalities: SNIPER and FUSION. Intraclass correlation coefficients and the mean difference in volume were calculated and compared between modalities. RESULTS: The data of 87 patients (49 women, mean age 74.8 ± 7.9 years) were analyzed. Both total WMH and DWMH volumes obtained using FUSION were greater (p < 0.001), and PVH volume was smaller (p < 0.001) than those obtained using SNIPER. Intraclass correlation coefficients for the lesion measurements of WMH, PVH, and DWMH between the different software were 0.726 (p < 0.001), 0.673 (p < 0.001), and 0.048 (p = 0.231), respectively. CONCLUSIONS: There were significant differences in the quantitative data of WMH between the two MRI imaging analysis software modalities. Thus, care should be taken for quantitative assessments of WMH.

The Association between Cerebral Small Vessel Disease and the Gut Microbiome: A Cross-Sectional Analysis.

BACKGROUND: Recent studies have demonstrated an association between the gut microbiome and cognitive function. However, the associations between the gut microbiome and brain parenchyma damage, and their underlying mechanisms, remain unclear. MATERIALS AND METHODS: We performed a cross-sectional sub-analysis using data from our prospective cohort study to determine the association between the gut microbiome and cerebral small vessel disease (SVD). We assessed patient demographics, risk factors, cognitive function, brain imaging, voxel-based specific regional analysis system for Alzheimer's Disease (VSRAD, indicating brain atrophy), and the gut microbiome as indicated by enterotypes and faecal microbiome metabolites. We then analysed the associations between total SVD scores, cognitive function, and the gut microbiome. RESULTS: We analysed data from 87 patients without dementia or a history of stroke, 64 of whom exhibited mild cognitive impairment. Higher total SVD scores were associated with cognitive decline and behavioural and psychological symptoms. Compared with all other patients, patients with enterotype I (Bacteroides >30%) were more likely to have cognitive decline (median scores: Mini-Mental State Examination, 25 vs. 27, P = 0.047; Clinical Dementia Rating-Sum of Boxes, 1.5 vs. 0.5, P = 0.002) and present with cerebral SVD and high VSRAD scores (1.01 vs. 0.57, P = 0.012). Furthermore, faecal metabolites were significantly higher in patients with higher total SVD scores compared with those with lower scores. Multivariable logistic regression analyses indicated that certain gut microbiomes may double the risk of white matter hyperintensity. CONCLUSIONS: The gut microbiome is associated with cerebral SVD.

Cilostazol May Decrease Plasma Inflammatory Biomarkers in Patients with Recent Small Subcortical Infarcts: A Pilot Study.

BACKGROUND: The mechanism of progressive neurological deficit in patients with recent small subcortical infarcts has not yet been clarified. Inflammatory biomarkers and the use of cilostazol may be associated with this phenomenon. METHODS: Between May 2013 and April 2014, we evaluated consecutive first-ever patients with stroke due to recent small subcortical infarcts within 48 hours of onset. We divided patients into 2 groups according to the use of antiplatelet agents (cilostazol with or without aspirin versus aspirin alone). Plasma biomarkers such as matrix metalloproteinase-9, interleukin-6, high sensitive C-reactive protein, and amyloid ß precursor protein (APP770, indicating endothelial dysfunction) were measured twice: (1) within 24 hours; and (2) 1 week after their admission. Multivariable logistic regression analyses were performed to identify the variables independently associated with progressive neurological deficit and poor functional outcome. RESULTS: We analyzed 41 patients (male: 63.4%, mean age: 70.8 years). Most of the patients (90%) who were treated with cilostazol were concomitantly treated with aspirin. Matrix metalloproteinase-9 and high sensitive C-reactive protein were higher in patients with progressive neurological deficit compared with those without. APP770 were more likely to be decreased in cilostazol group compared with aspirin group. Multivariable analyses show that traditional risk factors such as age and National Institutes of Health Stroke Scale scores were independently associated with both progressive neurological deficit and poor functional outcome. CONCLUSIONS: Inflammatory biomarkers may be associated with progressive neurological deficit. Early initiation of cilostazol may decrease the levels of plasma biomarkers.

