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Aim: To assess the association between plasma amyloid β (Aβ) 42/40, phosphorylated tau (p‐τ)181, glial fibrillary acidic protein (GFAP), or neurofilament light chain (NfL) and the risk of dementia and to determine whether these plasma biomarkers could improve the ability to predict incident dementia in a general older population. Methods: A total of 1346 Japanese community‐dwelling individuals aged ≥65 years without dementia were followed prospectively for 5.0 years. Plasma biomarkers were quantified using a Simoa HD‐X analyzer. A Cox proportional hazards model was used to estimate the hazard ratios of each plasma biomarker level for the risk of dementia. Results: During the follow‐up, 151 participants developed dementia, of whom 108 had Alzheimer disease (AD) and 43 non–Alzheimer dementia (non‐AD). Lower plasma Aβ42/40 levels and higher plasma p‐τ181 levels were significantly associated with developing AD but not non‐AD, whereas significant associations were observed between higher plasma levels of GFAP and NfL and risk of both AD and non‐AD (all P for trend <0.05). In addition, adding these four plasma biomarkers into a model consisting of the total score of the dementia risk model significantly improved the predictive ability for incident dementia. Conclusion: Our findings suggest that plasma Aβ42/40 and p‐τ181 are specific markers of AD, and plasma GFAP and NfL are potential biomarkers for all‐cause dementia in the general Japanese older population. In addition, the measurement of these plasma biomarkers may be a useful and relatively low‐invasive procedure for identifying individuals at high risk for developing dementia in clinical practice. [ABSTRACT FROM AUTHOR]

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 < 0.05). Individuals with retinopathy had significantly higher risk of developing dementia than those without after adjustment for potential confounding factors (HR 1.64, 95% CI 1.19–2.25). Regarding the components of retinopathy, the presence of microaneurysms was significantly associated with a higher multivariable-adjusted HR for incident dementia (HR 1.94, 95% CI 1.37–2.74). Our findings suggest that, in addition to systemic risk factors, retinal microvascular signs from fundus photography provide valuable information for estimating the risk of developing dementia. [ABSTRACT FROM AUTHOR]

Several population-based studies have reported that higher serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are associated with brain morphological changes. However, no population-based studies have examined the relationship between serum NT-proBNP and various regional brain volumes in detail. We here analyzed the brain MRI data of 1 201 community-dwelling Japanese aged ≥65 years. Regional gray matter volumes (GMV) and intracranial volume (ICV) were estimated by applying voxel-based morphometry (VBM) methods. The associations of serum NT-proBNP with regional GMV/ICV were examined by analysis of covariance. The regional gray matter atrophy patterns associated with elevated serum NT-proBNP levels were investigated using VBM without a priori regions of interest. The multivariable-adjusted means of the frontal, temporal, hippocampal, parahippocampal, and entorhinal GMV/ICV decreased significantly with elevated serum NT-proBNP levels (all p for trend and q values of false discovery rate correction < .05). In VBM, elevated serum NT-proBNP levels were correlated with atrophy of the bilateral hippocampi, bilateral amygdalas, bilateral parahippocampal gyri, bilateral entorhinal areas, bilateral fusiform gyri, left middle temporal gyrus, left inferior temporal gyrus, right central operculum, right posterior orbital gyrus, bilateral middle frontal gyri, anterior cingulate gyrus and bilateral medial frontal cortices. In a sensitivity analysis excluding 254 participants with mild cognitive impairment or dementia, serum NT-proBNP levels were correlated with atrophy of the bilateral hippocampi, bilateral amygdalas, bilateral parahippocampal gyri, bilateral fusiform gyri, and left middle frontal gyrus. Our data suggest that elevated serum NT-proBNP levels are associated with gray matter atrophy in brain regions that play an important role in cognitive function. [ABSTRACT FROM AUTHOR]

