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OBJECTIVES: Intracerebral hemorrhage (ICH) and cerebral microbleeds (CMB) in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy are more common in East Asian populations than in people of white European ancestry. We hypothesized that the ethnic difference is explained by the East Asian-specific NOTCH3 p.R75P mutation. METHODS: This retrospective observational study included 118 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in Japanese and Korean cohorts. We investigated whether the p.R75P mutation is associated with symptomatic ICH and multiple CMB (>5) using quasi-Poisson regression models. We predicted the NOTCH3 extracellular domain protein structures in silico and graded NOTCH3 extracellular domain immunostaining in skin vessels of some patients, with subsequent comparisons between p.R75P and other conventional mutations. RESULTS: Among 63 Japanese patients (median age 55 years; 56% men), 15 had a p.R75P mutation, significantly associated with symptomatic ICH (adjusted relative risk 9.56, 95% CI 2.45-37.31), multiple CMB (3.00, 1.34-6.71), and absence of temporopolar lesions (4.91, 2.29-10.52) after adjustment for age, sex, hypertension, and antithrombotics. In the Korean cohort (n = 55; median age 55 years; 51% men), the p.R75P mutation (n = 13) was also associated with symptomatic ICH (8.11, 1.83-35.89), multiple CMB (1.90, 1.01-3.56), and absence of temporopolar lesions (2.32, 1.08-4.97). Structural analysis revealed solvent-exposed free cysteine thiols in conventional mutations, directly causing aggregation, whereas a stereochemically incompatible proline residue structure in p.R75P lowers correct disulfide bond formation probability, indirectly causing aggregation. Pathologically, the p.R75P mutation resulted in less vascular NOTCH3 extracellular domain accumulation than the other conventional mutations. INTERPRETATION: NOTCH3 p.R75P mutation is associated with hemorrhagic presentations, milder temporopolar lesions, and distinct mutant protein structure properties. ANN NEUROL 2024;95:1040-1054.
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CADASIL , Hemorragia Cerebral , Mutación , Receptor Notch3 , Humanos , Masculino , Femenino , Receptor Notch3/genética , Persona de Mediana Edad , CADASIL/genética , Estudios Retrospectivos , Hemorragia Cerebral/genética , Anciano , Mutación/genética , Adulto , Japón , República de Corea , Pueblo Asiatico/genéticaRESUMEN
OBJECTIVE: To assess whether post-stroke epilepsy (PSE) is associated with neuroimaging findings of hemosiderin in a case-control study, and whether the addition of hemosiderin markers improves the risk stratification models of PSE. METHODS: We performed a post-hoc analysis of the PROgnosis of POST-Stroke Epilepsy study enrolling PSE patients at National Cerebral and Cardiovascular Center, Osaka, Japan, from November 2014 to September 2019. PSE was diagnosed when one unprovoked seizure was experienced >7 days after the index stroke, as proposed by the International League Against Epilepsy. As controls, consecutive acute stroke patients with no history or absence of any late seizure or continuing antiseizure medications at least 3 months after stroke were retrospectively enrolled during the same study period. We examined cortical microbleeds and cortical superficial siderosis (cSS) using gradient-echo T2*-weighted images. A logistic regression model with ridge penalties was tuned using 10-fold cross-validation. We added the item of cSS to the existing models (SeLECT and CAVE) for predicting PSE and evaluated performance of new models. RESULTS: The study included 180 patients with PSE (67 women; median age 74 years) and 1,183 controls (440 women; median age 74 years). The cSS frequency was higher in PSE than control groups (48.9% vs 5.7%, p < 0.0001). Compared with the existing models, the new models with cSS (SeLECT-S and CAVE-S) demonstrated significantly better predictive performance of PSE (net reclassification improvement 0.63 [p = 0.004] for SeLECT-S and 0.88 [p = 0.001] for CAVE-S at the testing data). INTERPRETATION: Cortical superficial siderosis was associated with PSE, stratifying stroke survivors at high risk of PSE. ANN NEUROL 2023;93:357-370.
