Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

Background/Aims: We aimed to determine whether the concentration of serum C-reactive protein (CRP) is associated with cognitive function in an adult Japanese population. Methods: Participants of this cross-sectional study were from a subgroup of the Project in Sado for Total Health (PROST
n = 454
mean age, 70.5 years). The cognitive state was evaluated using the Mini-Mental State Examination (MMSE), and those with an MMSE score &lt
24 were considered 'cognitively declined'. Concentrations of serum high-sensitivity CRP were measured. Multiple logistic regression analysis was used to calculate odds ratios (ORs) for cognitive decline, adjusting for the covariates of age, sex, BMI, disease history, and APOE allele. Results: Of the 454 participants, 94 (20.7%) were cognitively declined. Relative to the lowest (first) quartile of CRP concentration, adjusted ORs were 1.29 (95% CI 0.61-2.75) for the second, 1.78 (95% CI 0.82-3.86) for the third, and 3.05 (95% CI 1.45-6.42) for the highest (fourth) quartiles (p for trend = 0.018). When data were stratified by sex, the association between CRP concentration and cognitive decline was observed only in women. Conclusion: Our findings suggest an association between higher CRP concentration and lower cognitive function. Chronic inflammation may affect cognitive function in adults, in particular women.

DOI： 10.1159/000442585

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Background: Roles of the syntaxin-1ACaMKII interaction are not physiologically understood in vivo.Results: A point mutation in syntaxin-1A caused abnormal plasticity, recycling, and behaviors in mice. Conclusion: The CaMKII/syntaxin-1A interaction is essential for maintenance of neuronal plasticity. Significance: Syntaxin-1A is involved in regulatory pathways in higher brain functions.
Syntaxin-1A is a t-SNARE that is involved in vesicle docking and vesicle fusion; it is important in presynaptic exocytosis in neurons because it interacts with many regulatory proteins. Previously, we found the following: 1) that autophosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII), an important modulator of neural plasticity, interacts with syntaxin-1A to regulate exocytosis, and 2) that a syntaxin missense mutation (R151G) attenuated this interaction. To determine more precisely the physiological importance of this interaction between CaMKII and syntaxin, we generated mice with a knock-in (KI) syntaxin-1A (R151G) mutation. Complexin is a molecular clamp involved in exocytosis, and in the KI mice, recruitment of complexin to the SNARE complex was reduced because of an abnormal CaMKII/syntaxin interaction. Nevertheless, SNARE complex formation was not inhibited, and consequently, basal neurotransmission was normal. However, the KI mice did exhibit more enhanced presynaptic plasticity than wild-type littermates; this enhanced plasticity could be associated with synaptic response than did wild-type littermates; this pronounced response included several behavioral abnormalities. Notably, the R151G phenotypes were generally similar to previously reported CaMKII mutant phenotypes. Additionally, synaptic recycling in these KI mice was delayed, and the density of synaptic vesicles was reduced. Taken together, our results indicated that this single point mutation in syntaxin-1A causes abnormal regulation of neuronal plasticity and vesicle recycling and that the affected syntaxin-1A/CaMKII interaction is essential for normal brain and synaptic functions in vivo.

DOI： 10.1074/jbc.M113.504050

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OBJECTIVE: To determine the longitudinal association between chronic pain in the lower extremities and low back and the odds of recurrent falls in middle-aged and older people. DESIGN: A cohort study. SETTING: Communities in Japan. PARTICIPANTS: Participants were 7540 community-dwelling volunteers aged 40-74 years (N=7540). The baseline survey was a self-administered questionnaire conducted between 2011-2013. Predictors were presence of chronic pain in the knee, foot or ankle, and low back, with the degree of pain categorized as none, very mild/mild, moderate, or severe/very severe. Covariates in the multivariate model of chronic pain in a site were demographics, body mass index, physical activity level, disease history, and chronic pain in the other 2 sites. Logistic regression analysis was used to calculate odds ratios (ORs). INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Recurrent falls in the year before the 5-year follow-up survey. RESULTS: Mean participant age was 60.2 years. Higher degrees of chronic pain were associated with higher odds of recurrent falls for the knee (P=.0002) with a higher OR of 1.48 (95% CI: 1.11-1.97), for the foot or ankle (P=.0001) with a higher OR of 1.97 (95% CI: 1.36-2.86), and for the low back (P=.0470) with a higher OR of 1.45 (95% CI: 1.09-1.91) in those with any degree of pain relative to those without pain. Higher degrees of chronic knee pain were associated with higher odds of recurrent falls in women (P=.0005), but not in men (P=.0813). Meanwhile, higher degrees of chronic low back pain were associated with the odds of recurrent falls in men (P=.0065), but not in women (P=.8735). CONCLUSIONS: Chronic pain in the knee, foot or ankle, and lower back was independently and dose-dependently associated with a higher risk of recurrent falls. A marked sex-dependent difference was also noted in the association.