Background: Autonomic nervous system dysfunction has been reported to be associated with impaired activities of daily living (ADL) among patients with chronic pain, but the association has not been fully addressed in general populations. This study cross‐sectionally investigated the association between autonomic nervous system function and the presence of subjective symptoms affecting ADL in community‐dwelling residents with chronic pain. Methods: A total of 888 residents with chronic pain, aged 40–79 years, who underwent a health examination in 2017–2018 were included. Based on heart rate variability measured by fingertip pulse wave, the standard deviation of normal‐to‐normal intervals (SDNN), root mean square of successive RR interval differences (RMSSD), low frequency (LF) power, and high frequency (HF) power were calculated. Symptoms affecting ADL were defined as those scoring ≥1 on the modified Rankin Scale. Odds ratios (ORs) and their 95% confidence intervals (CIs) for symptoms affecting ADL were estimated using a logistic regression analysis. Results: The overall prevalence of symptoms affecting ADL was 39.4%. The ORs for symptoms affecting ADL increased significantly per 1‐standard‐deviation decrement in log‐transformed SDNN (OR 1.23 [95% CI 1.06–1.44]), RMSSD (1.25 [1.08–1.45]), LF power (1.29 [1.11–1.52]), and HF power (1.29 [1.11–1.51]) after adjusting for age, sex, education, hypertension, diabetes, serum total cholesterol level, body mass index, past medical history, current smoking, current drinking, exercise, depressive symptoms, and pain intensity. Conclusions: Decreased heart rate variability was associated with the presence of symptoms affecting ADL among individuals with chronic pain in a Japanese community. Significance: Decrease in heart rate variability was associated with the presence of symptoms affecting ADL among individuals with chronic pain in a Japanese community. This article could help scientists understand the significance of autonomic nervous system dysfunction in the pathology of chronic pain. Approaches that target autonomic nervous system dysfunction may be an option to relieve or prevent symptoms affecting ADL for chronic pain sufferers. [ABSTRACT FROM AUTHOR]

Background: Enlarged perivascular spaces (EPVS) of the brain may be involved in dementia, such as Alzheimer's disease and cerebral small vessel disease (CSVD). Hypertension has been reported to be a risk factor for dementia and CSVD, but the association between blood pressure (BP) and perivascular spaces is still unclear. The aim of this study was to determine the association between BP and EPVS volumes and to examine the interactions of relevant factors. Methods: A total of 9296 community-dwelling subjects aged ≥65 years participated in a brain magnetic resonance imaging and health status screening examination. Perivascular volume was measured using a software package based on deep learning that was developed in-house. The associations between BP and EPVS volumes were examined by analysis of covariance and multiple regression analysis. Results: Mean EPVS volumes increased significantly with rising systolic and diastolic BP levels (P for trend =.003, P for trend<.001, respectively). In addition, mean EPVS volumes increased significantly for every 1-mmHg-increment in systolic and diastolic BPs (both P values <.001). These significant associations were still observed in the sensitivity analysis after excluding subjects with dementia. Conclusions: The present data suggest that higher systolic and diastolic BP levels are associated with greater EPVS volumes in cognitively normal older people. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that decreased gait speed is associated with impaired cognitive function. However, whether this association is equivalent across ages or genders in the older population remains unclear. Thus, we examined the association between mild cognitive impairment (MCI) and gait speed emphasising the influence of age and gender. Methods: Overall, 8233 Japanese participants aged ≥65 years were enrolled in this cross‐sectional study between 2016 and 2018. After stratification by gender and age group, the participants' gait speeds were divided into quintiles, and the difference in MCI prevalence at each gait speed quintile was calculated. Logistic regression analyses were performed to assess the odds of MCI for each quintile and to assess the influence of age and gender. Results: Males had a consistently higher prevalence of MCI than females. The odds of MCI were increased as gait speed decreased. Logistic regression analyses revealed that in the multivariable‐adjusted model 2, the odds ratios (95% confidence interval; CI) for MCI were 2.02 (1.47–2.76) for females and 1.75 (1.29–2.38) for males in the slowest gait speed quintiles compared to the fastest quintile. In the stratified analyses, only males showed an age‐dependent increase in the associations between gait speed and MCI, while females exhibited comparable associations across age groups. Conclusions: Reduced gait speed was associated with increased odds of MCI, and this association may vary according to gender and age. Therefore, gait speed could serve as a valuable screening tool for MCI, with gender‐ and age‐dependent clinical implications. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association of white matter lesions volume (WMLV) levels with dementia risk and the association between dementia risk and the combined measures of WMLV and either total brain atrophy or dementia‐related gray matter atrophy in a general older population. Methods: One thousand one hundred fifty‐eight Japanese dementia‐free community‐residents aged ≥65 years who underwent brain magnetic resonance imaging were followed for 5.0 years. WMLV were segmented using the Lesion Segmentation Toolbox. Total brain volume (TBV) and regional gray matter volume were estimated by voxel‐based morphometry. The WMLV‐to‐intracranial brain volume ratio (WMLV/ICV) was calculated, and its association with dementia risk was estimated using Cox proportional hazard models. Total brain atrophy, defined as the TBV‐to‐ICV ratio (TBV/ICV), and dementia‐related regional brain atrophy defined based on our previous report were calculated. The association between dementia risk and the combined measures of WMLV/ICV and either total brain atrophy or the number of atrophied regions was also tested. Results: During the follow‐up, 113 participants developed dementia. The risks of dementia increased significantly with higher WMLV/ICV levels. In addition, dementia risk increased additively both in participants with higher WMLV/ICV levels and lower TBV/ICV levels and in those with higher WMLV/ICV levels and a higher number of dementia‐related brain regional atrophy. Conclusion: The risk of dementia increased significantly with higher WMLV/ICV levels. An additive increment in dementia risk was observed with higher WMLV/ICV levels and lower TBV/ICV levels or a higher number of dementia‐related brain regional atrophy, suggesting the importance of prevention or control of cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Background: Poor family functioning has been reported to be associated with the severity of chronic pain in outpatients, but the association has not been fully addressed in general populations. The present study aimed to examine the association between family dysfunction levels and the presence of chronic pain in a community‐dwelling Japanese population. Methods: A total of 2598 participants aged ≥40 years were classified as having healthy, borderline or unhealthy family functioning. Chronic pain was defined as subjective pain for three months or longer, and further classified by pain intensity, the number of chronic pain sites, pain duration and the extent of pain spread. A logistic regression model was used to compute the odds ratios (ORs) for chronic pain outcomes. Results: The prevalence of chronic pain was 49%. The age‐ and sex‐adjusted prevalence of total and severe chronic pain were increased significantly with increasing family dysfunction levels (all p for trend <0.01). After adjusting for sociodemographic, physical, social and family structure factors, the ORs (95% confidence intervals [CI]) for having chronic pain among borderline and unhealthy groups were 1.20 (1.01–1.44) and 1.43 (1.15–1.79), respectively, as compared with a healthy family function group. The association was stronger among people who were employed and those who were living with their children. In addition, the ORs for severe chronic pain increased significantly with increasing levels of family dysfunction. Conclusions: The family dysfunction level was positively associated with the presence as well as the severity of chronic pain in a community‐dwelling population. Significance: A biopsychosocial burden due to family relationships could worsen the clinical presentation of pain. Social support or family therapy for dysfunctional families would be a potential initiative for the prevention or management of chronic pain. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to describe changes in physical activity volumes and sedentary time over 3 years in the middle-aged and older Japanese population. Methods: Study participants included 1151 Japanese community-dwelling residents aged ≥40 years in 2009 who underwent 2 sets of health examinations (2009 and 2012). Using a triaxial accelerometer, longitudinal changes in sedentary time, light physical activity volume, moderate to vigorous physical activity volume, number of steps, and total physical activity volume were evaluated according to sex, age (40–49, 50–59, 60–69, 70–79, and ≥80 y), and obese (nonobese and obese) categories. Results: Sedentary time significantly increased, and all physical activity volumes significantly decreased among all participants. Although most variables did not change significantly in the 40–49 and 50–59 year age categories, similar changes as all participants were observed across all other categories. In the correlation analyses, changes in sedentary time correlated, at most, only modestly for each change in physical activity volumes, indicating that increased physical activity volume does not always lead to decreased sedentary time, and vice versa. Conclusions: Strategies to reduce sedentary time and promote physical activity are needed in Japan, particularly for people aged ≥60 years. [ABSTRACT FROM AUTHOR]