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Epilepsia , Siderosis , Accidente Cerebrovascular , Anciano , Femenino , Humanos , Estudios de Casos y Controles , Epilepsia/complicaciones , Hemosiderina , Estudios Retrospectivos , Convulsiones/complicaciones , Siderosis/complicaciones , Siderosis/diagnóstico por imagen , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , MasculinoRESUMEN
OBJECTIVE: Postseizure functional decline is a concern in poststroke epilepsy (PSE). However, data on electroencephalogram (EEG) markers associated with functional decline are scarce. Thus, we investigated whether periodic discharges (PDs) and their specific characteristics are associated with functional decline in patients with PSE. METHODS: In this observational study, patients admitted with seizures of PSE and who had scalp EEGs were included. The association between the presence or absence of PDs and postseizure short-term functional decline lasting 7 days after admission was investigated. In patients with PD, EEG markers were explored for risk stratification of short-term functional decline, according to the American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology. The association between EEG markers and imaging findings and long-term functional decline at discharge and 6 months after discharge, defined as an increase in the modified Rankin Scale score compared with the baseline, was evaluated. RESULTS: In this study, 307 patients with PSE (median age = 75 years, range = 35-97 years, 64% males; hemorrhagic stroke, 47%) were enrolled. Compared with 247 patients without PDs, 60 patients with PDs were more likely to have short-term functional decline (12 [20%] vs. 8 [3.2%], p < .001), with an adjusted odds ratio (OR) of 4.26 (95% confidence interval [CI] = 1.44-12.6, p = .009). Patients with superimposed fast-activity PDs (PDs+F) had significantly more localized (rather than widespread) lesions (87% vs. 58%, p = .003), prolonged hyperperfusion (100% vs. 62%, p = .023), and a significantly higher risk of short-term functional decline than those with PDs without fast activity (adjusted OR = 22.0, 95% CI = 1.87-259.4, p = .014). Six months after discharge, PDs+F were significantly associated with long-term functional decline (adjusted OR = 4.21, 95% CI = 1.27-13.88, p = .018). SIGNIFICANCE: In PSE, PDs+F are associated with sustained neuronal excitation and hyperperfusion, which may be a predictor of postseizure short- and long-term functional decline.
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Epilepsia , Alta del Paciente , Masculino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Convulsiones , Electroencefalografía , HospitalizaciónRESUMEN
OBJECTIVE: Motivated by the challenges raised by diagnosing poststroke epilepsy (PSE), especially in nonmotor onset seizure (non-MOS), we aimed to investigate the features of non-MOS, including seizure sequences, patient characteristics, and electrophysiological and imaging findings in PSE. METHODS: This observational cohort study enrolled patients with PSE whose seizure onset was witnessed. According to the International League Against Epilepsy (ILAE) 2017 seizure classification, we classified seizure-onset symptoms into the non-MOS and MOS groups. We compared the different clinical characteristics between the two groups. RESULTS: Between 2011 and 2018, we enrolled 225 patients with PSE (median age, 75 years), consisting of 97 (43%) with non-MOS and 128 (57%) with MOS. Overall, 65 (67%) of the patients without MOS had no subsequent convulsions. Multivariable logistic regression analysis showed significant associations of non-MOS with absence of poststroke hemiparesis (adjusted odds ratio [OR], 1.88; 95% confidence interval [CI], 1.03-3.42), frontal stroke lobe lesions (OR, 2.11; 95% CI, 1.14-3.91), and putaminal stroke lesions (OR, 2.51; 95% CI, 1.22-5.18) as negative indicators. Postictal single-photon emission computed tomography (SPECT) detected prolonged hyperperfusion in the temporal lobe more frequently in the non-MOS than in the MOS group (48% vs 31%; p = .02). The detection rate was higher than spikes/sharp waves in scalp electroencephalography, both in the non-MOS group (72% vs 33%; p < .001) and the MOS group (68% vs 29%; p < .001). SIGNIFICANCE: This study provides the clinical features of non-MOS in patients with PSE. Compared with the patients with MOS, patients with non-MOS showed less likely subsequent convulsive seizures, highlighting the clinical challenges. Postictal perfusion imaging and negative indicators of the non-MOS type may help diagnose and stratify PSE.
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Epilepsia , Accidente Cerebrovascular , Anciano , Electroencefalografía/métodos , Epilepsia/diagnóstico por imagen , Epilepsia/etiología , Humanos , Convulsiones/diagnóstico por imagen , Convulsiones/etiología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
OBJECTIVES: Wandering behavior is one of the most troublesome behavioral disturbances in dementia. Inconsistent associations between physical function and wandering behavior were reported, and the effect of cognitive decline may be different according to walking ability. The purposes of this study are to investigate whether high walking ability is a risk factor for wandering behavior and to investigate the interaction of walking ability and cognitive function with wandering behavior in older adults with dementia. METHODS: This retrospective cohort study included 3979 elderly adults with dementia. The association of cognitive function and walking ability with incidence of wandering behavior during a 5-year follow-up period were examined using a generalized linear model, and relative excess risk due to interaction (RERI) was calculated. RESULTS: Severe cognitive decline and high walking ability were associated with a higher risk for wandering behavior. Additionally, some joint effects of cognitive decline and walking ability decline were higher than the sum of its individual effects (RERI [95% confidence interval], severe cognitive decline × 'walk with help': 1.58 [0.35, 2.81]; severe cognitive decline × 'independent': 3.09 [1.05, 5.14]). CONCLUSIONS: Effects of cognitive decline and walking ability on incidence of wandering behavior were observed, and the effects varied depending on their combination.