DOI： 10.1016/j.apmr.2023.09.021

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

INTRODUCTION: The association between body size and fracture risk is complex and varies by sex and ethnicity. This study aimed to examine associations of body mass index (BMI) and height with osteoporotic fracture risk in middle-aged and older people. MATERIALS AND METHODS: This 10-year cohort study included 13,151 community-dwelling Japanese people aged 40-74 years. A self-administered questionnaire survey was conducted at baseline to obtain information on demographic characteristics, body size, lifestyle, and disease history. BMI (kg/m2) was categorized as underweight (< 18.5), low-normal (18.5-21.7), high-normal (21.8-24.9), overweight (25.0-29.9), and obese (≥ 30.0). Height was categorized into quartiles. All incident cases of major osteoporotic fractures, including fractures of the distal radius, neck of the humerus, neck or trochanter of the femur, and vertebrae, were obtained from medical records during follow-up. RESULTS: Mean participant age was 58.8 years. In men, the underweight group had a significantly higher hazard ratio (HR) for total fracture (adjusted HR = 2.46), and the obese group had significantly higher HRs for total (adjusted HR = 3.01) and vertebral (HR = 3.77) fractures relative to the reference (overweight) group. No significant associations were observed between BMI and risk of any fracture in women. Higher quartiles of height were associated with higher vertebral fracture risk (adjusted P for trend = 0.023) only in women. CONCLUSION: BMI and osteoporotic fracture risk showed a U-shaped association in men, whereas higher height was associated with higher vertebral fracture risk in women, suggesting sex-dependent differences in these associations.

DOI： 10.1007/s00774-023-01478-z

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Other Link： https://link.springer.com/article/10.1007/s00774-023-01478-z/fulltext.html

Authorship：Lead author,　Corresponding author  

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Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese  

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OBJECTIVE: Alcohol drinking and tobacco smoking have impacts on lifestyle-related diseases, but their association with dementia remains a debated topic. This study aimed to examine longitudinal associations between alcohol consumption, smoking, and dementia risk in middle-aged and older Japanese people. METHODS: This study used a cohort design with an 8-year follow-up. Participants were community-dwelling Japanese people (N = 13,802) aged 40-74 years. The baseline survey, including a self-administered questionnaire, was conducted in 2011-2013. Predictors were alcohol consumption and tobacco smoking. The outcome was incident dementia obtained from a long-term care insurance database. Covariates were demographics, lifestyle factors, body mass index, general health status, and history of stroke, diabetes, and depression. RESULTS: Participant mean age was 59.0 years. The 1-149, 150-299, and 300-449 g ethanol/week groups had significantly lower adjusted hazard ratios (HRs) (0.62, 0.59, and 0.47, respectively) compared with the reference group, with no significant linear association. HRs increased toward 1 when past-drinkers and those with poor health status and a disease history were excluded (0.80, 0.66, and 0.82, respectively). Higher smoking levels were dose-dependently associated with a higher HR (adjusted P for trend = 0.0105), with the ≥20 cigarettes/day group having a significantly higher adjusted HR (1.80). Heavy drinkers (≥449 g ethanol/week) with smoking habits, but not those without smoking habits, had higher dementia risk (P for interaction = 0.0046). CONCLUSION: Light-to-moderate alcohol consumption is associated with decreased dementia risk, and smoking is dose-dependently associated with increased dementia risk, with an interaction between high alcohol consumption and smoking on dementia risk.