Abstract: Chronic low back pain (CLBP) is the leading cause of years lived with disability. Recently, it has been reported that CLBP is associated with alterations in the central nervous system. The present study aimed to investigate the association between CLBP and regional brain atrophy in an older Japanese population. A total of 1106 community-dwelling participants aged ≥65 years underwent brain magnetic resonance imaging scans and a health examination in 2017 to 2018. We used the FreeSurfer software for the analysis of brain magnetic resonance imaging. Chronic pain was defined as subjective pain for ≥3 months. Participants were divided into 3 groups according to the presence or absence of chronic pain and the body part that mainly suffered from pain: a "no chronic pain (NCP)" group (n = 541), "CLBP" group (n = 189), and "chronic pain in body parts other than the lower back (OCP)" group (n = 376). The brain volumes of the ventrolateral and dorsolateral prefrontal cortex, the posterior cingulate gyrus, and the amygdala were significantly lower in the CLBP group than in the NCP group after adjustment for sociodemographic, physical, and lifestyle factors and depressive symptoms. In addition, the left superior frontal gyrus was identified as a significant cluster by the Query, Design, Estimate, Contrast interface. There were no significant differences in the brain volumes of pain-related regions between the NCP and the OCP groups. The present study suggests that CLBP is associated with lower brain volumes of pain-related regions in a general older population of Japanese. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Rationale: Several Western studies have reported that participants with preserved ratio impaired spirometry (PRISm) have higher risks of airflow limitation (AFL) and death. However, evidence in East Asian populations is limited. Objectives: To investigate the relationship between PRISm and the risks of death and incident AFL in a Japanese population. Methods: A total of 3,032 community-dwelling Japanese participants aged ⩾40 years were seen in follow-up for a median of 5.3 years by annual spirometry examinations. Participants were classified into lung function categories at baseline as follows: normal spirometry (FEV1/FVC ⩾0.70 and FEV1 ⩾80% predicted), PRISm (⩾0.70 and <80%), AFL Global Initiative for Chronic Obstructive Lung Disease 1 (<0.70 and ⩾80%), and AFL Global Initiative for Chronic Obstructive Lung Disease 2-4 (<0.70 and <80%). Hazard ratios (HRs) and their 95% confidence intervals were computed using a Cox proportional hazards model. Measurements and Main Results: During the follow-up period, 131 participants died, 22 of whom died of cardiovascular disease, and 218 participants developed AFL. When examining the prognosis of each baseline lung function category, participants with PRISm had higher risks of all-cause death (HR, 2.20; 95% confidence interval, 1.35-3.59) and cardiovascular death (HR, 4.07; 1.07-15.42) than those with normal spirometry after adjusting for confounders. Moreover, the multivariable-adjusted risk of incident AFL was greater in participants with PRISm than in those with normal spirometry (HR, 2.48; 1.83-3.36). Conclusions: PRISm was associated with higher risks of all-cause and cardiovascular death and a greater risk of the development of AFL in a Japanese community. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the association between diabetes and gray matter atrophy patterns in a general older Japanese population. RESEARCH DESIGN AND METHODS: In 2012, a total of 1,189 community-dwelling Japanese aged ≥65 years underwent brain MRI scans. Regional gray matter volumes (GMV) and intracranial volume (ICV) were measured by applying voxel-based morphometry (VBM) methods. The associations of diabetes and related parameters with the regional GMV/ICV were examined using an ANCOVA. The regional gray matter atrophy patterns in the subjects with diabetes or elevated fasting plasma glucose (FPG) or 2-h postload glucose (2hPG) levels were investigated using VBM. RESULTS: Subjects with diabetes had significantly lower mean values of GMV/ICV in the frontal lobe, temporal lobe, insula, deep gray matter structures, and cerebellum than subjects without diabetes after adjusting for potential confounders. A longer duration of diabetes was also significantly associated with lower mean values of GMV/ICV in these brain regions. The multivariable-adjusted mean values of the temporal, insular, and deep GMV/ICV decreased significantly with elevating 2hPG levels, whereas higher FPG levels were not significantly associated with GMV/ICV of any brain regions. In the VBM analysis, diabetes was associated with gray matter atrophy in the bilateral superior temporal gyri, right middle temporal gyrus, left inferior temporal gyrus, right middle frontal gyrus, bilateral thalami, right caudate, and right cerebellum. CONCLUSIONS: The current study suggests that a longer duration of diabetes and elevated 2hPG levels are significant risk factors for gray matter atrophy in various brain regions. [ABSTRACT FROM AUTHOR]

