Search

Abstract Background Dynapenic obesity is a condition characterized by high adiposity levels combined with muscle dysfunction. Although high adiposity and muscle loss/dysfunction are thought to synergistically increase the risk of cardiovascular disease (CVD), few studies have addressed the association between dynapenic and sarcopenic obesity and CVD. We aimed to investigate the association of dynapenic obesity with incident CVD events using the data from a population‐based prospective longitudinal study in Japan. Methods A total of 2490 community‐dwelling Japanese aged 40–79 years (42.5% males, mean age 57.7 ± 10.6 years) without a history of CVD were followed up for a median of 24 years. Handgrip strength was classified as low, medium, or high by age‐ and sex‐specific tertiles. Body mass index (BMI) levels were categorized as lean (

Abstract The genetic architecture of white matter lesions (WMLs) in Asian populations has not been well-characterized. Here, we performed a genome-wide association study (GWAS) to identify loci associated with the WML volume. Brain MRI and DNA samples were collected from 9479 participants in the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD). The GWAS confirmed three known WML-associated loci (SH3PXD2A, GFAP, and TRIM47). The lead variant of GFAP was a common missense variant (p.D295N) in East Asians. Meta-GWAS using the publicly available summary statistics of UK Biobank identified one previously unreported locus 6q23.2 (SLC2A12). Integration with expression quantitative trait locus data implied the newly identified locus affects SLC2A12 expression. The effect sizes of 20 lead variants at the WML-associated loci were moderately correlated between JPSC-AD and UK Biobank. These results indicate that the alteration in GFAP protein caused by the common missense variant in East Asians influences the WML volume.

Background: Studies on the association between preserved ratio impaired spirometry (PRISm) and dementia are limited. Indeed, PRISm has often been overlooked or ignored as an index of lung function impairment. Therefore, we investigated the association of PRISm with the risk for the development of dementia in an older Japanese population. Methods: A total of 1,202 community-dwelling, older Japanese participants aged ≥65 years without dementia were followed up for a median of 5.0 years. Participants were categorized by spirometry as follows: normal spirometry (FEV1/FVC ≥0.70 and FEV1 ≥80% predicted), PRISm (≥0.70 and

Abstract We investigated the association of retinopathy with the risk of dementia in a general older Japanese population. A total of 1709 population-based residents aged 60 years or older without dementia were followed prospectively for 10 years (2007–2017). They underwent color fundus photography in 2007. Retinopathy was graded according to the Modified Airlie House Classification. Main outcome was the Incidence of dementia. A Cox proportional hazards model was used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) for the risk of dementia by the presence of retinopathy. During the follow-up period, 374 participants developed all-cause dementia. The cumulative incidence of dementia was significantly higher in those with retinopathy than those without (p

Abstract In recent years, the association between neuroinflammatory markers and dementia, especially Alzheimer’s disease (AD), has attracted much attention. However, the evidence for the relationship between serum-hs-CRP and dementia including AD are inconsistent. Therefore, the relationships of serum high-sensitivity CRP (hs-CRP) with dementia including AD and with regions of interest of brain MRI were investigated. A total of 11,957 community residents aged 65 years or older were recruited in eight sites in Japan (JPSC-AD Study). After applying exclusion criteria, 10,085 participants who underwent blood tests and health-related examinations were analyzed. Then, serum hs-CRP levels were classified according to clinical cutoff values, and odds ratios for the presence of all-cause dementia and its subtypes were calculated for each serum hs-CRP level. In addition, the association between serum hs-CRP and brain volume regions of interest was also examined using analysis of covariance with data from 8614 individuals in the same cohort who underwent brain MRI. After multivariable adjustment, the odds ratios (ORs) for all-cause dementia were 1.04 (95% confidence interval [CI] 0.76–1.43), 1.68 (95%CI 1.08–2.61), and 1.51 (95%CI 1.08–2.11) for 1.0–1.9 mg/L, 2.0–2.9 mg/L, and ≥ 3.0 mg/L, respectively, compared to

Background: The association between chronic lipopolysaccharide exposure and the development of metabolic syndrome (MetS) is unclear. In this study we examined the association between serum lipopolysaccharide-binding protein (LBP) levels, an indicator of lipopolysaccharide exposure, and the development of MetS in a general Japanese population. Methods: 1,869 community-dwelling Japanese individuals aged ≥40 years without MetS at baseline examination in 2002–2003 were followed up by repeated examination in 2007–2008. MetS was defined according to the Japanese criteria. Serum LBP levels were classified into quartiles (quartiles 1–4: 2.20–9.56, 9.57–10.78, 10.79–12.18, and 12.19–24.34 µg/mL, respectively). Odds ratios (ORs) for developing MetS were calculated using a logistic regression model. Results: At the follow-up survey, 159 participants had developed MetS. Higher serum LBP levels were associated with greater risk of developing MetS after multivariable adjustment for age, sex, smoking, drinking, and exercise habits (OR [95% confidence interval] for quartiles 1–4: 1.00 [reference], 2.92 [1.59–5.37], 3.48 [1.91–6.35], and 3.86 [2.12–7.03], respectively; P for trend

Introduction Data on the prevalence of muscle-strengthening activities in Asia have been limited. Using data from a community-based cross-sectional survey of a general adult population in Japan, whose age and occupational distribution were very similar to the national averages, we aimed to estimate the prevalence of muscle-strengthening activities.Methods A community survey of local residents over 40 years of age was conducted in 2017–2018 as part of the Hisayama Study. Information on muscle-strengthening activities was obtained by means of a face-to-face interview by nurses. The prevalence of muscle-strengthening activities according to sex and age groups was estimated using a modified Poisson regression model. The prevalence ratios by subgroups based on anthropometry, physical conditions and lifestyle and behavioural factors were also estimated.Results Data on muscle-strengthening activities were available on 1509 men and 1946 women. Overall, 162 individuals (4.7%) engaged in muscle-strengthening activities at least 1 day/week, and 133 (3.8%) did so for 2 days or more per week. Women were less likely to engage in muscle-strengthening activities than men. The prevalence was generally comparable across subgroups of covariates, while an even lower prevalence was observed for some specific subpopulations, including individuals with diabetes and current smokers.Conclusions The prevalence of muscle-strengthening activities was estimated to be low in a general Japanese adult population. Population-wide approaches for the entire country and tailored educational interventions for specific subpopulations may be necessary in order to effectively enhance the participation in muscle-strengthening activities at a population level.