DOI： 10.1016/j.maturitas.2023.107788

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BACKGROUND: The association between body mass index (BMI) and dementia risk is heterogeneous across age groups and might be influenced by sex. OBJECTIVE: This study aimed to clarify sex differences in the association between BMI and dementia risk in community-dwelling people. METHODS: This cohort study with an 8-year follow-up targeted 13,802 participants aged 40-74 years at baseline in 2011-2013. A self-administered questionnaire requested information on body size, including height, weight, and waist circumference (the values of which were validated by direct measurement), socio-demographics, lifestyle, and disease history. BMI was calculated and categorized as < 18.5 (underweight), 18.5-20.6 (low-normal), 20.7-22.7 (mid-normal), 22.8-24.9 (high-normal), 25.0-24.9 (overweight), and≥30.0 kg/m2 (obese). Incident cases of dementia were obtained from the long-term care insurance database. A Cox proportional hazards model was used to calculate multivariable-adjusted hazard ratios (HRs). RESULTS: The mean age of participants was 59.0 years. In men, higher BMI was associated with lower dementia risk (fully-adjusted p for trend = 0.0086). In women, the association between BMI and dementia risk was U-shaped; the "underweight," "low-normal," and "overweight" groups had a significantly higher risk (fully-adjusted HR = 2.12, 2.08, and 1.78, respectively) than the reference ("high-normal" group). These findings did not change after excluding dementia cases which occurred within the first four years of the follow-up period. CONCLUSION: Overweight/obese women, but not men, had an increased risk of dementia, suggesting that sex differences in adiposity might be involved in the development of dementia.

DOI： 10.3233/JAD-230294

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BACKGROUND: Association between vitamin D levels and the occurrence of depression are not always consistent. The present cohort study aimed to determine this association in older adults, using a method for measuring vitamin D levels which is more accurate than those used in previous studies. METHODS: Participants were 3447 individuals aged 40-74 years without depressive symptoms at baseline who participated in the 5-year follow-up survey. The baseline investigation, including a self-administered questionnaire survey and blood collection, was conducted in 2011-2013. Plasma 25-hydroxyvitamin D (25[OH]D) levels were measured, and divided into overall quartiles summed up by sub-quartiles and stratified by age, sex, and season. The outcome was depressive symptoms determined by the CES-D (11-item, cut-off score of 6/7) 5 years later. Covariates were demographics, lifestyles, baseline CES-D score, and disease history. RESULTS: Mean plasma 25(OH)D levels were 58.0 nmol/L in men and 45.7 in women (P < 0.0001), and cumulative incidences of depressive symptoms were 249/1577 (15.8 %) in men and 313/1870 (16.7 %) in women (P = 0.4526). The lower 25(OH)D quartile group had higher adjusted ORs in men and women combined (P for trend = 0.0107) and women (P for trend = 0.0003), but not in men. Adjusted ORs of the lowest quartile group were significantly higher than the highest group in men and women combined (OR = 1.39, 95 % CI: 1.06-1.81) and women (OR = 1.89, 95 % CI: 1.31-2.72). LIMITATION: Depressive symptoms were self-reported. CONCLUSIONS: Low vitamin D levels were associated with a high risk of depressive symptoms, especially in women. Women are thus considered a major target for preventing vitamin D deficiency to address depression.

DOI： 10.1016/j.jad.2022.12.104

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DOI： 10.1186/s11556-022-00306-z

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BACKGROUND: Falls are important causes of injury and mortality in older people, and associated medical costs can be enormous. Physical activity (PA) is a potential preventive factor for falls. However, few studies have examined the effect of different types of PA on fall prevention. This study aimed to evaluate the association between PA levels and the incidence of recurrent falls by type of PA in middle-aged and older people. METHODS: This cohort study targeted 7,561 community-dwelling individuals aged 40-74 years who did not experience recurrent falls in the year before baseline. Information on PA levels, demographics, body size, lifestyle, and fall/disease history was obtained using a self-administered questionnaire in the baseline survey. Levels of total PA, leisure-time PA, and non-leisure-time PA (occupation, commuting, and housework) were estimated using metabolic equivalent (MET) scores (MET-h/day; hours spent on a given activity per day multiplied by its MET intensity). PA levels were categorized into four groups. Falls were recorded as none, once, or twice or more (recurrent falls). The outcome of the study was the incidence of recurrent falls in the past year before a survey conducted 5 years after the baseline survey. Logistic regression analyses were performed to calculate odds ratios for recurrent falls. RESULTS: Higher total PA and non-leisure-time PA levels were associated with a higher risk of recurrent falls (P for trend = 0.0002 and 0.0001, respectively), with the highest total PA and non-leisure-time PA groups having a significantly higher adjusted OR (1.96 [95%CI:1.33-2.88] and 2.15 [95%CI:1.48-3.14], respectively) relative to the lowest group (reference). As for leisure-time PA, the medium group had a significantly lower adjusted OR (0.70 [95%CI:0.49-0.99]) relative to the reference group. By sex, the adjusted OR in the medium leisure-time PA group was significantly lower relative to the reference group in women (0.50 [95%CI: 0.29-0.85]) but not in men. CONCLUSIONS: Medium level leisure-time PA reduces the risk of recurrent falls in middle-aged and older people, whereas higher level non-leisure-time PA is associated with a higher risk of recurrent falls.