Background: Little is known about the influence of serum level of soluble triggering receptor expressed on myeloid cells 2 (sTREM2), which is a soluble type of an innate immune receptor expressed on the microglia, on the association of the daily sleep duration with the risk of dementia. Methods: A total of 1230 Japanese community‐residents aged 60 and older without dementia were followed prospectively for 10 years (2002–2012). Serum sTREM2 levels were divided into two groups using the median value (334.8 pg/ml). Self‐reported daily sleep duration was grouped into three categories of <5.0, 5.0–7.9, and ≥8.0 h. A Cox proportional hazards model was used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) of daily sleep duration on the risk of dementia according to serum sTREM2 levels. Results: During the follow‐up, 262 subjects developed dementia. In subjects with low serum sTREM2 levels, subjects with ≥8.0 h of daily sleep had a significantly greater risk of dementia (multivariable‐adjusted HR 2.05 [95% CI 1.32–3.19]) than those with 5.0–7.9 h of daily sleep, but those with <5.0 h did not. In contrast, the risk of dementia increased significantly in subjects with both <5.0 (1.95 [1.03–3.68]) and ≥8.0 h of daily sleep (1.48 [1.06–2.07]) in the subjects with high serum sTREM2 levels. Conclusions: The influence of daily sleep duration on risk of dementia differed according to serum sTREM2 levels in the older Japanese population. Short daily sleep may be associated with greater risk of dementia only in subjects with a high serum sTREM2 level. [ABSTRACT FROM AUTHOR]

Objective: To assess the association of regional grey matter atrophy with dementia risk in a general older Japanese population.Methods: We followed 1158 dementia-free Japanese residents aged ≥65 years for 5.0 years. Regional grey matter volume (GMV) at baseline was estimated by applying voxel-based morphometry methods. The GMV-to-total brain volume ratio (GMV/TBV) was calculated, and its association with dementia risk was estimated using Cox proportional hazard models. We assessed whether the predictive ability of a model based on known dementia risk factors could be improved by adding the total number of regions with grey matter atrophy among dementia-related brain regions, where the cut-off value for grey matter atrophy in each region was determined by receiver operating characteristic curves.Results: During the follow-up, 113 participants developed all-cause dementia, including 83 with Alzheimer's disease (AD). Lower GMV/TBV of the medial temporal lobe, insula, hippocampus and amygdala were significantly/marginally associated with higher risk of all-cause dementia and AD (all p for trend ≤0.08). The risks of all-cause dementia and AD increased significantly with increasing total number of brain regions exhibiting grey matter atrophy (both p for trend <0.01). Adding the total number of regions with grey matter atrophy into a model consisting of known risk factors significantly improved the predictive ability for AD (Harrell's c-statistics: 0.765-0.802; p=0.02).Conclusions: Our findings suggest that the total number of regions with grey matter atrophy among the medial temporal lobe, insula, hippocampus and amygdala is a significant predictor for developing dementia, especially AD, in the general older population. [ABSTRACT FROM AUTHOR]

Background: Glucose dysmetabolism is an important risk factor for dementia.Objective: We investigated the associations of diabetes mellitus, the levels of glycemic measures, and insulin resistance and secretion measures with dementia and its subtypes in a cross-sectional study.Methods: In this study, 10,214 community-dwelling participants were enrolled. Hemoglobin A1c (HbA1c), the homeostasis model assessment (HOMA) for insulin resistance (HOMA-IR), the HOMA of percent β-cell function (HOMA-β), and the glycated albumin (GA) was evaluated. The associations of each measure with Alzheimer's disease (AD) and vascular dementia (VaD) were investigated.Results: The multivariable-adjusted odds ratios (ORs) of AD were significantly higher in participants with diabetes mellitus