Association between flexibility activity and blood-pressure change among older adults in Japan: A 5-year longitudinal study.

This longitudinal study examined the relationship between flexibility-activity and blood-pressure (BP) change among older adults in Japan. Our study included 452 older adults who took part in our survey in both 2012/2013 and 2017/2018. The seated systolic blood pressure (SBP) and diastolic BP (DBP) were measured both at baseline and at the 5 years follow-up. The frequencies of the different physical activities at baseline were assessed using a questionnaire. A generalized linear mixed model was used to estimate the non-standardized coefficient (B) of BP change associated with flexibility activity, after adjustments for sex, age, body mass index, smoking status, alcohol consumption, antihypertensive medication use, history of heart disease, walking time, and muscle-strengthening activity as a fixed-effect, and area of residence as a random-effect. Higher flexibility-activity frequency was significantly associated with reduced SBP (B = -0.77 [95% confidence intervals = -1.36, -0.18], p for linear trend = 0.01, p for quadratic trend = 0.85) and DBP (-0.33 [-0.71, 0.05], p for linear trend = 0.09, p for quadratic trend = 0.04). Engaging in flexibility activity for 3 days per week was significantly associated with a reduction in DBP (B = -4.16, 95% CI [-7.53, -0.79], p = 0.02) compared with that in the reference group (0 days per week). Interaction tests were not significant between basic variables (sex, age, BMI, and antihypertensive medication) and flexibility. In conclusion, higher flexibility activity frequency was associated with a reduction in BP in older adults. Future longitudinal and interventional studies should examine the effects of flexibility activity on cardiovascular disease prevention.

Associations between dairy consumption and the physical function in Japanese community-dwelling older adults: The Shimane CoHRE study.

OBJECTIVES: We investigated sex differences in the associations between dairy consumption and the physical function among community-dwelling older adults. METHODS: Six hundred and fifty-six older adults (75.6 ± 6.4 years old) participated in this study. Dairy consumption (5-item Likert score) and the physical function (gait speed, handgrip strength, and skeletal muscle mass) were measured. The linear and quadratic associations between dairy consumption and the physical function measures were examined by a multiple linear regression analysis adjusted for covariates. RESULTS: Among women, an increased dairy consumption was significantly linearly associated with greater hand-grip strength and faster gait speed (both p<0.05) after adjusting for covariates. Among men, dairy consumption was not associated with the physical function measures. Dairy consumption was not associated with the muscle mass in either sex. CONCLUSIONS: Increased dairy consumption was associated with a superior physical function in older women.

Additive Effect of Physical Activity and Sedentary Time on Depressive Symptoms in Rural Japanese Adults: A Cross-Sectional Study.

BACKGROUND: Previous studies have reported an additive effect of moderate-to-vigorous physical activity (MVPA) and sedentary time (ST) on depressive symptoms. However, no studies have been conducted in rural community settings. This cross-sectional study investigated whether the additive effect of MVPA and ST was associated with depressive symptoms in rural Japanese adults. METHODS: We identified 2,814 participants from health examinations conducted in Shimane, rural Japan, in 2012 and analyzed data from 1,958 participants. We assessed depressive symptoms using the Zung Self-Rating Depression Scale and measured the total time spent on MVPA and ST using a Japanese short version of the International Physical Activity Questionnaire. Poisson regression analysis examined the prevalence ratios (PR) of depressive symptoms in nine category combinations of MVPA level (no, insufficient, or sufficient MVPA) and ST level (high, moderate, or low ST). RESULTS: A total of 117 (6.0%) participants had depressive symptoms. Compared with the reference category (no MVPA/high ST), multivariate analysis showed that the likelihood of depressive symptoms was significantly lower in the sufficient MVPA/low ST category (PR 0.23; 95% confidence intervals [CI], 0.08-0.66), insufficient MVPA/low ST category (PR 0.37; 95% CI, 0.16-0.86), and insufficient MVPA/moderate ST category (PR 0.39; 95% CI, 0.17-0.90). CONCLUSION: Analysis of the additive effect of MVPA and ST showed that the combinational category of sufficient MVPA and low ST had the lowest prevalence of depressive symptoms in rural Japanese adults. Moderate ST and low ST showed significantly lower likelihoods of depressive symptoms, regardless of insufficient MVPA.