A homozygous mutation of VWA3B causes cerebellar ataxia with intellectual disability.

BACKGROUND: Hereditary cerebellar ataxia constitutes a heterogeneous group of neurodegenerative disorders, occasionally accompanied by other neurological features. Genetic defects remain to be elucidated in approximately 40% of hereditary cerebellar ataxia cases in Japan. We attempted to identify the gene responsible for autosomal recessive cerebellar ataxia with intellectual disability. METHODS: The present study involved three patients in a consanguineous Japanese family. Neurological examination and gene analyses were performed in all family members. We performed genome-wide linkage analysis including single nucleotide polymorphism arrays, copy-number variation analysis and whole exome sequencing. To clarify the functional alteration resulting from the identified mutation, we performed cell viability assay of cultured cells expressing mutant protein. RESULTS: One homozygous region shared among the three patients on chromosomes 2p16.1-2q12.3 was identified. Using whole exome sequencing, six homozygous variants in genes in the region were detected. Only one variant, VWA3B c.A1865C, results in a change of a highly conserved amino acid (p.K622T) and was not present in control samples. VWA3B encodes a von Willebrand Factor A Domain-Containing Protein 3B with ubiquitous expression, including the cerebellum. The viability of cultured cells expressing the specific K622T mutation was proved to decrease through the activation of apoptotic pathway. CONCLUSIONS: Mutated VWA3B was found to be likely associated with cerebellar degeneration with intellectual disability. Although a rare cause of cerebellar degeneration, these findings indicate a critical role for VWA3B in the apoptosis pathway in neuronal tissues.

Decrease of Hyperintense Vessels on Fluid-Attenuated Inversion Recovery Predicts Good Outcome in t-PA Patients.

BACKGROUND AND PURPOSE: Hyperintense vessels (HV) detected on fluid-attenuated inversion recovery (FLAIR) in patients with acute ischemic stroke (AIS) indicate cerebral hypoperfusion. However, the clinical meaning of changes in HV is yet to be clarified. Here, we investigated serial changes to HV in patients with AIS who received tissue plasminogen activator (t-PA) therapy. METHODS: We studied t-PA patients presenting with HV on FLAIR in the middle cerebral artery territory. Patients underwent brain MRI 1 h before and after t-PA infusion. HV scores (range 1-7) were evaluated according to Alberta Stroke Program Early Computed Tomography Score territories, and then by subtracting HV scores at 1 h after t-PA infusion from those on admission, with a result of >1 defined as decrease in HV score (DHV). Patients were divided into 2 groups based on the presence or absence of DHV. Multivariate logistic regression analysis was conducted to identify variables independently associated with good outcome (modified Rankin Scale score at 90 days after stroke onset of 0-1). RESULTS: A total of 118 consecutive patients were enrolled (73 men; mean age 76 ± 9.7; median initial National Institutes of Health Stroke Scale (NIHSS) 13; median initial HV score 5), of whom 52 (44%) had DHV. Patients with DHV showed a significantly lower NIHSS time course (p < 0.001) and significantly smaller infarct volume time course (p < 0.001) compared to those without DHV. Multivariate analysis showed that DHV was independently associated with good outcome (OR 3.89; 95% CI 1.55-9.77; p < 0.01). The sensitivity and specificity of DHV for good outcome were 70 and 68%, respectively. CONCLUSION: A DHV on FLAIR predicts good outcome in patients receiving t-PA.

Safety and efficacy of non-vitamin K oral anticoagulant treatment compared with warfarin in patients with non-valvular atrial fibrillation who develop acute ischemic stroke or transient ischemic attack: a multicenter prospective cohort study (daVinci study).