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Disfunción Cognitiva , Demencia , Conducta Errante , Anciano , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Estudios de Cohortes , Demencia/psicología , Humanos , Incidencia , Estudios Retrospectivos , Caminata/psicologíaRESUMEN
AIMS: To evaluate the prognostic impact of fragmented QRS (fQRS) on idiopathic dilated cardiomyopathy (DCM). METHODS AND RESULTS: We conducted a prospective observational study of 290 consecutive patients with DCM (left ventricular ejection fraction ≤ 40%) and narrow QRS who underwent cardiac magnetic resonance. We defined fQRS as the presence of various RSR' patterns in ≥2 contiguous leads representing the anterior (V1-V5), inferior (II, III, and aVF), or lateral (I, aVL, and V6) myocardial segments. Multiple fQRS was defined as the presence of fQRS in ≥2 myocardial segments. Patients were divided into three groups: no fQRS, single fQRS, or multiple fQRS. The primary endpoint was a composite of hard cardiac events consisting of heart failure death, sudden cardiac death (SCD), or aborted SCD. The secondary endpoints were all-cause death and arrhythmic event. During a median follow-up of 3.8 years (interquartile range, 1.8-6.2), 31 (11%) patients experienced hard cardiac events. Kaplan-Meier analysis showed that the rates of hard cardiac events and all-cause death were similar in the single-fQRS and no-fQRS groups and higher in the multiple-fQRS group (P = 0.004 and P = 0.017, respectively). Multivariable Cox regression identified that multiple fQRS is a significant predictor of hard cardiac events (hazard ratio, 2.23; 95% confidence interval, 1.07-4.62; P = 0.032). The multiple-fQRS group had the highest prevalence of a diffuse late gadolinium enhancement pattern (no fQRS, 21%; single fQRS, 22%; multiple fQRS, 39%; P < 0.001). CONCLUSION: Multiple fQRS, but not single fQRS, is associated with future hard cardiac events in patients with DCM.
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Cardiomiopatía Dilatada , Cardiomiopatía Dilatada/diagnóstico , Medios de Contraste , Electrocardiografía , Gadolinio , Humanos , Pronóstico , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Dementia-related missing and subsequent deaths are becoming serious problems with increases in people with dementia. However, there are no sufficient studies investigating the incidence rate, the mortality rate, and their risk factors. METHODS: An ecological study aggregated at the Japanese prefectural level was conducted. Dementia-related missing persons cases and deaths in 2018 were extracted from the statistics of the National Police Agency in Japan. We extracted variables about older adults' characteristics, care, and safety as candidate variables considered to be relevant to dementia-related missing persons cases and deaths. Associations of the candidate variables with the incidence and mortality rates were analyzed using the generalized linear model (family: quasi-poisson, link: log) adjusted for confounding factors (proportion of older adults and gross prefectural product). RESULTS: The incidence rate and mortality rate per 100,000 person-year was 21.72 and 0.652 in Japan, respectively. One facility increase in the number of nursing care facilities for older adults per 100,000 persons aged 65-years-old or more was associated with a 7.9% (95% confidence interval [CI], 3.3-12.4%) decrease in the incidence rate. One increase in the number of public health nurses per 100,000 persons was associated with a 3.2% (95% CI, 1.6-4.9%) decrease in the incidence rate. A ten percent increase in the proportion of people who live in an urban area was associated with a 20.3% (95% CI, 8.7-33.2%) increase in the incidence rate and a 12.9% (95% CI, 5.6-19.8%) decrease in the mortality rate. CONCLUSIONS: Identified associated factors may be useful for managing or predicting dementia-related missing persons cases and associated deaths.
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Demencia/epidemiología , Demencia/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Demencia/psicología , Femenino , Humanos , Incidencia , Japón/epidemiología , Masculino , Persona de Mediana Edad , Policia , Factores de Riesgo , Conducta ErranteRESUMEN
In-home monitoring systems have been used to detect cognitive decline in older adults by allowing continuous monitoring of routine activities. In this study, we investigated whether unobtrusive in-house power monitoring technologies could be used to predict cognitive impairment. A total of 94 older adults aged ≥65 years were enrolled in this study. Generalized linear mixed models with subject-specific random intercepts were used to evaluate differences in the usage time of home appliances between people with and without cognitive impairment. Three independent power monitoring parameters representing activity behavior were found to be associated with cognitive impairment. Representative values of mean differences between those with cognitive impairment relative to those without were -13.5 min for induction heating in the spring, -1.80 min for microwave oven in the winter, and -0.82 h for air conditioner in the winter. We developed two prediction models for cognitive impairment, one with power monitoring data and the other without, and found that the former had better predictive ability (accuracy, 0.82; sensitivity, 0.48; specificity, 0.96) compared to the latter (accuracy, 0.76; sensitivity, 0.30; specificity, 0.95). In summary, in-house power monitoring technologies can be used to detect cognitive impairment.