DOI： 10.1186/s11556-022-00300-5

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OBJECTIVE: Although physical activity (PA) in late life is considered a preventive factor for dementia, effects of different types of PAs on the development of dementia in early old age are unclear. This study aimed to determine the effect of leisure-time and non-leisure-time PAs on dementia risk in middle-aged and older adults during an 8-year follow-up. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: Participants were 13,773 community-dwelling individuals aged 40-74 years who completed the baseline self-administered questionnaire survey of the Murakami cohort study in 2011-2013. METHODS: Main predictors were leisure-time and non-leisure-time (commute, occupational work, and housework) PAs as assessed by MET score (MET-hour/d). The outcome was newly developed dementia determined using a long-term care insurance database. Covariates included demographics, lifestyle, body size, disease history, and PA level. Hazard ratios (HRs) were calculated using Cox proportional hazards models. RESULTS: Mean age of participants was 59.0 (SD 9.3) years. Higher levels of leisure-time PA were associated with lower HRs (adjusted P for trend <.001), with all tertiles having significantly lower HRs (low: 0.71, 95% CI 0.51-0.99; medium: 0.59, 95% CI 0.43-0.81; high: 0.55, 95% CI 0.41-0.75) relative to the reference (zero). Higher quartiles of non-leisure-time PA were associated with lower adjusted HRs for dementia (adjusted P for trend < .001), with the second-fourth quartiles having significantly lower HRs (second: 0.73, 95% CI 0.54-0.98; third: 0.59, 95% CI 0.43-0.81; fourth: 0.55, 95% CI 0.41-0.75) relative to the lowest quartile. These associations were robust regardless of sex and age group. CONCLUSIONS AND IMPLICATIONS: Both leisure-time and non-leisure-time PAs are independently and robustly associated with a reduced risk of dementia.

DOI： 10.1016/j.jamda.2022.01.053

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Several studies have reported an association between sarcopenia and depression. Their results, however, are inconsistent, partly due to small sample sizes and lack of consideration of important confounders. The present study aimed to cross-sectionally examine this association in community-dwelling people in Japan. This study used baseline data from the Yuzawa cohort study (age ≥ 40 years), with the final analysis population comprising 2,466 participants. A self-administered questionnaire was used to elicit information related to sarcopenia, depressive symptoms, demographic characteristics, anthropometrics, disease history, and lifestyles. Sarcopenia was diagnosed using SARC-F, a validated questionnaire including components of Strength, Assistance in walking, Rising from a chair, Climbing stairs, and Falls. Depressive symptoms were assessed using the 11-item version of the Center for Epidemiologic Studies Depression Scale (CES-D). For depressive symptoms, prevalence ratios (PRs) were calculated, and odds ratio (ORs) were obtained using simple and multiple logistic regression analyses. Mean age of participants was 61.7 years (standard deviation = 11.8), and 10.5% and 34.7% had sarcopenia and depressive symptoms, respectively. Sarcopenic individuals had a significantly higher PR (2.00), unadjusted OR (3.67), and adjusted OR (4.96) compared to non-sarcopenic individuals, with an estimated adjusted PR of 2.7. There was a significant dose-dependent association between SARC-F scores and depressive symptoms in sarcopenic individuals (adjusted P for trend = 0.0028). In conclusion, sarcopenia and depressive symptoms were robustly associated in community-dwelling, middle-aged and older people in Japan. However, the direction of this association is unclear, and a future cohort study will be needed to determine causality.