The safety and efficacy of non-vitamin K oral anticoagulant (NOAC) compared with warfarin in treating patients with non-valvular atrial fibrillation (NVAF) who developed acute ischemic stroke or transient ischemic attack (AIS/TIA), particularly those receiving tissue-plasminogen activator (tPA) therapy, remains unclear. Between April 2012 and December 2014, we conducted a multicenter prospective cohort study to assess the current clinical practice for treating such patients. We divided the patients into two groups according to the administration of oral anticoagulants (warfarin or NOACs) and tPA therapy. The risk of any hemorrhagic or ischemic event was compared within 1 month after the onset of stroke. We analyzed 235 patients with AIS/TIA including 73 who received tPA therapy. Oral anticoagulants were initiated within 2-4 inpatient days. NOACs were administered to 49.8 % of patients, who were predominantly male, younger, had small infarcts, lower NIHSS scores, and had a lower all-cause mortality rate (0 vs. 4.2 %, P = 0.06) and a lower risk of any ischemic events (6.0 vs. 7.6 %, P = 0.797) compared with warfarin users. The prevalence of all hemorrhagic events was equivalent between the two groups. Early initiation of NOACs after tPA therapy appeared to lower the risk of hemorrhagic events, although there was no significant difference (0 vs. 5.6 %, P = 0.240). Although more clinicians are apt to prescribe NOACs in minor ischemic stroke, NOAC treatment may provide a potential benefit in such cases. Early initiation of NOACs after tPA therapy may reduce the risk of hemorrhagic events compared with warfarin.

Post Stroke Dysglycemia and Acute Infarct Volume Growth: A Study Using Continuous Glucose Monitoring.

BACKGROUND: The aim of the present study was to clarify the effect of glucose profiles after stroke, which was assessed by a continuous glucose monitoring (CGM) device. METHODS: Acute ischemic stroke patients within 24 h of onset were prospectively studied. CGM was performed for 72 h after admission. CGM parameters were evaluated as follows: (1) mean glucose level, (2) area under the curve (AUC) for glucose level >140 mg/dl and (3) SD of the glucose level. Infarct volume was measured at admission and 24 and 72 h after admission using diffusion-weighted imaging. CGM data and infarct volume growth were compared at 24 and 72 h. RESULTS: Seventy-eight patients were enrolled in the present study. Spearman's rank correlation coefficients showed that both the mean glucose level (r = 0.433, p < 0.001 for 24 h; r = 0.308, p = 0.006 for 72 h) and AUC >140 mg/dl (r = 0.417, p < 0.001 for 24 h; r = 0.277, p = 0.014 for 72 h) were significantly correlated with acute infarct volume growth. The SD of the glucose level was associated with infarct volume growth at 24 h (r = 0.303, p = 0.007), but not 72 h (r = 0.195, p = 0.088). CONCLUSION: Post-stroke hyperglycemia was associated with infarct volume growth during the acute phase of ischemic stroke.

[Frailty and sarcopenia: a new bridge to dementia].

Frailty is a predictor of functional decline, falls, hospitalization, and mortality. Fried et al. developed the frailty index, which include 5 simple items: weight loss, weakness, exhaustion, slowness, and low activity. Likewise, sarcopenia indicates an age-related decline in skeletal muscle mass as well as muscle function, which may result in reduced physical capability, poorer quality of life, impaired cardiopulmonary performance, unfavorable metabolic effects, falls, disability, and mortality. Both frailty and sarcopenia could be associated with mild cognitive impairment which leads to dementia. Thus, early initiation of a comprehensive geriatric health examination and a multidomain intervention such as diet, exercise, cognitive training, and vascular risk monitoring may be useful to prevent frailty and sarcopenia in community-dwelling older adults.

Intracranial Hemorrhage Caused by Non-Vitamin K Antagonist Oral Anticoagulants (NOACs)- Multicenter Retrospective Cohort Study in Japan.