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Disfunción Cognitiva , Anciano , Inteligencia Artificial , Disfunción Cognitiva/diagnóstico , Computadores , Humanos , Modelos LinealesRESUMEN
Vascular risk factors, such as type 2 diabetes mellitus (T2DM), are associated with the increased risk of Alzheimer's disease. One of the common T2DM medications, dipeptidyl peptidase (DPP)-4 inhibitors, have a minimum risk for hypoglycemia and have recently been suggested to ameliorate ß-amyloid pathology. However, conflicting results have been reported regarding the effects of DPP-4 inhibition on cognitive function and tau pathology. Thus, we investigated whether inhibiting DPP-4 affects tau pathology and cognition in a mouse model of tauopathy with hyperglycemia. Male mice overexpressing the P301S mutant human microtubule-associated protein tau gene (PS19) were fed either a low or high-fat diet. PS19 mice were then administered either linagliptin, a DPP-4 inhibitor, or vehicle, from 6 weeks to 8 months of age. Linagliptin-treated mice exhibited higher levels of glucagon-like peptide-1 and decreased fasting blood glucose, compared with the vehicle-treated mice at 8 months. Linagliptin treatment significantly restored spatial reference memory and increased cerebral blood flow without affecting phosphorylation levels of tau or endothelial nitric oxide synthase (eNOS) in the brain. Linagliptin may ameliorate HFD-induced cognitive worsening in tauopathy, at least partially, by increasing cerebral perfusion via the eNOS-independent pathway.
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Disfunción Cognitiva/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Linagliptina/uso terapéutico , Tauopatías/tratamiento farmacológico , Animales , Disfunción Cognitiva/etiología , Disfunción Cognitiva/patología , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Humanos , Hiperglucemia/complicaciones , Hiperglucemia/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Tauopatías/complicaciones , Tauopatías/patologíaRESUMEN
INTRODUCTION: National-level data on trends in the prognosis of age-stratified patients with intracerebral hemorrhage (ICH) are lacking. This study aimed to assess time trends in in-hospital mortality and functional outcomes of ICH patients by sex and age, and to explore factors associated with changes in in-hospital mortality trend. PATIENTS AND METHODS: Using the largest nationwide, J-ASPECT stroke database in Japan, this serial cross-sectional study included ICH patients aged ⩾18 years who were hospitalized for non-traumatic ICH from April 2010 to March 2020. We examined trends in in-hospital mortality and functional outcomes using the modified Rankin Scale at discharge, as well as differences in in-hospital mortality change between age groups. RESULTS: Among 262,399 ICH patients from 934 hospitals, crude in-hospital mortality showed a significant decreasing time trend (from 19.5% to 16.7%), and this trend was consistent across sex and age groups. In addition, differences in in-hospital mortality change over the 10-year study period were significant between male patients aged ⩾75 years and those aged ⩽64 years (-3.9% [95% confidence interval, -5.4 to -2.4] for 75-84 years; -4.1% [-6.3 to -1.9] for ⩾85 years). On the other hand, the proportion of dependent patients (mRS 3-5) at discharge increased from 52.0% to 54.9% over the 10-year study period. CONCLUSION: The in-hospital mortality of ICH patients improved, whereas the proportion of patients with dependent functional outcome at discharge increased, over the 10-year study period. Elucidating the mechanism underlying differences in in-hospital mortality reduction in men may provide insights into effective interventions in the future.
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Hemorragia Cerebral , Mortalidad Hospitalaria , Humanos , Mortalidad Hospitalaria/tendencias , Japón/epidemiología , Masculino , Anciano , Femenino , Hemorragia Cerebral/mortalidad , Persona de Mediana Edad , Anciano de 80 o más Años , Estudios Transversales , Factores de Edad , Adulto , Bases de Datos Factuales , Factores SexualesRESUMEN
Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common form of hereditary cerebral small vessel disease (SVD), currently lacks disease-modifying treatments. Adrenomedullin (AM), a vasoactive peptide with angiogenic, vasodilatory, anti-inflammatory, and anti-oxidative properties, shows potential effects on the neuro-glial-vascular unit. Objective: The AdrenoMedullin for CADASIL (AMCAD) study aims to assess the efficacy and safety of AM in patients with CADASIL. Sample size: Overall, 60 patients will be recruited. Methods: The AMCAD is a multicenter, investigator-initiated, single-arm phase II trial. Patients with a confirmed CADASIL diagnosis, based on NOTCH3 genetic testing, will receive an 8-h AM treatment (15 ng/kg/min) for 14 days following a baseline assessment (from day 1 to day 14). Follow-up evaluations will be performed on days 15, 28, 90, and 180. Study outcomes: The primary endpoint is the cerebral blood flow change rate in the frontal cortex, evaluated using arterial spin labeling magnetic resonance imaging, from baseline to day 28. Summary statistics, 95% confidence intervals, and a one-sample t-test will be used for analysis. Conclusion: The AMCAD study aims to represent the therapeutic potential of AM in patients with CADASIL, addressing an unmet medical need in this challenging condition. Clinical Trial Registration: jRCT 2,051,210,117 (https://jrct.niph.go.jp/en-latest-detail/jRCT2051210117).