Purpose: To examine the association between choroidal thickness and myopic maculopathy in a general Japanese population. Design: Population-based cross-sectional study. Participants: A total of 2841 residents of a Japanese community aged ≥ 40 years, who consented to participate and had available data of choroidal thickness and fundus photographs, were enrolled in this study. Methods: The choroidal thickness was measured by swept-source OCT. Participants were divided into quartiles of choroidal thickness. Myopic maculopathy was defined according to the classification system of the Meta-analysis of Pathologic Myopia Study Group. Main outcome measures were odds ratios (ORs) of choroidal thickness for prevalent myopic maculopathy. The ORs and 95% confidence intervals (CIs) were estimated using a logistic regression model. Main Outcome Measures: Prevalent myopic maculopathy. Results: Eighty-one participants had myopic maculopathy (45 diffuse chorioretinal atrophy, 31 patchy chorioretinal atrophy, and 5 macular atrophy). Individuals in the lowest quartile of choroidal thickness had a significantly greater OR for the presence of myopic maculopathy than those in the highest quartile of choroidal thickness (OR: 4.78 [95% CI: 1.78–16.72]) after adjusting for confounders, including axial length. The sensitivity analysis among the 1176 myopic individuals with axial length of ≥ 24.0 mm also showed that thinner choroidal thickness was significantly associated with prevalent myopic maculopathy. Conclusions: The present study demonstrated the significant inverse association between choroidal thickness and the likelihood of myopic maculopathy, suggesting that the measurement of choroidal thickness in addition to axial length would be useful for assessing the risk of myopic maculopathy and elucidating its pathogenesis. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Abstract Aims/Introduction We aimed to investigate the association of active commuting (cycling or walking to work), as well as the association of the individual commuting modes, with the risk of diabetes in a prospective cohort of community‐dwelling adults in Japan. Material and Methods A total of 1,270 residents aged 40–79 years were followed up for a median of 14 years. Active commuting was defined as either cycling or walking to work. A Cox proportional hazards model was used to examine the association of active commuting with the risk of diabetes. Associations for different forms of active commuting (cycling, walking and mixed modes of cycling or walking with non‐active components) were also examined. Results During the follow‐up period, 191 participants developed diabetes. Active commuting was associated with a lower risk of diabetes than non‐active commuting after adjustment for potential confounders (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.31–0.92). With regard to the commuting modes, the risk of diabetes was significantly lower in individuals who commuted by cycling alone (HR 0.46, 95% CI 0.22–0.98), and tended to be lower in individuals who commuted by walking alone (HR 0.14, 95% CI 0.02–1.02) compared with that in individuals with non‐active commuting. Meanwhile, no significant associations were observed for the mixed mode of walking and non‐active commuting (HR 1.69, 95% CI 0.77–3.71). Conclusions Active commuting, particularly that consisting exclusively of cycling or walking, was associated with a reduced risk of diabetes. Our findings support a public health policy that promotes the choice of active commuting for the prevention of diabetes.

Abstract Physical frailty has been associated with adverse outcomes such as dementia. However, the underlying structural brain abnormalities of physical frailty are unclear. We investigated the relationship between physical frailty and structural brain abnormalities in 670 cognitively unimpaired individuals (mean age 70.1 years). Total brain volume (TBV), hippocampal volume (HV), total white matter hypointensities volume (WMHV), and estimated total intracranial volume (eTIV) on the 3D T1-weighted images were automatically computed using FreeSurfer software. Participants were divided into two states of physical frailty (robust vs. prefrail) based on the revised Japanese version of the Cardiovascular Health Study criteria. The multivariable-adjusted mean values of the TBV-to-eTIV ratio was significantly decreased, whereas that of the WMHV-to-eTIV ratio was significantly increased in the prefrail group compared with the robust group. Slowness, one of the components of physical frailty, was significantly associated with reduced TBV-to-eTIV and HV-to-eTIV ratios, and slowness and weakness were significantly associated with an increased WMHV-to-eTIV ratio. Our results suggest that the prefrail state is significantly associated with global brain atrophy and white matter hypointensities. Furthermore, slowness was significantly associated with hippocampal atrophy.

Abstract We examined the association of serum s-adenosylmethionine (SAM), s-adenosylhomocysteine (SAH) (methionine metabolites), and their ratio on the risk of dementia and death in a community-dwelling population of older Japanese individuals. 1371 residents of Hisayama, Japan, aged 65 years or older and without dementia, were followed for a median of 10.2 years (2007–2017). We divided serum SAM, SAH, and SAM/SAH ratio into quartiles. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) of serum SAM, SAH, and SAM/SAH ratio levels on the risk of a composite outcome of all-cause dementia or death, and each outcome. During the follow-up, 635 participants developed all-cause dementia and/or died, of which 379 participants developed dementia and 394 deaths occurred. The multivariable-adjusted HRs of the composite outcome decreased significantly with increasing serum SAM levels (P for trend = 0.01), while they increased significantly with higher serum SAH levels (P for trend = 0.03). Higher serum SAM/SAH ratio levels were significantly associated with a lower risk of the composite outcome (P for trend = 0.002), as well as with lower risk of each outcome. Our findings suggest that the balance of methionine metabolites may closely associate with the risk of dementia and death.

Abstract Background Several prospective Western studies have reported an inverse association of vegetable and fruit intake with dementia risk. However, there is limited epidemiologic evidence in Asians. This study investigated the association of intakes of vegetables, fruits, and their nutrients on the risk of incident dementia and its subtypes in a Japanese community. Methods A total of 1071 participants (452 men and 619 women) aged ≥60 years without dementia at baseline were prospectively followed up for 24 years. Intakes of vegetables, fruits, and nutrients were evaluated using a 70-item semiquantitative food frequency questionnaire at baseline and were categorized into quartiles separately by gender. The outcome measure was the development of dementia and its subtypes—namely, Alzheimer’s disease (AD) and vascular dementia (VaD). The risk estimates of incident dementia were computed using a Cox proportional hazards model. Results During the long-term follow-up period, 464 subjects developed dementia, of whom 286 had AD and 144 had VaD. Higher vegetable intake was associated gradually with lower risk of developing dementia and AD (both P-trend

Rationale & Objective: Chronic kidney disease, defined by albuminuria and/or reduced estimated glomerular filtration rate (eGFR), has been reported to be associated with brain atrophy and/or higher white matter lesion volume (WMLV), but there are few large-scale population-based studies assessing this issue. This study aimed to examine the associations between the urinary albumin-creatinine ratio (UACR) and eGFR levels and brain atrophy and WMLV in a large-scale community-dwelling older population of Japanese. Study Design: Population-based cross-sectional study. Setting & Participants: A total of 8,630 dementia-free community-dwelling Japanese aged greater than or equal to 65 years underwent brain magnetic resonance imaging scanning and screening examination of health status in 2016-2018. Exposures: UACR and eGFR levels. Outcomes: The total brain volume (TBV)-to-intracranial volume (ICV) ratio (TBV/ICV), the regional brain volume-to-TBV ratio, and the WMLV-to-ICV ratio (WMLV/ICV). Analytical Approach: The associations of UACR and eGFR levels with the TBV/ICV, the regional brain volume-to-TBV ratio, and the WMLV/ICV were assessed by using an analysis of covariance. Results: Higher UACR levels were significantly associated with lower TBV/ICV and higher geometric mean values of the WMLV/ICV (P for trend = 0.009 and