BACKGROUND: We conducted a multicenter retrospective cohort study to elucidate the characteristics of intracranial hemorrhage (ICH) in patients with atrial fibrillation treated with non-vitamin K antagonist oral anticoagulants (NOACs). METHOD AND RESULTS: We sent a questionnaire to the directors of 241 stroke centers in Japan to establish the clinical characteristics of NOAC-associated cerebral hemorrhage (CH), including hematoma size, hematoma enlargement (HE) and in-hospital mortality of patients treated in their institutions. We undertook a literature review to establish the clinical characteristics of warfarin-associated CH and compared these with our data. We received 174 responses (72.2%), of which 67 (38.5%) gave anonymous details of 130 eligible patients (male, 67.7%; mean age, 77.3±8.3 years, in-hospital mortality rate, 11.5%). We judged that 87 of the 130 patients had presented with CH: one-fifth had taken antiplatelet drugs. We found that the incidences of HE and mortality in the 87 patients presenting with NOAC-associated CH were lower than would have been expected in those with warfarin-associated CH (17% vs. 26%, and 16% vs. 35%, respectively). CONCLUSIONS: More than half the stroke center directors who responded to our questionnaire had not experienced cases of NOAC-associated ICH. Compared with warfarin, NOACs appear to present a lower risk of HE and death in patients with atrial fibrillation who develop CH.

Deep Cerebral Microbleeds and Renal Dysfunction in Patients with Acute Lacunar Infarcts.

BACKGROUND: Cerebral small-vessel disease (SVD) is associated with renal dysfunction such as chronic kidney disease. Although cerebral microbleeds (CMBs) are common in patients with acute lacunar infarcts (ALI), the association between renal dysfunction and CMBs in such patients remains unclear. METHODS: Between April 2007 and March 2013, we evaluated consecutive first-ever ALI patients, who were admitted to our hospital within 24 hours of stroke onset. CMBs were defined as focal areas of signal loss in brain parenchyma less than 5 mm on T2(∗)-weighted gradient-echo imaging. Renal dysfunction was defined as an estimated glomerular filtration rate less than 60 mL/minute/1.73 m(2) on admission. Correlations between renal dysfunction and the presence (model 1) and location of CMBs (model 2; any deep or infratentorial CMBs) were determined by multivariable logistic regression analyses. RESULTS: Among 152 patients (33.6% men; mean age, 67.6 years), 53 had CMBs. Patients with CMBs were older (69.9 versus 66.3 years, P = .03) and had a higher frequency of white matter hyperintensity (WMH; 62.3% versus 25.3%, P < .001), silent lacunar infarcts (SLI; 75.5% versus 43.3%, P < .001), and renal dysfunction (41.5% versus 22.2%, P = .015) than those without CMBs. On multivariable analyses, renal dysfunction (odds ratio, 95% confidence interval; model 1: 2.38, 1.02-5.66; model 2: 2.78, 1.16-6.81), WMH (3.87, 1.76-8.80; 3.72, 1.64-8.71), SLI (3.85, 1.71-9.14; 4.20, 1.77-10.8), and diabetes mellitus (.26, .09-.63; .24, .08-.63) were independently associated with CMBs. CONCLUSIONS: In patients with ALI, renal dysfunction was positively associated with CMBs independent of cerebral SVD.

Risk of intracerebral hemorrhage after thrombolysis in patients with asymptomatic hemorrhage on T2*.

BACKGROUND: Intravenous thrombolysis using the tissue-type plasminogen activator (t-PA) is contraindicated for patients with a history of intracerebral hemorrhage (ICH). T2*-weighted magnetic resonance imaging (MRI) is able to detect asymptomatic ICH. If there is an association between asymptomatic ICH on T2* before t-PA therapy and ICH after t-PA therapy, we may be able to take preventive measures before starting t-PA therapy in patients with MRI-proven hemorrhage. The aim of the present study was to investigate whether asymptomatic ICH seen on T2* increases the risk of new ICH after t-PA therapy. METHODS: Patients who had consecutive stroke treated with t-PA between October 2005 and November 2013 were enrolled. A hypointense T2* signal with a diameter >5 mm was defined as asymptomatic ICH before t-PA therapy. The presence of new ICH at 24 h after t-PA therapy was assessed using T2*. Symptomatic ICH (sICH) was defined as new ICH combined with an increase in the National Institutes of Health Stroke Scale score ≥4. At 3 months after onset, good and poor outcomes were defined as modified Rankin Scale (mRS) scores of 0-1 and 4-6, respectively. RESULTS: Of 300 patients (age 77 [68-83] years; 173 [58%] males), 25 (8%) had an asymptomatic ICH on T2* before t-PA therapy. Eleven (45%) patients showed an isolated asymptomatic ICH. Three (12%) patients had a round hypointense lesion similar to microbleeds. Nine (36%) patients had a hemorrhagic transformation within a prior infarcted area. Multiple asymptomatic ICHs were seen in 2 (8%) patients. The rates of good and poor outcomes at 3 months were 24 and 59% of patients with asymptomatic ICH and 38 and 41% of patients without asymptomatic ICH (p = 0.300 and 0.202, respectively). At 24 h after t-PA therapy, 11 (44%) of the 25 patients with asymptomatic ICH before t-PA therapy and 87 (32%) of 275 without asymptomatic ICH had new ICH (p = 0.265). Only 1 (4%) of 25 patients with asymptomatic ICH before t-PA therapy and 6 (2%) of 275 without asymptomatic ICH had sICH within 24 h (p = 0.460). On multivariate logistic regression analysis, neither new ICH (odds, 1.19; 95% CI, 0.40-3.54, p = 0.753) nor sICH (odds, 0.95; 95% CI, 0.08-11.90, p = 0.970) was related to asymptomatic ICH on T2* before t-PA therapy. CONCLUSION: The presence of T2* hypointensity as a marker of asymptomatic ICH may not be associated with new ICH and sICH after t-PA therapy.