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BACKGROUND: The development of numerous disease-modifying drugs for age-related dementia has been attempted based on the amyloid-ß (Aß) hypothesis without much success. Taxifolin (TAX), a natural bioactive flavonoid, shows pleiotropic neuroprotective effects with inhibition of Aß aggregation, production, and glycation, antiinflammatory effects, and amelioration of the waste clearance system. We hypothesized that TAX intake is associated with the suppression of cognitive deterioration. OBJECTIVE: To investigate associations between TAX intake and cognitive changes. METHODS: We retrospectively identified patients who orally took TAX 300âmg/day and regularly underwent Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog) and Montreal Cognitive Assessment (MoCA) and compared the temporal changes in ADAS-Cog and MoCA between the non-treatment (pre-TAX) period (180±100 days) and following treatment (on-TAX) period (180±100 days) from June 2020 to November 2021. Since some additional patients underwent the Mini-Mental State Examination (MMSE) instead of the MoCA at the beginning of the pre-TAX period, the same comparison was performed using the MoCA total score converted from MMSE as a sensitivity analysis. RESULTS: Sixteen patients were identified. TAX intake was associated with significantly higher interval changes in the MoCA subscale scores of visuospatial/executive function (pâ=â0.016), verbal fluency (pâ=â0.02), and the total score (pâ=â0.034), but not with ADAS-Cog (total score, pâ=â0.27). In the sensitivity analysis, 29 patients were included. TAX intake was associated with a significantly higher interval change in the total MoCA score (pâ=â0.004) but not with ADAS-Cog (pâ=â0.41). CONCLUSION: Our findings provide a basis for TAX as a novel strategy for maintaining brain health during aging. A prospective cohort study is required to confirm these findings.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Demencia , Humanos , Enfermedad de Alzheimer/psicología , Estudios Prospectivos , Estudios Retrospectivos , Pruebas Neuropsicológicas , Demencia/psicología , Disfunción Cognitiva/psicología , Péptidos beta-Amiloides/farmacología , CogniciónRESUMEN
Background: The RNF213 p.R4810K variant is associated with moyamoya disease in East Asian individuals and increases the risk of developing intracranial major artery stenosis/occlusion (ICASO) that affects anterior circulation. Meanwhile, 0.5% to 2.5% of asymptomatic East Asian individuals also carry this variant. As such, additional factors are likely required to develop ICASO in variant carriers. Familial hypercholesterolemia (FH) is a common genetic disorder in Japan that has a significant associated risk of developing premature coronary atherosclerosis; however, the relationship between ICASO and FH remains unknown. Objectives: This study aimed to determine if FH facilitates RNF213 p.R4810K carriers to develop ICASO. Methods: We enrolled patients with FH who had undergone brain magnetic resonance angiography at our hospital from May 2005 to March 2020. The RNF213 p.R4810K variant, and LDLR and PCSK9 mutations were genotyped. ICASO lesions in the brain magnetic resonance angiogram were analyzed. Results: Six RNF213 p.R4810K variant carriers were identified among 167 patients with FH (LDLR, n = 104; PCSK9, n = 22). Five of the carriers (83.3%) exhibited ICASO in the anterior circulation; a significant difference in ICASO frequency was observed between the variant carriers and noncarriers (P = 0.025). The median number of stenotic or occluded arteries in the anterior circulation was also significantly larger in the variant carriers (3 vs 1, P = 0.01); however, did not differ between patients with FH with LDLR and PCSK9 mutations. Conclusions: Patients with FH exhibit increased prevalence and severity of ICASO associated with RNF213 p.R4810K. Gene mutations for FH may confer an increased risk of ICASO in RNF213 p.R4810K carriers.
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BACKGROUND & AIMS: This study aimed to investigate the associations of pre-existing sarcopenia with swallowing function, oral intake level, and aspiration pneumonia in patients with acute stroke. METHODS: This observational study included patients (≥60 years of age) with acute ischemic stroke or intracerebral hemorrhage within 7 days of onset who were screened for sarcopenia, malnutrition, and swallowing difficulties in a stroke-care unit within 48 h of admission. Sarcopenia was defined by the Asian Working Group on Sarcopenia 2019 as having a low calf circumference, handgrip strength, and appendicular muscle mass index. The primary outcome was impaired oral intake (functional oral intake scale <5 points) at 3, 7, and 14 days after admission, and the secondary outcome was aspiration pneumonia during hospitalization. RESULTS: We enrolled 350 patients (median age of 77 years; 63% males) who underwent the aforementioned screening. Sarcopenia was diagnosed in 34% of patients, and malnutrition was found in 66% of patients with sarcopenia. When compared with the comparison group (defined as patients with either or both normal calf circumference and handgrip strength), the sarcopenia group had significantly lower tongue pressure and a higher prevalence of dysphagia. Sarcopenia was associated with functional oral intake scale <5 at 7 days (adjusted odds ratio [OR], 4.72; 95% confidence interval [CI], 1.91-11.71); p = 0.002) and 14 days (adjusted OR, 3.93; 95% CI, 1.47-10.53; p = 0.006) and with aspiration pneumonia during hospitalization (adjusted OR, 6.12; 95% CI, 1.63-22.94; p = 0.007). CONCLUSION: Acute stroke patients with sarcopenia may have weakness of the swallowing-related muscles which may lead to impaired oral intake and aspiration pneumonia.