Height loss but not body composition is related to low back pain in community-dwelling elderlies: Shimane CoHRE study.

BACKGROUND: Low back pain (LBP) is a common complaint in the elderly Japanese population. Although previous studies showed that height loss was associated with LBP, it remains unclear whether LBP is associated with body composition. The objective of the present study was to investigate whether body composition and physical characteristics, including height loss, were associated with LBP. METHODS: The present study is retrospectively registered, and the participants were 2212 community-dwelling Japanese people aged over 60 years who participated in the Shimane CoHRE study in 2016. We investigated the presence of LBP, body composition parameters (muscle, fat, body weight, and bone mass), physical characteristics (body height and height loss), chronic diseases, history of fall, smoking, and drinking habits. We examined the relationships of body composition parameters and physical characteristics with point prevalence of LBP using multivariate logistic regression. RESULTS: The point prevalence of LBP was 43.2% in women and 39.5% in men. Logistic regression models showed that body height and body composition were not significantly associated with LBP; however, height loss was associated significantly with LBP in women and men (OR: 1.14, 95% CI: 1.08-1.20 and OR: 1.13, 95% CI: 1.06-1.21, respectively). Hypertension (OR: 1.32, 9 5% CI: 1.04-1.69) and chronic heart disease (OR: 1.57, 95% CI: 1.01-2.43) in women and history of fall (OR: 1.70, 95% CI: 1.13-2.56) and cerebrovascular disease (OR: 1.88, 95% CI: 1.05-3.34) in men were significantly associated with LBP. However, body composition was not associated with LBP in either gender. CONCLUSIONS: The present study demonstrated that height loss, but not body composition, was related to LBP in community-dwelling elderly people. To elucidate the cause of LBP, it is important to consider the relationship with height loss.

Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.

Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.

Whole-exome sequencing of human pancreatic cancers and characterization of genomic instability caused by MLH1 haploinsufficiency and complete deficiency.

Whole-exome sequencing (Exome-seq) has been successfully applied in several recent studies. We here sequenced the exomes of 15 pancreatic tumor cell lines and their matched normal samples. We captured 162,073 exons of 16,954 genes and sequenced the targeted regions to a mean coverage of 56-fold. This study identified a total of 1517 somatic mutations and validated 934 mutations by transcriptome sequencing. We detected recurrent mutations in 56 genes. Among them, 41 have not been described. The mutation rates varied widely among cell lines. The diversity of the mutation rates was significantly correlated with the distinct MLH1 copy-number status. Exome-seq revealed intensive genomic instability in a cell line with MLH1 homozygous deletion, indicated by a dramatically elevated rate of somatic substitutions, small insertions/deletions (indels), as well as indels in microsatellites. Notably, we found that MLH1 expression was decreased by nearly half in cell lines with an allelic loss of MLH1. While these cell lines were negative in conventional microsatellite instability assay, they showed a 10.5-fold increase in the rate of somatic indels, e.g., truncating indels in TP53 and TGFBR2, indicating MLH1 haploinsufficiency in the correction of DNA indel errors. We further analyzed the exomes of 15 renal cell carcinomas and confirmed MLH1 haploinsufficiency. We observed a much higher rate of indel mutations in the affected cases and identified recurrent truncating indels in several cancer genes such as VHL, PBRM1, and JARID1C. Together, our data suggest that MLH1 hemizygous deletion, through increasing the rate of indel mutations, could drive the development and progression of sporadic cancers.

MC4R rs17782313 gene polymorphism was associated with glycated hemoglobin independently of its effect on BMI in Japanese: the Shimane COHRE study.