Abstract Aims/Introduction To investigate the association between midlife or late‐life diabetes and the development of sarcopenia in an older Japanese population. Materials and Methods A total of 824 Japanese residents aged 65 to 84 years without sarcopenia were followed up from 2012 to 2017. Sarcopenia was determined following the Asian Working Group for Sarcopenia definition. The time of diabetes diagnosis was classified as midlife or late‐life diabetes by the age at first diagnosis of diabetes (< 65 or ≥ 65 years) based on annual health checkups data over the past 24 years. The duration of diabetes was categorized into three groups of 15 years. The odds ratios of incident sarcopenia according to the diabetic status were estimated using a logistic regression analysis. Results During follow‐up, 47 subjects developed sarcopenia. The multivariable‐adjusted odds ratio for incident sarcopenia was significantly greater in subjects with diabetes at baseline than in those without it (odds ratio 2.51, 95% confidence interval 1.26–5.00). Subjects with midlife diabetes had a significantly greater risk of incident sarcopenia, whereas no significant association between late‐life diabetes and incident sarcopenia was observed. With a longer duration of diabetes, the risk of incident sarcopenia increased significantly (P for trend = 0.002). Conclusions The present study suggests that midlife diabetes and a longer duration of diabetes are significant risk factors for incident sarcopenia in the older population. Preventing diabetes in midlife may reduce the risk of the development of sarcopenia in later life.

Background Several longitudinal studies have reported that higher visit‐to‐visit blood pressure variability is associated with greater risk for developing chronic kidney disease. However, no population‐based studies have investigated the association between day‐to‐day home blood pressure variability and incident chronic kidney disease. Methods and Results A total of 2342 Japanese community‐dwelling residents aged ≥40 years without chronic kidney disease at baseline were followed up by annual health examinations for 10 years. Home blood pressure was measured 3 times every morning for 28 days. Day‐to‐day coefficients of variation of home systolic blood pressure levels were categorized into quintiles. Chronic kidney disease was defined as an estimated glomerular filtration rate

Background: The prevalence of sarcopenia defined using the Asian Working Group for Sarcopenia (AWGS) criteria in Asian communities has not been fully addressed. Moreover, few studies have addressed the influence of sarcopenia on mortality. Methods: A total of 1,371 and 1,597 residents aged 65 years or older participated in health surveys in 2012 and 2017. Sarcopenia was determined using the AWGS definition. Factors associated with the presence of sarcopenia were assessed using a logistic regression model in participants in the 2012 survey. Subjects in the 2012 survey were followed-up prospectively for a median of 4.3 years. Mortality risk for subjects with sarcopenia was examined using the Cox proportional hazards model. Results: The crude prevalence of sarcopenia was 7.4% and 6.6% in participants at the 2012 and 2017 surveys, respectively; there was no significant difference between surveys (P = 0.44). The prevalence of sarcopenia increased significantly with age in both sexes (both P for trend

Introduction: Serum N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels have been associated with the progression of kidney impairment among patients with chronic kidney disease (CKD), but only a few studies have investigated the association between serum NT-proBNP levels and incident CKD in general populations. Methods: A total of 2486 Japanese community-dwelling residents ≥40 years of age without CKD at baseline were followed up by repeated annual health examinations for 10 years. Participants were divided into 4 groups according to serum NT-proBNP levels. CKD was defined as an estimated glomerular filtration rate (eGFR)

Abstract Background Epidemiological evidence has shown that serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations, a diagnostic biomarker for heart failure, are positively associated with cardiovascular risk. Since NT-proBNP in serum is excreted in urine, it is hypothesized that urinary NT-proBNP concentrations are correlated with serum concentrations and linked with cardiovascular risk in the general population. Methods A total of 3060 community-dwelling residents aged ≥ 40 years without history of cardiovascular disease (CVD) were followed up for a median of 8.3 years (2007–2015). Serum and urinary concentrations of NT-proBNP at baseline were compared. The hazard ratios (HRs) and their 95% confidence intervals (CIs) for the association between NT-proBNP concentrations and the risk of developing CVD were computed using the Cox proportional hazards model. Results The median values (interquartile ranges) of serum and urinary NT-proBNP concentrations at baseline were 56 (32–104) pg/mL and 20 (18–25) pg/mL, respectively. There was a strong quadratic correlation between the serum and urinary concentrations of NT-proBNP (coefficient of determination [R 2] = 0.72): urinary concentrations of 20, 27, and 43 pg/mL were equivalent to serum concentrations of 55, 125, and 300 pg/mL, respectively. During the follow-up period, 170 subjects developed CVD. The age- and sex-adjusted risk of CVD increased significantly with higher urinary NT-proBNP levels (P for trend < 0.001). This association remained significant after adjustment for traditional cardiovascular risk factors (P for trend = 0.009). The multivariable-adjusted risk of developing CVD almost doubled in subjects with urinary NT-proBNP of ≥ 43 pg/mL as compared to those with urinary NT-proBNP of ≤ 19 pg/mL (HR 2.07, 95% CI 1.20–3.56). Conclusions The present study demonstrated that urinary NT-proBNP concentrations were well-correlated with serum concentrations and were positively associated with cardiovascular risk. Given that urine sampling is noninvasive and does not require specially trained personnel, urinary NT-proBNP concentrations have the potential to be an easy and useful biomarker for detecting people at higher cardiovascular risk.

Abstract Aims/Introduction The investigation of the influence of dietary fiber intake on the incidence of type 2 diabetes in a general Japanese population. Materials and Methods A total of 1,892 individuals aged 40–79 years without diabetes at baseline were prospectively followed up for 14 years. The glucose tolerance status of participants was defined by a 75‐g oral glucose tolerance test with the 1998 World Health Organization criteria. Dietary fiber intake was estimated by a semiquantitative food frequency questionnaire and divided to quintile levels separately by sex. A Cox proportional hazards model was applied for computing the hazard ratios and their 95% confidence intervals for the incidence of diabetes. Results During the follow‐up period, 280 participants had developed diabetes. The age‐adjusted cumulative diabetes incidence decreased significantly with higher total dietary fiber intake (P‐for trend = 0.01). Participants in the highest quintile of total dietary fiber intake had a 0.53‐fold (95% confidence interval 0.31–0.90) lower risk of developing diabetes than those in the lowest quintile after for the adjustment with potential confounding factors. Total dietary fiber intake showed a moderate positive correlation to the intake of soybean and soybean products, green vegetables, and other vegetables. Similar associations with diabetes and food sources were observed for both of the soluble and insoluble dietary fiber intake. Conclusions The present study showed that higher dietary fiber intake was associated with a lower risk of type 2 diabetes in a general Japanese population. The intake of high dietary fiber foods might be useful for diabetes prevention.