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Trastornos de Deglución , Accidente Cerebrovascular Isquémico , Desnutrición , Neumonía por Aspiración , Sarcopenia , Accidente Cerebrovascular , Anciano , Femenino , Humanos , Masculino , Deglución , Trastornos de Deglución/epidemiología , Trastornos de Deglución/etiología , Trastornos de Deglución/diagnóstico , Fuerza de la Mano , Accidente Cerebrovascular Isquémico/complicaciones , Desnutrición/complicaciones , Desnutrición/epidemiología , Neumonía por Aspiración/etiología , Neumonía por Aspiración/complicaciones , Presión , Sarcopenia/etiología , Sarcopenia/complicaciones , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/epidemiología , Lengua , Persona de Mediana Edad , Anciano de 80 o más AñosRESUMEN
AIMS: We aimed to determine the association between acute platelet reactivity and clinical outcome in acute ischemic stroke (AIS) or transient ischemic attack (TIA) with large-artery atherosclerosis (LAA). METHODS: In this prospective, 16-multicenter study, we enrolled AIS/TIA patients with LAA receiving clopidogrel. We assessed the association of P2Y12 reaction units (PRU) 24 hours after initiation of antiplatelets with the CYP2C19 genotype and recurrent ischemic stroke within 90 days, and the difference between acute (≤ 7 days) and subacute (8-90 days) phases. RESULTS: Among the 230 AIS/TIA patients enrolled, 225 with complete outcome data and 194 with genetic results were analyzed. A higher PRU was significantly associated with recurrent ischemic stroke within 90 days (frequency, 16%), and within 7 days (10%). Twenty-nine patients (15%) belonged to a CYP2C19 poor metabolizer group (CYP2C19ï¼2/ï¼2, ï¼2/ï¼3, or ï¼3/ï¼3). Multivariable receiver-operating characteristic analysis showed a greater area-under-the-curve (AUC) in predicting recurrence within 7 days, compared to 8-90 days (AUC, 0.79 versus 0.64; p=0.07), with a cut-off PRU of 254. Multivariable analysis showed high PRU (≥ 254), which had a comparable predictive performance for recurrent ischemic stroke within 7 days (odds ratio, 6.82; 95% CI, 2.23-20.9; pï¼0.001) to the CYP2C19 poor metabolizer genotype. The net reclassification improvement, calculated by adding high PRU (≥ 254) to a model including the CYP2C19 poor metabolizer genotype in the prediction of recurrence within 7 days, was 0.83 (pï¼0.001). CONCLUSIONS: Acute PRU evaluation possesses predictive value for recurrent ischemic stroke, especially within 7 days in AIS/TIA with LAA.
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Aterosclerosis , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Prospectivos , Ticlopidina , Citocromo P-450 CYP2C19/genética , Resultado del Tratamiento , Accidente Cerebrovascular/genética , Aterosclerosis/genéticaRESUMEN
Background: Acute aortic dissection (AAD) often leads to out-of-hospital cardiac arrest (OHCA) and death before hospital arrival. Objectives: The purpose of this study was to investigate differences in AAD incidence by sex. Methods: A population-based study in a city with 121,180 residents was conducted using postmortem computed tomography data to identify patients with AAD who died before hospital arrival in 2008-2020. The incidence rate ratio and odds ratio were estimated using Poisson regression and univariable logistic regression, respectively. Results: A total of 266 patients with incident AAD were enrolled: 84 patients with OHCA, 137 women [n = 137], and 164 patients with type A AAD. The crude and age-adjusted incidence of AAD was 16.2 and 14.3/100,000 person-years, respectively. The incidence of AAD was comparable by sex (men, 16.7/100,000 person-years; women, 15.7/100,000 person-years; incidence rate ratio: 0.94; 95% CI: 0.74-1.20; P = 0.64). Compared with men with AAD, women with AAD were older (77 ± 11 years vs 70 ± 14 years; P < 0.001), and a higher proportion had type A AAD (76% vs 47%; P < 0.001). Women with AAD had higher prehospital mortality than men with AAD (37% vs 21%; P = 0.004; OR: 2.24; 95% CI: 1.30-3.87; P = 0.004). Among 1,373 patients with OHCA, the proportion of women with AAD was significantly higher than the proportion of men with AAD (11% vs 3.9%; P < 0.001; OR: 2.90; 95% CI: 1.86-4.53; P < 0.001). AAD was most common in women aged 60 to 69 years (16.4%). Conclusions: Women had a higher incidence of AAD presenting as prehospital death than men.