BACKGROUND: Type 2 diabetes (T2D) is among the leading public health problems in Japan, and glycated hemoglobin (HbA1c) can be used to screen the population for T2D. Gene polymorphisms, known to be associated with obesity, may predispose individuals to T2D. Rs17782313 the melanocortin 4 receptor (MC4R) has shown one of the strongest associations with body mass index (BMI). We conducted a study to investigate whether rs17782313 (TT versus TC + CC) was associated with HbA1c. METHOD: We conducted a cross-sectional study including 1142 Japanese adults (446 men: 64.9 ± 14.4 years and 696 women: 66.7 ± 12.3 years). MC4R rs17782313 was genotyped using fast real-time polymerase chain reaction. RESULTS: TC + CC genotype group showed significantly greater BMI (p = 0.039) and HbA1c (p = 0.001) than TT genotype group after adjustment for gender, age and, for HbA1c, BMI. Further analysis using linear regression analysis confirmed that the effect of MC4R rs17782313 on HbA1c (ß = 0.08; p = 0.003) was independent of the effect age, gender, BMI, low density lipoprotein cholesterol, homeostasis model assessment of insulin resistance and of beta cell function. This significant independent association was similarly noticed in non-obese (ß = 2.82; p = 0.005) subgroups. CONCLUSION: MC4R rs17782313 was associated with obesity and could confer a certain susceptibility to T2D that could be independent of its pro-obesity effect.

Association between different types of physical activity and occupational stress in Japanese workers: a cross-sectional study.

This cross-sectional study investigated the association between different types of physical activity (PA) and occupational psychological and physical stress responses among workers in Japan. Stress responses were assessed using the Brief Job Stress Questionnaire. Work-related PA (time spent sitting, sitting bouts, standing, walking, engaging in heavy labor, and moderate-to-vigorous PA [MVPA]) and exercise-based PA (frequencies [times/week] of flexibility and muscle-strengthening activity, and walking) were measured using a questionnaire. Multiple linear regression was performed to examine the association between each type of PA and stress responses. Participants who engaged in >108 min/day of work-related MVPA exhibited a statistically significant association with higher psychological stress responses when compared to those who engaged in 0-42 min/day of work-related MVPA. For exercise-based PA, participants who engaged in flexibility activity or walking five or more times/week, or muscle-strengthening activity one to three times/week, demonstrated significantly lower psychological stress responses compared to those who did not exercise. Participants who engaged in flexibility activity five or more times/week demonstrated significantly lower physical stress responses compared to those who did not exercise. This study suggests that work-related MVPA is associated with higher psychological stress responses, while exercise-based PA is associated with lower psychological or physical stress responses.

Combined associations of regular exercise and work-related moderate-to-vigorous physical activity with occupational stress responses: a cross-sectional study.

Objective: The association between work-related moderate-to-vigorous physical activity (MVPA) and higher levels of stress response is recognized, but whether this association is moderated by regular exercise remains unclear. This cross-sectional study investigated whether exercise-based physical activity (PA) associates with lower levels of stress responses moderated by work-related MVPA. Methods: The study participants comprised 863 workers from 35 small and medium-sized enterprises in Shimane prefecture, Japan, collected through convenient sampling from April 2021 to August 2022. The Brief Job Stress Questionnaire was used to assess stress responses. Work-related MVPA and exercise-based PA were measured using questionnaires. Multiple linear regression was used to analyze the combined variables of work-related MVPA and exercise-based PA. The reference group had no weekly exercise-based PA and >60 min of work-related MVPA. Results: When work-related MVPA exceeded 60 min/day, flexibility activity or walking for ≥5 days/week (B = -3.53, 95% CI = -5.96, -1.11; B = -2.53, 95% CI = -4.90, -0.16) and muscle-strengthening activity 1-3 times/week (B = -3.52, 95% CI = -6.91, -0.12) were significantly associated with lower psychological stress response. Flexibility activity (B = -1.74, 95% CI = -3.01, -0.46) showed a similar link with physical stress response. When work-related MVPA was below 60 min/day, flexibility activity (B = -3.23, 95% CI = -6.01, -0.44; B = -3.29, 95% CI = -5.94, -0.63) or walking (B = -4.03, 95% CI = -6.62, -1.45; B = -3.10, 95% CI = -5.76, -0.44) practice 1-4 times/week and ≥5 times/week was significantly associated with lower psychological stress response. Conclusion: Exercise-based PA greatly and consistently associates with a lower level of stress responses moderated by work-related MVPA.