Purpose: To assess the association of inner retinal thickness with prevalent dementia and regional brain atrophy in a general older population of Japanese. Design: Population-based, cross-sectional study. Participants: A total of 1078 residents aged 65 years or older who participated in an eye examination, a comprehensive survey of dementia, and brain magnetic resonance imaging scanning in 2017. Methods: The thicknesses of the inner retinal layers, namely, the ganglion cell-inner plexiform layer (GC-IPL) and retinal nerve fiber layer (RNFL)—were measured by swept-source OCT (SS-OCT). The association of these retinal thicknesses with the risk of the presence of dementia was estimated using restricted cubic splines and logistic regression models. Regional brain volumes were estimated separately by applying 2 different methods: voxel-based morphometry (VBM) and analysis by FreeSurfer software. The associations of GC-IPL and RNFL thickness with each brain regional volume were analyzed using multiple regression analysis. Main Outcome Measure: Prevalent dementia and regional brain atrophy. Results: Among the study participants, 61 participants (5.7%) were diagnosed with dementia. The likelihood of the presence of dementia significantly increased with lower GC-IPL thickness after adjusting for potential confounders (odds ratio, 1.62 [95% confidence interval, 1.30–2.01] per 1 standard deviation decrement in the GC-IPL thickness), but no significant association was observed with RNFL thickness. In the VBM analyses with the multivariable adjustment, lower GC-IPL thickness was significantly associated with lower volume of known brain regions related to cognitive functions (i.e., the hippocampus, amygdala, entorhinal area, and parahippocampal gyrus) and visual functions (i.e., the cuneus, lingual gyrus, and thalamus). Meanwhile, the volume of the thalamus significantly decreased with lower RNFL thickness, but none of the brain regions related to cognitive function exhibited a volume change in association with RNFL thickness. The sensitivity analysis using FreeSurfer analysis also showed that lower GC-IPL thickness was significantly associated with lower regional brain volume/intracranial volume of the hippocampus, amygdala, cuneus, lingual gyrus, and thalamus. Conclusions: Our findings suggest that the measurement of GC-IPL thickness by SS-OCT, which is a noninvasive, convenient, and reproducible method, might be useful for identifying high-risk individuals with dementia.

Abstract Background The burden of dementia is growing rapidly and has become a medical and social problem in Japan. Prospective cohort studies have been considered an effective methodology to clarify the risk factors and the etiology of dementia. We aimed to perform a large-scale dementia cohort study to elucidate environmental and genetic risk factors for dementia, as well as their interaction. Methods The Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) is a multisite, population-based prospective cohort study of dementia, which was designed to enroll approximately 10,000 community-dwelling residents aged 65 years or older from 8 sites in Japan and to follow them up prospectively for at least 5 years. Baseline exposure data, including lifestyles, medical information, diets, physical activities, blood pressure, cognitive function, blood test, brain magnetic resonance imaging (MRI), and DNA samples, were collected with a pre-specified protocol and standardized measurement methods. The primary outcome was the development of dementia and its subtypes. The diagnosis of dementia was adjudicated by an endpoint adjudication committee using standard criteria and clinical information according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd Revised Edition. For brain MRI, three-dimensional acquisition of T1-weighted images was performed. Individual participant data were pooled for data analyses. Results The baseline survey was conducted from 2016 to 2018. The follow-up surveys are ongoing. A total of 11,410 individuals aged 65 years or older participated in the study. The mean age was 74.4 years, and 41.9% were male. The prevalence of dementia at baseline was 8.5% in overall participants. However, it was 16.4% among three sites where additional home visit and/or nursing home visit surveys were performed. Approximately two-thirds of dementia cases at baseline were Alzheimer’s disease. Conclusions The prospective cohort data from the JPSC-AD will provide valuable insights regarding the risk factors and etiology of dementia as well as for the development of predictive models and diagnostic markers for the future onset of dementia. The findings of this study will improve our understanding of dementia and provide helpful information to establish effective preventive strategies for dementia in Japan.

Abstract Aims/Introduction Changes in histologically quantified β‐ and α‐cell mass during the development of glucose intolerance have not been fully elucidated. The aim of the present study was to explore differences in β‐ and α‐cell mass according to the glucose tolerance status. Materials and Methods Autopsy samples from a total of 103 individuals (40 with normal glucose tolerance, 31 with prediabetes and 32 with type 2 diabetes mellitus) who underwent a 75‐g oral glucose tolerance test within 5 years before death were selected from 643 community‐based autopsy samples collected from 2002 to 2016. Fractional β‐cell area (BCA) and α‐cell area were quantified with Image Pro Plus software. Associations of BCA and α‐cell area with glucose tolerance status were assessed using a linear regression analysis, and Spearman’s correlation coefficients between glycemic markers and β‐cell function were estimated. Results The mean values of BCA decreased significantly with worsening glucose tolerance status (mean ± standard error 1.85 ± 0.10% in normal glucose tolerance, 1.59 ± 0.11% in prediabetes and 1.17 ± 0.11% in type 2 diabetes mellitus, P for trend

Abstract Aims/Introduction To investigate the association of alternative glycemic measures – namely, serum glycated albumin (GA), hemoglobin A1c (HbA1c) and the GA : HbA1c ratio – with global brain and hippocampal atrophy in a general elderly Japanese population. Materials and Methods A total of 1,278 Japanese individuals aged ≥65 years in a community participated in brain magnetic resonance imaging scanning and screening examination of health status in 2012. We measured total brain volume (TBV), hippocampal volume (HV) and intracranial volume (ICV) using the data from the magnetic resonance imaging examination. The association of each glycemic measure with the ratios of TBV : ICV (an indicator of global brain atrophy) and HV : ICV (an indicator of hippocampal atrophy) was examined by analysis of covariance. Results The mean values of the TBV : ICV and HV : ICV ratios decreased significantly with elevating serum GA levels and GA : HbA1c ratio levels (all P for trend

Abstract Aims/Introduction Resistin is an adipocyte‐derived polypeptide that leads to the progression of insulin resistance and subsequent atherosclerosis. Some studies have reported an association between self‐reported intake of n−3 polyunsaturated fatty acids (PUFAs) and serum resistin levels. However, no studies have investigated the association between the ratio of serum levels of n−3 to serum n−6 PUFAs and the serum resistin concentration in the general population. Materials and Methods We carried out a cross‐sectional study of 3,200 community‐dwelling Japanese individuals aged ≥40 years in 2002–2003. The ratios of serum eicosapentaenoic acid or docosahexaenoic acid to arachidonic acid (AA) were categorized into quartiles. The associations of serum eicosapentaenoic acid/AA and docosahexaenoic acid/AA with the serum resistin concentration were assessed using linear regression models with adjustment for potential confounding factors. Results The geometric mean of serum resistin was 10.3 ng/mL. The age‐ and sex‐adjusted geometric mean of serum resistin decreased significantly with increased levels of serum eicosapentaenoic acid/AA (quartile 1: 11.3 ng/mL; quartile 2: 10.6 ng/mL; quartile 3: 10.3 ng/mL; quartile 4: 9.3 ng/mL; P for trend