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Importance: Chronic hemodynamically significant aortic regurgitation (AR) is associated with excess risk of death, yet data for Asian patients are lacking, and whether Asian patients can abide by Western guidelines as to when aortic valve surgery should be performed is unknown. Objective: To assess AR presentation and cutoffs of left ventricular ejection fraction (LVEF), LV end-systolic dimension index (LVESDi), and LV end-systolic volume index (LVESVi) that are associated with risk of death in Asian patients with AR. Design, Setting, and Participants: This retrospective cohort study included consecutive patients with chronic, moderately severe to severe AR from 3 tertiary referral centers (2 in Japan and 1 in Taiwan) from June 11, 2008, through November 19, 2020, with follow-up through November 11, 2021. Exposures: Aortic regurgitation severity, graded by a comprehensive integrated approach. Main Outcomes and Measures: The primary outcome was the association between volume-derived LVEF, LVESDi, and LVESVi and all-cause death (ACD). The secondary outcome was the association of these LV indexes with cardiovascular death (CVD). Clinical and echocardiographic data were analyzed retrospectively. A de novo disk-summation method was used to derive LV volumes and volume-derived LVEF. Results: Of 1259 patients (mean [SD] age, 64 [17] years; 934 [74%] male), 515 (41%) were Japanese and 744 (59%) were Taiwanese. The median follow-up was 4.1 years (IQR, 1.56-7.24 years). The mean (SD) body surface area was 1.67 (0.21) m2; LVEF, 55% (11%); LVESDi, 24.7 (5.7) mm/m2; LVESVi, 50.1 (28.0) mL/m2; and indexed mid-ascending aorta size, 24.7 (5.5) mm/m2. Aortic valve surgery occurred in 483 patients (38%); 240 patients (19%) died during follow-up. Overall mean (SD) 8-year survival was 74% (2%). Separate multivariate models adjusted for covariates demonstrated independent associations of LVEF, LVESDi, and LVESVi with ACD (LVEF: hazard ratio [HR] per 10%, 0.80; 95% CI, 0.70-0.92; P = .002; LVESDi: HR, 1.04; 95% CI, 1.01-1.06; P = .002; LVESVi: HR per 10 mL/m2, 1.11; 95% CI, 1.05-1.17; P < .001) and CVD (LVEF: HR per 10%, 0.69; 95% CI, 0.56-0.85; P < .001; LVESDi: HR, 1.05; 95% CI, 1.01-1.09; P = .01; LVESVi per 10 mL/m2: HR, 1.15; 95% CI, 1.06-1.24; P < .001). In the total cohort, spline curves showed that mortality started to increase for an LVEF of 53% or less, LVESDi of 22 mm/m2 or greater, and LVESVi of 46 mL/m2 or greater for both ACD and CVD. Early surgery was beneficial in 3 strata of LVESDi (<20, 20 to <25, and ≥25 mm/m2) and 2 strata of LVESVi (<46 and ≥46 mL/m2). Conclusions and Relevance: This multicenter cohort study of Asian patients with hemodynamically significant AR found cutoff values of LVEF, LVESDi, and LVESVi that were associated with increased risk of death. These findings suggest that Western guidelines seem applicable in Asian patients and, most importantly, that indexed LV parameters with a lower cutoff could be used in discriminating patients with excess mortality risk.
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Insuficiencia de la Válvula Aórtica , Humanos , Adulto , Masculino , Persona de Mediana Edad , Femenino , Insuficiencia de la Válvula Aórtica/cirugía , Volumen Sistólico , Función Ventricular Izquierda , Estudios Retrospectivos , Estudios de CohortesRESUMEN
Importance: Recent evidence indicates the efficacy of ß-amyloid immunotherapy for the treatment of Alzheimer disease, highlighting the need to promote ß-amyloid removal from the brain. Cilostazol, a selective type 3 phosphodiesterase inhibitor, promotes such clearance by facilitating intramural periarterial drainage. Objective: To determine the safety and efficacy of cilostazol in mild cognitive impairment. Design, Setting, and Participants: The COMCID trial (A Trial of Cilostazol for Prevention of Conversion from Mild Cognitive Impairment to Dementia) was an investigator-initiated, double-blind, phase 2 randomized clinical trial. Adult participants were registered between May 25, 2015, and March 31, 2018, and received placebo or cilostazol for up to 96 weeks. Participants were treated in the National Cerebral and Cardiovascular Center and 14 other regional core hospitals in Japan. Patients with mild cognitive impairment with Mini-Mental State Examination (MMSE) scores of 22 to 28 points (on a scale of 0 to 30, with lower scores indicating greater cognitive impairment) and Clinical Dementia Rating scores of 0.5 points (on a scale of 0, 0.5, 1, 2, and 3, with higher scores indicating more severe dementia) were enrolled. The data were analyzed from May 1, 2020, to December 1, 2020. Interventions: The participants were treated with placebo, 1 tablet twice daily, or cilostazol, 50 mg twice daily, for up to 96 weeks. Main Outcomes and Measures: The primary end point was the change in the total MMSE score from baseline to the final observation. Safety analyses included all adverse events. Results: The full analysis set included 159 patients (66 [41.5%] male; mean [SD] age, 75.6 [5.2] years) who received placebo or cilostazol at least once. There was no statistically significant difference between the