A genome-wide association study identifies a locus associated with knee extension strength in older Japanese individuals.

Sarcopenia is a common skeletal muscle disease in older people. Lower limb muscle strength is a good predictive value for sarcopenia; however, little is known about its genetic components. Here, we conducted a genome-wide association study (GWAS) for knee extension strength in a total of 3452 Japanese aged 60 years or older from two independent cohorts. We identified a significant locus, rs10749438 which is an intronic variant in TACC2 (transforming acidic coiled-coil-containing 2) (P = 4.2 × 10-8). TACC2, encoding a cytoskeleton-related protein, is highly expressed in skeletal muscle, and is reported as a target of myotonic dystrophy 1-associated splicing alterations. These suggest that changes in TACC2 expression are associated with variations in muscle strength in older people. The association was consistently observed in young and middle-aged subjects. Our findings would shed light on genetic components of lower limb muscle strength and indicate TACC2 as a potential therapeutic target for sarcopenia.

Changes in masticatory performance and the new onset of diabetes mellitus in older adults: a 5-year longitudinal study.

Objective: Although masticatory performance is affected by age-related reduction in number of teeth (or treatment), the relationship between longitudinal changes in masticatory performance and diabetes mellitus is unknown. This longitudinal study investigated the association between changes in masticatory performance and new-onset diabetes mellitus among community-dwelling Japanese older adults. Methods: The data of 214 older adults living in Ohnan Town, Shimane, Japan, who participated in two surveys conducted between 2012 and 2017 were analyzed. Diabetes mellitus was defined as a hemoglobin A1c level ≥ 6.5% or self-reported diabetes mellitus. The masticatory performance (measured by number of gummy jelly pieces collected after chewing) was evaluated by dental hygienists. Masticatory performance was categorized into two groups (high or low) based on the median in each survey; further, four groups (Group A: remained consistently high, Group B: changed from low to high, Group C: remained consistently low, Group D: changed from high to low) were used to determine longitudinal changes in masticatory performance. Logistic regression was used to analyze the association between changes in masticatory performance and new-onset diabetes mellitus. Results: Overall, 10.3% of participants had diabetes mellitus at the follow-up survey. Multivariate analysis showed that Group D (odds ratio 8.69, 95% confidence interval 1.98-38.22) was positively associated with the development of diabetes mellitus compared with Group A after adjusting for sex, age, body mass index, alcohol consumption, physical activity, and eating speed. Conclusions: Deteriorating masticatory performance for 5 years may cause diabetes mellitus among older adults.

Fast Eating Speed Could Be Associated with HbA1c and Salt Intake Even after Adjusting for Oral Health Status: A Cross-Sectional Study.

This study aimed to examine the relationship between eating speed and hemoglobin A1c (HbA1c), considering the number of teeth, using cross-sectional health examination data from community-dwelling older individuals in Japan. We used data from the Center for Community-Based Healthcare Research and Education Study in 2019. We collected data on gender, age, body mass index, blood test results, Salt intake, bone mineral density, body fat percentage, muscle mass, basal metabolic rate, number of teeth, and lifestyle information. Eating speed was evaluated subjectively as fast, normal, or slow. Overall, 702 participants were enrolled in the study and 481 participants were analyzed. Multivariate logistic regression analysis revealed a significant association between fast eating speed and being a male (odds ratio [95% confidence interval]: 2.15 [1.02-4.53]), HbA1c (1.60 [1.17-2.19]), salt intake (1.11 [1.01-1.22]), muscle mass (1.05 [1.00-1.09]), and enough sleep (1.60 [1.03-2.50]). Fast eating may be associated with overall health and lifestyle. The characteristics of fast eaters, after taking oral information into consideration, tended to increase the risk of type 2 diabetes, renal dysfunction, and hypertension. Dental professionals should provide dietary and lifestyle guidance to fast eaters.

Association of the number of remaining teeth with kidney function in community-dwelling healthy older adults: a cross-sectional study.