Background: The association between decline in handgrip strength from midlife to late life and dementia is unclear. Methods: Japanese community-dwellers without dementia aged 60 to 79 years (ie, individuals in late life; mean age, 68 years) were followed for 24 years (1988–2012) (n = 1,055); 835 of them had participated in a health examination in 1973–1974 (mean age, 53 years), and these earlier data were used for the midlife analysis. Using a Cox proportional hazards model, we estimated the risk conferred by a decline in handgrip strength over a 15-year period (1973–74 to 1988) from midlife to late life on the development of total dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) over the late-life follow-up period from 1988 to 2012. Results: During the follow-up, 368 subjects experienced total dementia. The age- and sex-adjusted incidence of total dementia increased significantly with greater decline in handgrip strength (increased or unchanged handgrip strength [≥+0%] 25.1, mildly decreased [−14 to −1%] 28.4, and severely decreased [≤−15%] 38.9 per 1,000 person-years). A greater decline in handgrip strength was significantly associated with higher risk of total dementia after adjusting for potential confounding factors; subjects with severely decreased handgrip strength had 1.51-fold (95% confidence interval, 1.14–1.99, P < 0.01) increased risk of total dementia compared to those with increased or unchanged handgrip strength. Similar significant findings were observed for AD, but not for VaD. Conclusions: Our findings suggest that a greater decline in handgrip strength from midlife to late life is an important indicator for late-life onset of dementia.

Objectives We examined the trend in the number of missing teeth in a Japanese community over a 10-year period and the potential associated explanatory factors.Design Prospective cohort study.Setting A population-based study conducted in 2007, 2012 and 2017 in Japan (Hisayama Study).Participants Residents of a Japanese community aged 40–79 years undergoing dental examination in 2007 (n=2665), 2012 (n=2325) and 2017 (n=2285).Outcome measures The number of missing teeth, periodontal condition, dental caries experience, dental plaque index and oral health behaviours were evaluated each year. The longitudinal analysis of variation in these factors were assessed using mixed models.Results The age-adjusted and sex-adjusted mean number of missing teeth decreased with time (6.80 in 2007, 6.01 in 2012 and 4.99 in 2017). The mean clinical attachment level (CAL), prevalence of periodontitis and dental plaque index decreased over the study period, while dental caries experience slightly increased. The level of oral health behaviour increased over time. Poisson mixed models showed that changes in mean CAL and dental caries experience were positively associated with the change in the number of missing teeth over time. Linear mixed models showed that changes in dental plaque index and no regular dental visit were positively associated with changes in mean CAL.Conclusions These findings suggest that a decreasing trend regarding the number of missing teeth in Japan might be associated with improvements in the periodontal condition due to changes in oral hygiene level and oral health behaviour.

Abstract Aims/Introduction The present study aimed to examine cross‐sectional associations between objectively measured sedentary time and the prevalence of diabetes mellitus in a general Japanese population, and to elucidate possible mediating roles of diet, obesity and insulin resistance in this relationship. Materials and Methods A total of 1,758 community‐dwelling individuals aged 40–79 years wore an accelerometer for ≥7 days and underwent a comprehensive health examination in 2012. Diabetes mellitus was diagnosed by a 75‐g oral glucose tolerance test. The associations of sedentary time with the presence of diabetes mellitus and the levels of the homeostasis model assessment of insulin resistance were estimated by logistic and linear regression models. Results After adjustment for demographic and lifestyle factors including moderate‐to‐vigorous physical activity, participants who spent ≥10 h in sedentary time had a significantly higher odds ratio of the presence of diabetes than those who spent

Background: Few risk models are available to predict future onset of atrial fibrillation (AF) in workers. We aimed to develop risk prediction models for new-onset AF, using annual health checkup (HC) data with electrocardiogram findings. Methods and Results: We retrospectively included 56,288 factory or office workers (mean age = 51.5 years, 33.0% women) who underwent a HC at a medical center and fulfilled the following criteria; age ≥ 40 years, no history of AF, and greater than 1 annual follow-up HC in 2013–2016. Using Cox models with the Akaike information criterion, we developed and compared prediction models for new-onset AF with and without the Minnesota code information. We externally validated the discrimination accuracy of the models in a general Japanese population cohort, the Hisayama cohort. During the median 3.0-year follow-up, 209 (0.37%) workers developed AF. Age, sex, waist circumference, blood pressure, LDL cholesterol, and γ-GTP were associated with new-onset of AF. Using the Minnesota code information, the AUC significantly improved from 0.82 to 0.84 in the derivation cohort and numerically improved from 0.78 to 0.79 in the validation cohort, and from 0.77 to 0.79 in the Hisayama cohort. The NRI and IDI significantly improved in all and male subjects in both the derivation and validation cohorts, and in female subjects in both the validation and the Hisayama cohorts. Conclusions: We developed useful risk model with Minnesota code information for predicting new-onset AF from large worker population validated in the original and external cohorts, although study interpretation is limited by small improvement of AUC.

Numerous oral indigenous microorganisms are constantly introduced into the stomach via the laryngopharynx, and a portion of these microorganisms irregularly reaches the lower airways and lungs. This study investigated the association between airflow limitation and the status of tongue microbiota, which is a primary source of ingested oral bacterial populations. The study population consisted of 484 community-dwelling adults aged 70–80 years inhabiting Hisayama town, Japan, who underwent a regular health examination including dental examination and spirometry test in 2016. The bacterial density and composition of their tongue microbiota were determined using a previously used 16S rRNA gene to understand their relationship with oral health conditions. The present cross-sectional study compared the tongue microbiota status between elderly individuals with airflow limitation and those with normal airflow. The total bacterial density of the tongue microbiota of individuals with airflow limitation was significantly higher than that of individuals with normal airflow. Logistic regression analysis demonstrated that a high-biomass tongue microbiota was significantly associated with airflow limitation after adjustment for smoking intensity and other covariates (adjusted OR 1.61, 95% CI 1.01–2.60). Of the predominant commensals, higher amounts of Prevotella melaninogenica and Actinomyces odontolyticus were associated with a higher prevalence of airflow limitation. These results indicate that increased bacterial burden in the tongue microbiota is associated with a higher prevalence of airflow limitation.

Abstract Introduction We aimed to develop a risk prediction model for incident dementia using predictors that are available in primary‐care settings. Methods A total of 795 subjects aged 65 years or over were prospectively followed‐up from 1988 to 2012. A Cox proportional‐hazards regression was used to develop a multivariable prediction model. The developed model was translated into a simplified scoring system based on the beta‐coefficient. The discrimination of the model was assessed by Harrell's C statistic, and the calibration was assessed by a calibration plot. Results During the follow‐up period, 364 subjects developed dementia. In the multivariable model, age, female sex, low education, leanness, hypertension, diabetes, history of stroke, current smoking, and sedentariness were selected as predictors. The developed model and simplified score showed good discrimination and calibration. Discussion The developed risk prediction model is feasible and practically useful in primary‐care settings to identify individuals at high risk for future dementia.