Brain natriuretic peptide upon admission as a biological marker of short-term mortality after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: The purpose of the present study was to test the hypothesis that plasma brain natriuretic peptide (BNP) is associated with short-term mortality after intracerebral hemorrhage (ICH). METHODS: We prospectively enrolled 271 patients (median age 72 years; 109 females) who were admitted within 24 h of ICH onset between April 2007 and July 2011 and in whom plasma BNP levels were measured upon admission. The patients were assigned to two groups according to survival within 1 month of ICH. Factors associated with mortality were determined by multivariate logistic regression analysis. RESULTS: Within 1 month of ICH, 48 (17.7%) of the 271 enrolled patients died. The median (interquartile range) level of plasma BNP was significantly higher in the group of non-survivors than in the group of survivors [102.5 (48.7-205.0) vs. 32.4 (17.3-85.0) pg/ml; p < 0.001]. A cutoff BNP level of 60.0 pg/ml could predict death within 1 month of ICH. Multivariate logistic regression analysis showed that a plasma BNP of >60.0 pg/ml (OR 4.7; 95% CI 1.43-15.63; p = 0.011) was independently associated with mortality within 1 month after ICH. CONCLUSIONS: A high BNP level upon admission is associated with mortality within 1 month after ICH.

Plasma brain natriuretic Peptide as a predictive marker of early recurrent stroke in cardioembolic stroke patients.

BACKGROUND: Whether brain natriuretic peptide (BNP) levels are associated with early recurrent stroke in cardioembolic stroke patients was investigated. METHODS: From January 2010 to March 2014, consecutive patients within 24 hours of onset of cardioembolic stroke were prospectively enrolled, and admission plasma BNP levels were measured. Recurrent stroke was identified as the occurrence of additional neurologic deficits and the appearance of a new infarct on neuroimaging. Patients were divided into 2 groups: the recurrence group and the nonrecurrence group. Factors associated with stroke recurrence were investigated by multiple logistic regression analysis. RESULTS: A total of 348 patients were included; 17 patients (5%) had recurrent stroke during hospitalization. The median interval from stroke onset to recurrent stroke was 4 days (range, 0-30). BNP levels were significantly higher in the recurrence group than in the nonrecurrence group (304.1 vs. 206.5 pg/mL, P = .029). The optimal cutoff level, sensitivity, and specificity of BNP levels to distinguish the recurrence group from the nonrecurrence group were 255.0 pg/mL, 76%, and 60%, respectively. On multivariate analysis after adjustment for confounders, plasma BNP ≥ 255.0 pg/mL (odds ratio, 5.21; 95% confidence interval, 1.63-16.72; P = .005) was independently associated with recurrent stroke during hospitalization in cardioembolic stroke patients. CONCLUSIONS: Plasma BNP could be a useful marker for predicting early recurrent stroke during hospitalization in cardioembolic stroke patients.