Objectives: Although a few studies have investigated the relationship between kidney and oral function (number of remaining teeth), their results remain inconclusive. Therefore, this study aimed to investigate the relationship between kidney function and oral health in community-dwelling healthy elderlies and examine the factors associated with kidney function. Materials and Methods: We used cross-sectional data from the Shimane prefecture cohort recruited by the Center for Community-Based Health Research and Education in 2019. We collected clinical data on dental status, background factors and kidney function (estimated glomerular filtration rate [eGFR], mL/min/1.73 m2 and creatinine levels, mg/dL). Results: The study enrolled 481 participants, whose mean age was 66.7±7.4 years, and 223 (46.4%) participants were men. Multivariate analysis revealed significant correlations between eGFR (B=0.17, P=0.04), creatinine (B=-0.54, P<0.01), and the number of remaining teeth. The number of remaining teeth was associated with creatinine and eGFR, which are indicators of kidney function. Conclusion: This study suggests that preserving the teeth may prevent decline in kidney function. Dental professionals should provide instructions and professional care to reduce the risk of systemic diseases such as kidney dysfunction.

Neither Trimethylamine-N-Oxide nor Trimethyllysine Is Associated with Atherosclerosis: A Cross-Sectional Study in Older Japanese Adults.

Recent evidence suggests that trimethylamine-N-oxide (TMAO), a metabolite of L-carnitine and choline, is linked to atherosclerosis and cardiovascular diseases. As TMAO content is very high in fish, we raised the following question: why do Japanese people, who consume lots of fish, show a low risk of atherosclerosis? To address this question, we investigated the effects of TMAO and other L-carnitine-related metabolites on carotid intima-media thickness (IMT). Participants were recruited from a small island and a mountainous region. Plasma L-carnitine, γ-butyrobetaine (γBB), TMAO, trimethyllysine (TML), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels were measured using liquid or gas chromatography-mass spectrometry. Plasma L-carnitine concentration was higher in men than in women. TMAO and TML were significantly higher in the residents of the island than in the mountainous people. In multiple linear regression analyses in all participants, TML showed a significant inverse association with max-IMT and plaque score (PS), whereas TMAO did not show any associations. In women, L-carnitine was positively associated with max-IMT and PS. TMAO was correlated with both EPA and DHA levels, implying that fish is a major dietary source of TMAO in Japanese people. Our study found that plasma TMAO was not an apparent risk factor for atherosclerosis in elderly Japanese people, whereas a low level of TML might be a potential risk. L-carnitine may be a marker for atherosclerosis in women.

Reduced masticatory performance and not using dentures are associated with hypertension in older adults with tooth loss: the Shimane CoHRE study.

The relationship between masticatory performance and hypertension has seldom been studied. The association between hypertension and tooth loss with/without denture use is unclear. This cross-sectional study examined the relationship between hypertension and masticatory performance and whether the relationship between hypertension and the number of teeth varied with denture use among older Japanese adults. Hypertension was defined as a systolic or diastolic blood pressure ≥140 or ≥90 mm Hg, respectively, or the use of antihypertensive medications. Masticatory performance was assessed using a chewable gummy jelly. The number of teeth and denture use were visually assessed by a trained dental hygienist. Poisson regression analyses were carried out to estimate the prevalence ratio and 95% confidence interval (CI) of hypertension with the number of teeth (≥28, 20-27, or 0-19 teeth), quartiles of masticatory performance (Q1: highest [reference] to Q4: lowest), and tooth loss with/without denture use. Hypertension was significantly associated with masticatory performance in participants in Q3 (prevalence ratio = 1.35; 95% CI = 1.07, 1.72) and Q4 (prevalence ratio = 1.31; 95% CI = 1.01, 1.69). There was no association between tooth loss and hypertension. Compared to participants with >28 teeth, the prevalence ratios and 95% CIs of those without dentures and those with 20-27 teeth were 1.33 (95% CI = 1.06, 1.68) and 1.69 (95% CI = 1.21, 2.37), respectively, in those with 0-19 teeth. Masticatory performance was inversely associated with hypertension, and tooth loss without the use of dentures was related to hypertension. Therefore, masticatory function may be important for preventing hypertension among older adults.