placebo and cilostazol groups for the primary outcome. The least-squares mean (SE) changes in the MMSE scores among patients receiving placebo were -0.1 (0.3) at the 24-week visit, -0.8 (0.3) at 48 weeks, -1.2 (0.4) at 72 weeks, and -1.3 (0.4) at 96 weeks. Among those receiving cilostazol, the least-squares mean (SE) changes in MMSE scores were -0.6 (0.3) at 24 weeks, -1.0 (0.3) at 48 weeks, -1.1 (0.4) at 72 weeks, and -1.8 (0.4) at 96 weeks. Two patients (2.5%) in the placebo group and 3 patients (3.8%) in the cilostazol group withdrew owing to adverse effects. There was 1 case of subdural hematoma in the cilostazol group, which may have been related to the cilostazol treatment; the patient was successfully treated surgically. Conclusions and Relevance: In this randomized clinical trial, cilostazol was well tolerated, although it did not prevent cognitive decline. The efficacy of cilostazol should be tested in future trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02491268.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Demencia , Adulto , Humanos , Masculino , Anciano , Femenino , Cilostazol/uso terapéutico , Disfunción Cognitiva/tratamiento farmacológico , Péptidos beta-AmiloidesRESUMEN
Introduction: The insufficient quantity and quality of clinical epidemiological evidence in the field of rare diseases have posed methodological challenges to develop clinical practice guidelines (CPGs). Guideline development groups struggle to provide patients and their families with beneficial guidance, such as that for medical care and in complex circumstances. Motivated by the challenges, we focused on information on resources for supporting the daily and social life to improve the CPGs for users. We aimed to assess the methodological quality of CPGs for rare diseases in Japan and to evaluate information on resources to support the daily and social life in the CPGs. Methods: We conducted a systematic search using PubMed, three electronic Japanese databases, and two hand-searched sources in Japan. The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument with six domains was used to assess the methodological quality of the CPGs. A content analysis of the CPG text was conducted using five keywords as information on non-medical resources, e.g., "Intractable Disease Consultation Support Center," "Japan Intractable Disease Information Center," and "Patient Association." Results: A total of 55 CPGs met the inclusion criteria. Among four domains of AGREE II with low scores (Stakeholder Involvement, Rigor of Development, Applicability, and Editorial Independence), Rigor of Development had the lowest median score. As for information on non-medical resources, 41 CPGs included at least 1 of the 5 keywords, while 14 CPGs included none. Conclusions: At the Rigor of Development domain, methodological challenges may have resulted in an insufficient description of items regarding the translation evidence to recommendations. As the sufficiency of five keywords as information on non-medical resources could be improved, the information will be advocative as clues to provide pragmatic guidance, particularly for rare diseases with limited medical evidence.
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BACKGROUND: Lipid-rich plaque is an important substrate that causes future coronary events. However, the clinical implications of underlying plaque characteristics in coronary lesions after newer-generation drug-eluting stent (DES) implantation remain unknown. METHODS: The current study analyzed 445 target lesions after newer-generation DES implantation in 416 patients with coronary artery disease (CAD) (chronic coronary syndrome/acute coronary syndrome = 264/181) from the REASSURE-NIRS multicentre registry. Near-infrared spectroscopy (NIRS) imaging was used to evaluate maximum lipid core burden index after stent implantation in target lesions (residual maxLCBI4mm). The primary and secondary outcomes were 3-year lesion-oriented clinical outcomes (LOCO): cardiac death, nonfatal target-lesion-related myocardial infarction (MI), or ischemia-driven target-lesion revascularization (ID-TLR) and patient-oriented clinical outcomes (POCO): all-cause death, nonfatal MI, or ID unplanned revascularization. Outcomes were compared by residual maxLCBI4mm tertile. RESULTS: Median residual maxLCBI4mm was 183; 16% of lesions had residual maxLCBI4mm > 400. Higher residual maxLCBI4mm was not associated with a greater likelihood of LOCO or POCO during the observational period (LOCO, log-rank P = 0.76; POCO, log-rank P = 0.84). Mixed-effects logistic regression demonstrated that residual maxLCBI4mm does not predict LOCO (odds ratio [OR], 1.000; 95% confidence interval [CI], 0.997-1.003; P = 0.95). There was no significant relationship between residual maxLCBI4mm and POCO (OR, 1.001; 95% CI, 0.999-1.002; P = 0.30). CONCLUSIONS: Residual maxLCBI4mm is not associated with LOCO or POCO in patients with CAD after newer-generation DES implantation. Our findings suggest that NIRS-derived underlying lipid-rich plaque is not associated with the risk of stent-related events and patient-based outcomes in patients with CAD who have received newer-generation DESs.