High pulse wave velocity is associated with enlarged perivascular spaces in dementia with Lewy bodies.

Previous studies have demonstrated associations between enlarged perivascular spaces (EPVS) and dementias such as Alzheimer's disease. However, an association between EPVS and dementia with Lewy bodies (DLB) has not yet been clarified. We performed a cross-sectional analysis of our prospective study cohort of 109 participants (16 with DLB). We assessed cognitive function, pulse wave velocity (PWV), and brain magnetic resonance imaging features. The relationships between EPVS and DLB were evaluated using multivariable logistic regression analyses. Compared with the non-dementia group, the DLB group was more likely to have EPVS in the basal ganglia. Compared with participants without EPVS, those with EPVS were older and had cognitive impairment and high PWV. In multivariable analyses, EPVS in the basal ganglia was independently associated with DLB. High PWV was also independently associated with EPVS in both the basal ganglia and centrum semiovale. High PWV may cause cerebrovascular pulsatility, leading to accelerated EPVS in DLB participants.

Enlarged Perivascular Spaces Are Independently Associated with High Pulse Wave Velocity: A Cross-Sectional Study.

Background: Recent studies have demonstrated an association between pulse wave velocity (PWV), cerebral small vessel disease (SVD), and cognitive impairment such as Alzheimer's disease. However, the association between brachial-ankle PWV and enlarged perivascular spaces (EPVS), one component of cerebral SVD remains controversial. Objective: To investigate the relationship between brachial-ankle PWV and EPVS severity in participants without dementia. Methods: We performed a cross-sectional study of data of 74 participants from sub-analysis of ongoing research. We assessed cognitive function, brachial-ankle PWV, and brain magnetic resonance imaging (MRI) features. Using brain MRI, EPVS were separately assessed as basal ganglia (BG)-EPVS or centrum semiovale (CSO)-EPVS on the basis of their location. The relationship between EPVS severity and brachial-ankle PWV was evaluated using multivariable ordinal logistic regression analyses. Results: We analyzed 74 participants (women: 47%, mean age: 73 years, mild cognitive impairment [MCI]: 74%). Compared with participants with normal cognition, those with MCI were more likely to have both severe BG-EPVS and severe CSO-EPVS. In multivariable analyses, high brachial-ankle PWV and age were independently associated with BG-EPVS severity (odds ratio [95% confidence interval]: 1.19 [1.02-1.38], 1.09 [1.01-1.17], respectively), whereas only age was independently associated with CSO-EPVS severity. A causal mediation analysis under a counterfactual approach revealed a significant pure natural indirect effect of brachial-ankle PWV on MCI that was mediated by BG-EPVS (estimate: 1.04, 95% CI: 1.01-1.12, p = 0.006). Conclusions: Brachial-ankle PWV was associated with BG-EPVS severity. High PWV may cause cerebrovascular pulsatility, which accelerates BG-EPVS and may worsen cognitive impairment.

Association between abdominal adiposity and cognitive decline in older adults: a 10-year community-based study.

OBJECTIVES: This study aimed to investigate the association between abdominal adiposity and change in cognitive function in community-dwelling older adults. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal study included older adults aged ≥60 years without cognitive impairment who participated in the National Institute for Longevity Sciences - Longitudinal Study of Aging. MEASUREMENTS: Cognitive function was evaluated biennially using the Mini-Mental State Examination (MMSE) over 10 years. Waist circumference (WC) was measured at the naval level, and subcutaneous fat area (SFA) and visceral fat area (VFA) were assessed using baseline computed tomography scans. WC, SFA, and VFA areas were stratified into sex-adjusted tertiles. A linear mixed model was applied separately for men and women. RESULTS: This study included 873 older adults. In men, the groups with the highest levels of WC, SFA, and VFA exhibited a greater decline in MMSE score than the groups with the lowest levels (ß [95% confidence interval]: WC, -0.12 [-0.23 to -0.01]; SFA, -0.13 [-0.24 to -0.02]; VFA, -0.11 [-0.22 to -0.01]). In women, the group with the highest level of WC and SFA showed a greater decline in MMSE score than the group with the lowest level (WC, -0.12 [-0.25 to -0.01]; SFA, -0.18 [-0.30 to -0.06]), but VFA was not associated with cognitive decline. CONCLUSION: Higher WC, SFA, and VFA in men and higher WC and SFA in women were identified as risk factors for cognitive decline in later life, suggesting that abdominal adiposity involved in cognitive decline may differ according to sex.