Disruption of the intestinal microbiota caused by intensive chemotherapy, irradiation and antibiotics can result in development of severe gut graft-versus-host disease and infectious complications, leading to poorer outcomes among allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Although the oral cavity is also densely colonized by indigenous microorganisms, the bacterial composition in allo-HSCT recipients remains unclear. We determined the tongue microbiota composition of 45 patients with hematological disorders on the day of transplantation and compared them to 164 community-dwelling adults. The V1-V2 regions of the 16S rRNA gene sequences demonstrated that the allo-HSCT recipients had less diverse and distinct microbiota from that of community-dwelling adults. The full-length 16S rRNA gene sequences identified 146 bacterial taxa in the microbiota of allo-HSCT recipients, of which 34 bacterial taxa did not correspond to bacteria primarily inhabiting the oral cavity deposited in the expanded Human Oral Microbiome Database. Notably, the detection of Staphylococcus haemolyticus and/or Ralstonia pickettii was significantly associated with a higher risk of mortality during the follow-up period. These results demonstrate that the oral cavity of allo-HSCT recipients is colonized by a disrupted microbiota on the day of transplantation and suggest that detection of specific nonindigenous taxa could be a predictor of transplant outcome.

Background: The purpose of this cross-sectional study was to describe the patterns and levels of sedentary time and physical activity (PA) in a general Japanese population. Methods: A total of 1,740 community-dwelling Japanese adults aged ≥40 years participated in this study. Sedentary time and PA were assessed for 7 consecutive days using a tri-axial accelerometer. Daily patterns and levels of sedentary time and PA were calculated by sex, age group (40–64, 65–74, and ≥75 years), and body mass index (BMI;

Background Epidemiological studies have reported a link between serum LBP (lipopolysaccharide‐binding protein) levels and lifestyle‐related diseases. However, there have been no longitudinal studies investigating the association of serum LBP levels and the incidence of cardiovascular disease (CVD) in general populations. Methods and Results A total of 2568 community‐dwelling Japanese individuals 40 years and older without prior CVD were followed for 10 years (2002–2012). Serum LBP levels were divided into quartiles (quartile 1: 2.20–9.68 μg/mL; quartile 2: 9.69–10.93 μg/mL; quartile 3: 10.94–12.40 μg/mL; quartile 4: 12.41–24.34 μg/mL). The hazard ratios (HRs) and their 95% CIs for the incidence of CVD were computed using a Cox proportional hazards model. During the follow‐up period, 180 individuals developed CVD. The age‐ and sex‐adjusted cumulative incidence of CVD increased significantly with higher serum LBP levels (P for trend=0.005). Individuals with higher serum LBP levels had a significantly greater risk of the development of CVD after adjusting for conventional cardiovascular risk factors (quartile 1: HR, 1.00 [reference]; quartile 2: HR, 1.04 [95% CI, 0.60–1.78]; quartile 3: HR, 1.52 [95% CI, 0.92–2.51]; and quartile 4: HR, 1.90 [95% CI, 1.17–3.09]; P for trend=0.01). This association remained significant after additional adjustment for homeostasis model assessment of insulin resistance (P for trend=0.01). However, when additional adjustment was made for high‐sensitivity C‐reactive protein, the association was attenuated to the nonsignificant level (P for trend=0.08). Conclusions The present findings suggest that higher serum LBP levels are associated with increased risk of the development of CVD in the general Japanese population. Low‐grade endotoxemia may contribute to the pathogenesis of CVD through chronic systemic inflammation.

Background Epidemiological evidence implies a link between heart disease and dementia. However, few prospective studies have assessed the association between serum NT‐proBNP (N‐terminal pro–B‐type natriuretic peptide) levels and dementia. Methods and Results A total of 1635 community‐dwelling Japanese elderly aged ≥60 years without dementia (57% women, mean age±SD 70.8±7.7 years) were followed up for 10 years. Serum NT‐proBNP levels were divided into 4 categories (≤54, 55‐124, 125‐299, and ≥300 pg/mL). The hazard ratios were estimated using a Cox proportional hazards model. During the follow‐up period, 377 subjects developed all‐cause dementia, 247 Alzheimer disease, and 102 vascular dementia. The age‐ and sex‐adjusted incidence of all‐cause dementia was 31.5 per 1000 person‐years and increased significantly with higher serum NT‐proBNP levels, being 16.4, 32.0, 35.7, and 45.5, respectively (P for trend

ABSTRACT Tongue microbiota are a dominant source of oral microbial populations that are ingested with saliva, and therefore careful attention is required for the maintenance of health of elderly adults, who are susceptible to aspiration of oral contents. This study aimed to investigate the variation in tongue microbiota among community-dwelling elderly adults. Following a dental examination, tongue coating was collected from a 15-mm-diameter circular area at the center of the tongue dorsum of 506 elderly adults aged 70 to 80 years inhabiting the town of Hisayama, Japan. The microbial composition and density were determined by a 16S rRNA gene sequencing approach using a next-generation sequencer and quantitative PCR analysis, respectively. Co-occurrence network analysis identified two cohabiting groups of predominant commensals, one of which was primarily composed of Prevotella histicola, Veillonella atypica, Streptococcus salivarius, and Streptococcus parasanguinis; these organisms have been previously associated with an increased risk of mortality due to pneumonia in the frail elderly. This bacterial group was more predominant in the elderly with fewer teeth, a higher plaque index, and more dental caries experience, whereas the total bacterial density was independent of these traits. A higher density of fungi was also observed in the elderly with these traits, as well as in individuals who wore dentures. These results suggest that elderly adults with poorer oral health swallow a more dysbiotic microbiota formed on the tongue. IMPORTANCE Aspiration of oral contents can lead to pneumonia, which is a major cause of death among elderly adults susceptible to swallowing impairments. Tongue microbiota are a dominant source of oral microbial populations that are ingested with saliva. This large-scale population-based study revealed variations in the tongue microbiota among community-dwelling elderly adults. The total bacterial density was independent of the conditions of teeth surrounding the tongue, whereas the microbiota composition, especially the relative abundances of predominant commensals, showed an association with tooth conditions. Our results demonstrate that the elderly with fewer teeth, poorer dental hygiene, and more dental caries experience constantly ingest more dysbiotic microbiota, which could be harmful for their respiratory health.