than in those without diabetes (1.46 [95% CI: 1.08-1.97]). Higher HbA1c levels were significantly associated with AD at diabetes (≥6.5%) and even at prediabetes (5.7 %-6.4 %) levels; multivariable-adjusted ORs for AD in participants at the diabetes level were 1.72 (95% CI: 1.19-2.49), and those in participants at the prediabetes level were 1.30 (95% CI: 1.00-1.68), compared with those in normal participants. Moreover, higher GA levels were associated with AD. No associations were observed between the diabetic status or the levels of glycemic measures and VaD. In addition, no significant relationships were observed between insulin resistance and secretion measurements and AD and VaD.Conclusion: Our findings indicate that diabetes mellitus and hyperglycemia are significantly associated with AD, even in individuals at the prediabetes level. [ABSTRACT FROM AUTHOR]

Objectives To investigate the association of loneliness and its component subscales with the risk of dementia in a general Japanese older population. Method A total of 1,141 community-dwelling Japanese residents aged ≥65 years without dementia were prospectively followed up for a median 5.0 years. We evaluated any loneliness and its component subscales—namely, social and emotional loneliness—by using the 6-item de Jong Gierveld Loneliness Scale. Cox proportional hazards models were used to estimate hazard ratios (HRs) of each loneliness type on the risk of dementia controlling for demographic factors, lifestyle factors, physical factors, social isolation factors, and depression. Results During the follow-up, 114 participants developed dementia. The age- and sex-adjusted incidence rate of dementia was significantly greater in participants with any loneliness and emotional loneliness than those without. The multivariable-adjusted HRs (95% confidence intervals) of participants with any loneliness and emotional loneliness on incident dementia were 1.61 (1.08–2.40) and 1.65 (1.07–2.54), respectively, as compared to those without. However, there was no significant association between social loneliness and dementia risk. In subgroup analyses of social isolation factors, excess risks of dementia associated with emotional loneliness were observed in participants who had a partner, lived with someone, or rarely communicated with relatives or friends, but such association was not significant in participants who had no partner, lived alone, or frequently communicated with friends or relatives. Discussion The present study suggested that loneliness, especially emotional loneliness, was a significant risk factor for the development of dementia in the general older population in Japan. [ABSTRACT FROM AUTHOR]

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 < 10, 10–15, and > 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 < 0.05), but not with higher HbA1c levels, after adjusting for age, sex, low education, systolic blood pressure, antihypertensive medication, diabetes mellitus, serum total cholesterol, electrocardiogram abnormalities, body mass index, smoking habits, alcohol drinking habits and regular exercise. These significant associations were still observed in the sensitivity analysis after excluding individuals with mild cognitive impairment and dementia. In addition, increased serum GA levels and the GA : HbA1c ratio levels, but not HbA1c, were closely associated with lower mean values of the TBV : ICV and HV : ICV ratios, irrespective of the presence or absence of diabetes mellitus. Conclusions: The present study suggests that higher serum GA and higher GA : HbA1c ratio are significantly associated with global brain and hippocampal atrophy. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between serum total homocysteine levels (tHcy) and dementia risk.Methods: A total of 1588 Japanese adults aged ≥60 years without dementia were prospectively followed from 2002 to 2012. Cox proportional hazards models and restricted cubic splines were used to estimate the HRs of tHcy levels on the risk of dementia.Results: During the follow-up, 372 subjects developed all-cause dementia; 247 had Alzheimer's disease (AD) and 98 had vascular dementia (VaD). Compared with the lowest tHcy quintile (≤6.4 µmol/L), the multivariable-adjusted HRs (95% CI) of the highest quintile (≥11.5 µmol/L) were 2.28 (1.51-3.43) for all-cause dementia, 1.96 (1.19-3.24) for AD and 2.51 (1.14-5.51) for VaD. In restricted cubic splines, the risk of all-cause dementia steadily increased between approximately 8-15 µmol/L and plateaued thereafter, with a similar non-linear shape observed for AD and VaD (all p for non-linearity ≤0.02). In stratified analyses by the most recognised genetic polymorphism affecting tHcy concentrations (methylenetetrahydrofolate reductase C677T), the positive association of tHcy with all-cause dementia persisted in both non-carriers and carriers of the risk allele, and even tended to be stronger in the former (p for heterogeneity=0.07).Conclusion: High serum tHcy levels are associated with an elevated risk of dementia, AD and VaD in a non-linear manner, such that an exposure-response association is present only within a relatively high range of tHcy levels. Non-genetic factors affecting serum tHcy concentrations may play important roles in tHcy-dementia associations irrespective of the genetic susceptibility for raised tHcy. [ABSTRACT FROM AUTHOR]