New appearance of extraischemic microbleeds on T2*-weighted magnetic resonance imaging 24 hours after tissue-type plasminogen activator administration.

BACKGROUND AND PURPOSE: It is unknown whether new-extraischemic microbleeds (new-EMBs) develop rapidly after tissue-type plasminogen activator (tPA) infusion. We hypothesized that new-EMBs may develop rapidly after tPA infusion using T2*-weighted MRI (T2*) and investigated the frequency and clinical factors associated with new-EMBs. METHODS: Patients with acute stroke within 3 hours of onset who were treated with tissue-type plasminogen activator (tPA) were studied prospectively. T2* was performed before and 24 hours after tPA therapy. Independent clinical factors associated with new-EMBs development were examined using multivariate logistic regression analysis. RESULTS: A total of 224 patients (121 men; mean age, 76.2±10.6 years) were enrolled in the present study. MBs before tPA infusion were observed in 72 (32.1%) patients. Within 24 hours after tPA infusion, 6 (2.7%) patients had symptomatic intracranial hemorrhage (extraischemic [n=4], and hemorrhagic transformation [n=2]). Follow-up T2* revealed asymptomatic new-EMBs in 11 (4.9%) patients and hemorrhagic transformation in the infarcted area in 65 (29.0%). The total and mean number of new-EMBs were 23 and 1.6±1.3, respectively. Patients with new-EMBs more frequently had symptomatic extraischemic hemorrhage than those without new-EMBs (27.3% [3/11] versus 0.5% [1/213]; P=0.0003). However, the frequency of hemorrhagic transformation was not different between patients with and without new-EMBs (27.3% versus 29.1%; P=0.9999). Multivariate logistic regression demonstrated that the presence of MBs before tPA infusion was the only independent factor associated with new-EMBs (odds ratio, 10.6; 95% confidence interval, 20.68-54.279; P=0.0046). CONCLUSIONS: New-EMBs occurred rapidly after tPA infusion in 4.9% of patients. The presence of MBs before tPA therapy was associated with new-EMBs. Patients with new-EMBs are likely to have symptomatic extraischemic hemorrhage.

Brain natriuretic peptide on admission as a biological marker of long-term mortality in ischemic stroke survivors.

BACKGROUND AND PURPOSE: We investigated whether brain natriuretic peptide (BNP) can serve as a biological marker of long-term mortality in ischemic stroke survivors. METHODS: Consecutive patients with ischemic stroke within 24 h of onset from April 2007 to December 2010 were prospectively enrolled, and admission plasma BNP levels were measured. Survivors were followed up until 1 year after stroke onset. Patients were divided into two groups: the deceased group and the surviving group. The factors associated with long-term mortality were investigated by multiple logistic regression analysis. RESULTS: A total of 736 patients who were alive at hospital discharge were included; 130 (17.7%) patients died. On multivariate analysis, age>75 years (odds ratio, OR, 2.83; 95% CI, 1.74-4.60, p=0.0001), dialysis-dependent chronic renal failure (OR, 5.99; 95% CI, 2.18-16.47, p=0.0005), modified Rankin Scale score>3 at discharge (OR, 4.41; 95% CI, 2.76-7.05, p<0.0001), and plasma BNP>100.0 pg/ml (OR, 3.94; 95% CI, 2.31-6.73, p<0.0001) were found to be independently associated with long-term mortality. We developed a risk score from 4 variables (each variable: 1 point, total score: 0-4 points). The mortality rates were 2% with a score of 0, 9% with a score of 1, 27% with a score of 2 and 50% with a score≥3. CONCLUSIONS: The risk score, composed of clinical parameters and BNP, may predict long-term mortality in ischemic stroke survivors.