BackgroundEpidemiologic evidence has emerged to reveal an association of albuminuria and low estimated glomerular filtration rate (eGFR) with dementia, but the findings are inconsistent. In addition, there are limited studies addressing the association between albuminuria and Alzheimer disease (AD). Methods and ResultsA total of 1562 community‐dwelling Japanese subjects aged ≥60 years without dementia were followed up for 10 years. The outcomes were incidence of all‐cause dementia and its subtypes, namely, AD and vascular dementia (VaD). The hazard ratios for the outcomes were estimated according to urine albumin–creatinine ratio (UACR) and eGFR levels using a Cox proportional hazards model. During the follow‐up, 358 subjects developed all‐cause dementia (238 AD and 93 VaD). Higher UACR level was significantly associated with greater multivariable‐adjusted risks of all‐cause dementia (hazard ratios [95% confidence intervals]: 1.00 [reference], 1.12 [0.78–1.60], 1.65 [1.18–2.30], and 1.56 [1.11–2.19] for UACR of ≤6.9, 7.0–12.7, 12.8–29.9, and ≥30.0 mg/g, respectively), AD (1.00 [reference], 1.20 [0.77–1.86], 1.75 [1.16–2.64], and 1.58 [1.03–2.41], respectively), and VaD (1.00 [reference], 1.03 [0.46–2.29], 1.94 [0.96–3.95], and 2.19 [1.09–4.38], respectively). On the other hand, lower eGFR level was marginally associated with greater risk of VaD, but not AD. Subjects with UACR ≥12.8 mg/g and eGFR of

BackgroundAmong patients with ischemic stroke and atrial fibrillation, which ones are at high risk of recurrent stroke is unclear. This study aimed to determine whether left atrial size was associated with long‐term risk of stroke recurrence in patients with nonvalvular atrial fibrillation. Methods and ResultsIn this multicenter prospective cohort study, nonvalvular atrial fibrillation patients hospitalized for acute ischemic stroke were enrolled and followed up after discharge. Indexed‐left atrial diameter was obtained by dividing left atrial diameter by body surface area. Cause‐specific and subdistribution hazard ratios of recurrent stroke were estimated by Cox proportional hazards and Fine–Gray models, respectively. Risk prediction was evaluated by integrated discrimination improvement and net reclassification improvement. In total, 1611 patients (77.8±10.2 [mean±SD] years, 44.5% female) were included. During follow‐up for 2.40±1.63 (mean±SD) years, 251 patients had recurrent stroke and 514 patients died. An increased indexed‐left atrial diameter (per 1 cm/m2) was significantly associated with elevated risk of stroke recurrence (hazard ratio 1.60, 95% CI 1.30–1.98). The association was maintained when death was regarded as the competing risk and in 1464 patients who were treated with anticoagulants (hazard ratio 1.59, 95% CI 1.27–2.00). Risk prediction for recurrent stroke was significantly improved by adding indexed‐left atrial diameter to the baseline model composed of the factors in the CHADS2 score or those in the CHA2DS2‐VASc score. ConclusionThese findings suggest that left atrial enlargement is associated with an increased risk of recurrent stroke in nonvalvular atrial fibrillation patients with ischemic stroke.

Background: Cardiovascular disease (CVD) is a leading cause of death in Japan. The present study aimed to develop new risk prediction models for long-term risks of all-cause and cardiovascular death in patients with chronic phase CVD. Methods: Among the subjects registered in the BioBank Japan database, 15,058 patients aged ≥40 years with chronic ischemic CVD (ischemic stroke or myocardial infarction) were divided randomly into a derivation cohort (n = 10,039) and validation cohort (n = 5019). These subjects were followed up for 8.55 years in median. Risk prediction models for all-cause and cardiovascular death were developed using the derivation cohort by Cox proportional hazards regression. Their prediction performances for 5-year risk of mortality were evaluated in the validation cohort. Results: During the follow-up, all-cause and cardiovascular death events were observed in 2962 and 962 patients from the derivation cohort and 1536 and 481 from the validation cohort, respectively. Risk prediction models for all-cause and cardiovascular death were developed from the derivation cohort using ten traditional cardiovascular risk factors, namely, age, sex, CVD subtype, hypertension, diabetes, total cholesterol, body mass index, current smoking, current drinking, and physical activity. These models demonstrated modest discrimination (c-statistics, 0.703 for all-cause death; 0.685 for cardiovascular death) and good calibration (Hosmer-Lemeshow χ2-test, P = 0.17 and 0.15, respectively) in the validation cohort. Conclusions: We developed and validated risk prediction models of all-cause and cardiovascular death for patients with chronic ischemic CVD. These models would be useful for estimating the long-term risk of mortality in chronic phase CVD.

Background: Gastrointestinal (GI) hemorrhage is a potentially serious complication of acute stroke, but its incidence appears to be decreasing. The aim of this study was to elucidate the etiology of GI bleeding and its impact on clinical outcomes in patients with acute ischemic stroke in recent years. Methods: Using the database of the Fukuoka Stroke Registry, 6,529 patients with acute ischemic stroke registered between June 2007 and December 2012 were included in this study. We recorded clinical data including any previous history of peptic ulcer, prestroke drug history including the use of antiplatelets, anticoagulants, steroids and nonsteroidal anti-inflammatory drugs (NSAIDs), and poststroke treatment with suppressing gastric acidity. GI bleeding was defined as any episode of hematemesis or melena on admission or during hospitalization. The cause and origin of bleeding were diagnosed endoscopically. Logistic regression analysis was used to identify risk factors for GI bleeding and its influence on deteriorating neurologic function, death, and poor outcome. Results: GI bleeding occurred in 89 patients (1.4%) under the condition that 66% of the total patients received acid-suppressing agents after admission. Multivariate analysis revealed that GI bleeding was associated with the absence of dyslipidemia (p = 0.03), a previous history of peptic ulcer (p Conclusions: GI bleeding infrequently occurred in patients with acute ischemic stroke, which was mostly due to etiologies other than peptic ulcer. GI bleeding was associated with poor clinical outcomes including neurologic deterioration, in-hospital mortality, and poor functional outcome.

Although plasma C-reactive protein (CRP) is elevated in response to inflammation caused by brain infarction, the association of CRP with clinical outcomes after acute ischemic stroke remains uncertain. This study examined whether plasma high-sensitivity CRP (hsCRP) levels at onset were associated with clinical outcomes after acute ischemic stroke independent of conventional risk factors and acute infections after stroke.We prospectively included 3653 patients with first-ever ischemic stroke who had been functionally independent and were hospitalized within 24 h of onset. Plasma hsCRP levels were measured on admission and categorized into quartiles. The association between hsCRP levels and clinical outcomes, including neurological improvement, neurological deterioration, and poor functional outcome (modified Rankin scale ≥3 at 3 months), were investigated using a logistic regression analysis.Higher hsCRP levels were significantly associated with unfavorable outcomes after adjusting for age, sex, baseline National Institutes of Health Stroke Scale score, stroke subtype, conventional risk factors, intravenous thrombolysis and endovascular therapy, and acute infections during hospitalization (multivariate-adjusted odds ratios [95% confidence interval] in the highest quartile versus the lowest quartile as a reference: 0.80 [0.65-0.97] for neurological improvement, 1.72 [1.26-2.34] for neurological deterioration, and 2.03 [1.55-2.67] for a poor functional outcome). These associations were unchanged after excluding patients with infectious diseases occurring during hospitalization, or those with stroke recurrence or death. These trends were similar irrespective of stroke subtypes or baseline stroke severity, but more marked in patients aged