Associations between physical frailty and living arrangements in Japanese older adults living in a rural remote island: The Shimane CoHRE study.

Background: Living arrangements have been known to be associated with physical frailty. However, the prevalence of frailty and its risk factors in remote islands is not understood. We examined the association between living arrangements and objectively measured frailty among older adults living in a remote island of Japan. Methods: Among older people living in Okinoshima, 656 older adults (75.6 ± 6.4 years) were analyzed. Physical frailty (robust, prefrailty, or frailty) was assessed using the 5-item frailty phenotype (unintentional weight loss, self-reported exhaustion, weakness, slow walking speed, and low physical activity). Physical functions (muscle mass, gait speed, and grip strength) were measured objectively. Results: The prevalence of frailty and prefrailty was 6.6% and 43.8%, respectively. Living with a spouse resulted in a significantly lower prevalence of frailty (p < 0.001) compared with other living arrangements. All objectively measured physical functions among those who lived with a spouse were significantly superior to those who lived with family or alone (p < 0.001). Multinomial logistic regression showed that living alone was significantly associated with frailty (odds ratio [OR] 2.36, 95% confidence interval [CI] 1.07-5.24) and prefrailty (OR 1.75, 95% CI 1.14-2.69) after adjusting for all covariates. Conclusion: The prevalence of frailty on remote islands seemed similar to that in urban areas. Older people living in remote islands might be able to maintain their physical health. Furthermore, living alone may correlate with increased risks of frailty and prefrailty. Among elderly individuals on remote islands, living with a spouse might be desirable to prevent (pre)frailty.

The Association Between Cyclooxygenase-2 -1195G/A (rs689466) Gene Polymorphism and the Clinicopathology of Lung Cancer in the Japanese Population: A Case-Controlled Study.

The single nucleotide polymorphisms of COX-2 gene, also known as PTGS2, which encodes a pro-inflammatory factor cyclooxygenase-2, alter the risk of developing multiple tumors, but these findings are not consistent for lung cancer. We previously reported that the homozygous COX-2 -1195A genotype is associated with an increased risk for chronic obstructive pulmonary disease (COPD) in Japanese individuals. COPD is a significant risk factor for lung cancer due to genetic susceptibility to cigarette smoke. In this study, we investigated the association between COX-2 -1195G/A polymorphism and lung cancer susceptibility in the Japanese population. We evaluated the genotype distribution of COX-2 -1195G/A using a polymerase chain reaction-restriction fragment length polymorphism assay for 330 newly diagnosed patients with lung cancer and 162 healthy controls. Our results show that no relationship exists between the COX-2 -1195G/A polymorphism and the risk of developing lung cancer. However, compared to the control group, the homozygous COX-2 -1195A genotype increased the risk for lung squamous cell carcinoma (odds ratio = 2.902; 95% confidence interval, 1.171-7.195; p = 0.021), whereas no association is observed with the risk for adenocarcinoma. In addition, Kaplan-Meier analysis shows that the genotype distribution of homozygous COX-2 -1195A does not correlate with the overall survival of patients with lung squamous cell carcinoma. Thus, we conclude that the homozygous COX-2 -1195A genotype confers an increased risk for lung squamous cell carcinoma in Japanese individuals and could be used as a predictive factor for early detection of lung squamous cell carcinoma.

Contribution of cystatin C gene polymorphisms to cerebral white matter lesions.