We examined the association between serum concentrations of β-alanine, a metabolite of carnosine and anserine, and the risk of dementia in a general population of elderly Japanese persons. In 2007, 1,475 residents of Hisayama, Japan, aged 60–79 years and without dementia were divided into 4 groups according to quartiles of serum β-alanine concentrations (quartile 1, lowest; quartile 4, highest) and followed for a median of 5.3 years. During follow-up, 117 subjects developed all-cause dementia (Alzheimer in 77 cases and vascular dementia in 31). The risk of all-cause dementia decreased with increasing serum β-alanine levels after adjustment for potential confounding factors (quartile 2, hazard ratio (HR) = 0.73 (95% confidence interval (CI): 0.45, 1.18); quartile 3, HR = 0.50 (95% CI: 0.28, 0.89); quartile 4, HR = 0.50 (95% CI: 0.27, 0.92); P = 0.01 for trend). A similar inverse association was observed for Alzheimer disease (quartile 2, HR = 0.78 (95% CI: 0.44, 1.38); quartile 3, HR = 0.53 (95% CI: 0.26, 1.06); quartile 4, HR = 0.53 (95% CI: 0.25, 1.10); P = 0.04 for trend) but not for vascular dementia. We found that higher serum β-alanine levels were significantly associated with lower risks of all-cause dementia and Alzheimer disease. Because serum β-alanine levels reflect intakes of carnosine/anserine, higher intakes of carnosine/anserine might be beneficial for the prevention of dementia. [ABSTRACT FROM AUTHOR]

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 <6 h in sedentary time (odds ratio 1.84, 95% confidence interval 1.02–3.31). This significant association remained after adjusting for overall and central obesity (as measured by body mass index and waist circumference), but weakened after adjusting for dietary energy intake or homeostasis model assessment of insulin resistance. Sedentary time was positively associated with homeostasis model assessment of insulin resistance levels among non‐diabetic participants after adjusted for obesity or energy intake (P for trend <0.01). Conclusions: Longer sedentary time was associated with a higher prevalence of diabetes mellitus in a general Japanese population. Insulin resistance appeared to be mainly involved in this association. These results highlight the importance of public health strategies targeting reductions in sedentary time for the primary prevention of diabetes mellitus. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between serum soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a soluble type of an innate immune receptor expressed on the microglia, and the risk of dementia.Methods: A total of 1,349 Japanese community residents aged 60 and older without dementia were followed prospectively for 10 years (2002-2012). Serum sTREM2 levels were quantified by using an enzyme-linked immunosorbent assay and divided into quartiles. Cox proportional hazards model was used to estimate the hazard ratios (HRs) of serum sTREM2 levels on the risk of dementia.Results: During the follow-up, 300 subjects developed all-cause dementia; 193 had Alzheimer's disease (AD), and 85 had vascular dementia (VaD). The age- and sex-adjusted incidences of all-cause dementia, AD, and VaD elevated significantly with higher serum sTREM2 levels (all p for trend < 0.012). These associations were not altered after adjustment for confounding factors, including high-sensitive C-reactive protein. Subjects with the highest quartile of serum sTREM2 levels had significantly higher multivariable-adjusted risks of developing all-cause dementia, AD, and VaD than those with the lowest quartile (HR = 2.03, 95% confidence interval [CI] = 1.39-2.97, p < 0.001 for all-cause dementia; HR = 1.62, 95% CI = 1.02-2.55, p = 0.04 for AD; HR = 2.85, 95% CI = 1.35-6.02, p = 0.006 for VaD). No significant heterogeneity in the association of serum sTREM2 levels with the development of dementia was observed among the other risk factor subgroups (all p for heterogeneity > 0.11).Interpretation: The present findings suggest a significant association between increased serum sTREM2 levels and the risk of developing all-cause dementia, AD, and VaD in the general elderly Japanese population. ANN NEUROL 2019;85:47-58. [ABSTRACT FROM AUTHOR]