Differences in DNA collection protocols may be a potential confounder in epigenome-wide association studies (EWAS) using a large number of blood specimens from multiple biobanks and/or cohorts. Here we show that pre-analytical procedures involved in DNA collection can induce systematic bias in the DNA methylation profiles of blood cells that can be adjusted by cell-type composition variables. In Experiment 1, whole blood from 16 volunteers was collected to examine the effect of a 24 h storage period at 4°C on DNA methylation profiles as measured using the Infinium HumanMethylation450 BeadChip array. Our statistical analysis showed that the P-value distribution of more than 450,000 CpG sites was similar to the theoretical distribution (in quantile-quantile plot, λ = 1.03) when comparing two control replicates, which was remarkably deviated from the theoretical distribution (λ = 1.50) when comparing control and storage conditions. We then considered cell-type composition as a possible cause of the observed bias in DNA methylation profiles and found that the bias associated with the cold storage condition was largely decreased (λ adjusted = 1.14) by taking into account a cell-type composition variable. As such, we compared four respective sample collection protocols used in large-scale Japanese biobanks or cohorts as well as two control replicates. Systematic biases in DNA methylation profiles were observed between control and three of four protocols without adjustment of cell-type composition (λ = 1.12-1.45) and no remarkable biases were seen after adjusting for cell-type composition in all four protocols (λ adjusted = 1.00-1.17). These results revealed important implications for comparing DNA methylation profiles between blood specimens from different sources and may lead to discovery of disease-associated DNA methylation markers and the development of DNA methylation profile-based predictive risk models.

The benefit of intravenous recombinant tissue plasminogen activator (rt-PA) therapy for very old patients with acute ischemic stroke remains unclear. The aim of this study was to elucidate the efficacy and safety of intravenous rt-PA therapy for patients over 80 years old.Of 13,521 stroke patients registered in the Fukuoka Stroke Registry in Japan from June 1999 to February 2013, 953 ischemic stroke patients who were over 80 years old, hospitalized within 3 h of onset, and not treated with endovascular therapy were included in this study. Among them, 153 patients were treated with intravenous rt-PA (0.6 mg/kg). For propensity score (PS)-matched case-control analysis, 148 patients treated with rt-PA and 148 PS-matched patients without rt-PA therapy were selected by 1:1 matching with propensity for using rt-PA. Clinical outcomes were neurological improvement, good functional outcome at discharge, in-hospital mortality, and hemorrhagic complications (any intracranial hemorrhage [ICH], symptomatic ICH, and gastrointestinal bleeding).In the full cohort of 953 patients, rt-PA use was associated positively with neurological improvement and good functional outcome, and negatively with in-hospital mortality after adjustment for multiple confounding factors. In PS-matched case-control analysis, patients treated with rt-PA were still at lower risk for unfavorable clinical outcomes than non-treated patients (neurological improvement, odds ratio 2.67, 95% confidence interval 1.61-4.40; good functional outcome, odds ratio 2.23, 95% confidence interval 1.16-4.29; in-hospital mortality, odds ratio 0.30, 95% confidence interval 0.13-0.65). There was no significant association between rt-PA use and risk of hemorrhagic complications in the full and PS-matched cohorts.Intravenous rt-PA therapy was associated with improved clinical outcomes without significant increase in risk of hemorrhagic complications in very old patients (aged>80 years) with acute ischemic stroke.

Endpoint adjudication committees (EPAC) are widely used in clinical trials. The aim of the present analysis is to assess the effects of the endpoint adjudication process on the main findings of the ADVANCE trial (Trial registration: ClinicalTrials.gov NCT00145925).The ADVANCE trial was a multicentre, 2 × 2 factorial randomised controlled trial of blood pressure lowering and intensive blood glucose control in 11140 patients with type 2 diabetes. Primary outcomes were major macrovascular (nonfatal myocardial infarction, nonfatal stroke and cardiovascular death) and microvascular (new or worsening nephropathy and retinopathy) events. Suspected primary outcomes were initially reported by the investigators at the 215 sites with subsequent adjudication by the EPAC. The EPAC also adjudicated upon potential events identified directly by ongoing screening of all reported events. Over a median follow-up of 5 years, the site investigators reported one or more primary outcomes among 2443 participants. After adjudication these events were confirmed for 2077 (85%) with 48 further events added through the EPAC-led database screening process. The estimated relative risk reductions (95% confidence intervals) in the primary outcome for the blood pressure lowering comparison were 8% (-1 to 15%) based on the investigator-reported events and 9% (0 to 17%) based on the EPAC-based events (P for homogeneity = 0.70). The corresponding findings for the glucose comparison were 8% (1 to 15%) and 10% (2% to 18%) (P for homogeneity = 0.60). The effect estimates were also highly comparable when studied separately for macrovascular events and microvascular events for both comparisons (all P for homogeneity>0.6).The endpoint adjudication process had no discernible impact on the main findings in ADVANCE. These data highlight the need for careful consideration of the likely impact of an EPAC on the findings and conclusions of clinical trials prior to their establishment.

Aims To investigate the association between corneal hysteresis and the presence of glaucoma and its subtypes in a general Japanese population. Methods We analysed the data of 2338 Japanese community-dwellers aged =40 years (1059 men, 1279 women) who underwent an eye examination in 2018 as part of the population-based, cross-sectional Hisayama Study. Participants were divided into quartile levels of corneal hysteresis, which had been measured with an ocular response analyzer. Glaucoma was defined based on the International Society of Geographical and Epidemiological Ophthalmology criteria. We conducted a logistic regression analysis to determine the ORs and their 95% CIs for the presence of outcomes according to the corneal hysteresis quartiles. Results Glaucoma was diagnosed in 154 participants: primary open-angle glaucoma (POAG), n=115; primary angle-closure glaucoma, n=17; exfoliation glaucoma, n=21 and secondary glaucoma without exfoliation glaucoma, n=1. After adjustment for confounders, the OR for prevalent glaucoma was significantly increased in the participants in the first corneal-hysteresis quartile compared with those in the fourth quartile (OR: 1.80; 95% CI: 1.03 to 3.17). Regarding glaucoma subtypes, the first-quartile participants had significantly greater likelihoods of the presence of POAG (OR: 1.63; 95% CI: 1.02 to 2.61) and exfoliation glaucoma (OR: 6.49; 95% CI: 1.44 to 29.30) compared with those in the third and fourth quartiles after adjustment for potential confounders. Conclusions These Results demonstrated a significant inverse association between corneal hysteresis and the likelihood of glaucoma, suggesting that the measurement of corneal hysteresis would provide useful information for elucidating the aetiology of glaucoma. [ABSTRACT FROM AUTHOR]