BACKGROUND: Vascular remodeling plays an important role in the development of arteriosclerosis and any of the resulting white matter lesions in the brain. An imbalance between cysteine proteases and the cysteine protease inhibitor cystatin C (CST3) may exacerbate vascular remodeling through degradation of extracellular matrix proteins. Therefore, we evaluated the association between functional polymorphisms in the CST3 gene and the development of cerebral white matter lesions. METHODS: In a total of 2,676 participants, 3 CST3 genepolymorphisms were genotyped in 92 cases with severe deep white matter hyperintensity (DWMH), and 184 subjects were randomly selected age- and sex-matched controls without any signs of DWMH. The genetic effects of these polymorphisms on DWMH and plasma CST3 levels were examined. CST3 expression vectors were transfected into an astrocytoma cell line and the expression level of CST3 mRNA was analyzed by quantitative RT-PCR. Intracellular and secreted levels of CST3 in the cell culture were quantified by Western blot and ELISA, respectively. RESULTS: A significant association was found between one CST3 gene haplotype and DWMH (p = 0.002). This haplotype was also associated with lower plasma CST3 levels (p = 0.01). An in vitro transfection study revealed that the +148A allele, which is included in the risk haplotype, significantly reduced the secretion and increased the intracellular accumulation of CST3; however, it had no effect on the mRNA expression. CONCLUSIONS: Our study shows that polymorphisms in the CST3 gene are significantly associated with the likelihood of DWMH. Substitution of A for G at +148 of the CST3 gene decreased the extracellular availability of CST3 in vitro, which might result in the activation of protease activity.

Association between hilliness and walking speed in community-dwelling older Japanese adults: A cross-sectional study.

PURPOSE: This cross-sectional study investigated the association between hilliness and walking speed in community-dwelling older adults, and whether it varied according to their car-driving status. METHODS: Data were collected from 590 participants aged 65 and older living in Okinoshima Town, Shimane prefecture, Japan, in 2018. Comfortable walking speed (m/s) was objectively assessed. Hilliness was measured by the mean land slope (degree) within a 500-m or 1000-m network buffer around each participant's home using a geographic information system. A multiple linear regression examined whether the land slope was associated with walking speed, adjusted for sex, age, body mass index, smoking habits, alcohol consumption habits, exercise habits, chronic disease, and living arrangements. A stratified analysis by car-driving status was also conducted. RESULTS: After adjusting for all confounders, the land slope within the 500-m or 1000-m network buffer was negatively associated with walking speed (B = -0.007, 95% CI [-0.011, -0.002]; B = -0.007, 95% CI [-0.011, -0.003], respectively). The stratified analysis by car-driving status showed that living in a hilly area was negatively associated with walking speed among non-drivers in the 500-m or 1000-m network buffer (B = -0.011, 95% CI [-0.017, -0.004]; B = -0.012, 95% CI [-0.019, -0.006]), though there were no associations among drivers. CONCLUSIONS: A hilly environment is positively associated with slow walking speed in community-dwelling older adults in Japan. Moreover, car-driving status potentially modifies the relationship between living in a hilly environment and slow walking speed.

An association analysis between hypertension, dementia, and depression and the phases of pre-sarcopenia to sarcopenia: A cross-sectional analysis.

Sarcopenia is intricately related to aging associated diseases, such as neuropsychiatric disorders, oral status, and chronic diseases. Dementia and depression are interconnected and also related to sarcopenia. The preliminary shift from robust to sarcopenia (i.e., pre-sarcopenia) is an important albeit underdiscussed stage and is the focus of this study. Identifying factors associated with pre-sarcopenia may lead to sarcopenia prevention. To separately examine the effects of dementia and depression on pre-sarcopenia/sarcopenia, we conducted multiple analyses. This cross-sectional study used health checkup data from a rural Japanese island. The participants were aged 60 years and above, and the data included muscle mass, gait speed, handgrip strength, oral status (teeth and denture), chronic diseases (e.g., hypertension), dementia (cognitive assessment for dementia, iPad Version), and depression (self-rating depression scale). A total of 753 older adult participants were divided into the sarcopenia (n = 30), pre-sarcopenia (n = 125), and robust (n = 598) groups. An ordered logit regression analysis indicated that age and depression were positively correlated with sarcopenia, while hypertension was negatively associated with it. A multiple logistic regression analysis between the robust and pre-sarcopenia groups showed significant associations between the same three variables. Depression was associated with pre-sarcopenia, but not dementia. There was also a significant association between hypertension and pre-sarcopenia. Further research is needed to reveal whether the management of these factors can prevent sarcopenia.