DOI： 10.1620/tjem.2022.J024

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INTRODUCTION: Secular changes in hip fracture incidence have been reported in the last few decades in Japan, but whether long-term bone mineral density (BMD) is also changing is unclear. This study aimed to determine whether BMD of Japanese women has changed over time. METHODS: Subjects were 10,649 adult women who underwent BMD measurement in a health check-up population in Niigata, Japan, between 1995 and 2013. BMD of the distal, non-dominant forearm was measured by dual-energy X-ray absorptiometry. Demographic information and BMI were also obtained. Secular trends were determined by linear regression analysis. RESULTS: BMD of subjects in their 40's decreased significantly in the age-adjusted model (P for trend=0.0162), but not in the age- and BMI-adjusted model (P for trend=0.2171). BMD of subjects in their 50's decreased marginally in the age-adjusted model (P for trend=0.0535), but not in the age- and BMI-adjusted model (P for trend=0.6601). BMDs of subjects in their 30's and 60's did not significantly change, while BMIs of subjects in their 40's-60's decreased significantly. CONCLUSIONS: A secular decrease in BMD, partly attributed to decreases in BMI, was observed in middle-aged Japanese women from 1995 to 2013. Measures to help maintain suitable BMI will be necessary to prevent a decrease in BMD among women.

DOI： 10.5387/fms.2021-10

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OBJECTIVES: A positive association between levels of blood 25-hydroxyvitamin D (25[OH]D), an index of vitamin D status, and physical balance has been reported from cross-sectional studies, but longitudinal studies are rare. The present study aimed to test the hypothesis that low serum 25(OH)D levels are longitudinally associated with impaired postural sway over a 6-year follow-up period in older women. METHODS: The present cohort consisted of 392 community-dwelling Japanese women aged ≥69 years. Baseline examinations included serum 25(OH)D and physical performance tests, including postural sway velocity. Standing postural sway was evaluated by measuring gravity-center sway velocity. Follow-up physical performance tests were conducted 6 years later. RESULTS: Mean subject age and serum 25(OH)D levels were 73.3 years (SD 3.7) and 61.0 nmol/L (SD 16.9), respectively. No significant association was found between 25(OH)D levels and changes in postural sway velocity (adjusted P for trend=0.72). Women with 25(OH)D <30 nmol/L tended to have lower Δpostural sway velocity than those with 25(OH)D ≥30 nmol/L (mean, -0.59 vs 0.37 cm/s, respectively; adjusted P=0.13). CONCLUSIONS: Vitamin D levels are not longitudinally associated with impaired postural sway in older women. Further longitudinal studies are needed to corroborate the results of this study.

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Language：Japanese   Publisher：新潟医学会  

著者らは、村上コホート研究のベースライン調査と5年後フォローアップ調査において、自記式の調査票により、生活習慣、病歴などの情報を得た。この縦断データを利用し、中高年の喫煙、飲酒、運動の習慣の5年間の変化と、禁煙、節酒、運動の習慣の獲得に関わる要因について検討した。対象者は5年後フォローアップ調査に参加した8,487人で、ベースライン調査時の年齢は40から74歳であった。ベースライン調査票の利用項目は、性、年齢、婚姻歴、学歴、職業、現在の健康状態、病歴(がん、心筋梗塞、脳卒中、糖尿病)、現在の喫煙の有無、飲酒頻度、余暇での運動の頻度、肥満度(Body mass index)であった。5年後フォローアップ調査票の利用項目は、現在の喫煙の有無、飲酒頻度、余暇での運動の頻度であり、これらの項目をベースライン時と5年後で比較した。また、ベースライン時に喫煙者、毎日の飲酒者、または余暇での運動の習慣のない人(<1回/週)について、5年後にこれらの習慣がよい方向に変化した人、すなわち禁煙、毎日の飲酒中止、週に1回以上の運動開始した人のベースライン時の要因(予測要因)を解析した。ベースラインと5年後の比較では、喫煙と飲酒については全体的に禁煙・節酒の方向に変化する傾向が見られたものの、運動の習慣については明確な変化が見られなかった。好ましくない喫煙、飲酒、運動の習慣を持つ人の生活習慣改善に関わる要因を解析した結果、いずれの習慣も高齢であるほど改善する傾向が見られた。飲酒習慣の変化には体調不良の関与が、運動の習慣の獲得には教育の重要性が示唆されたが、禁煙に関しては加齢以外の関連要因を見いだせなかった。今後の慢性疾患の予防対策にこれらの情報が活用されることを期待する。(著者抄録)

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J00990&link_issn=&doc_id=20220705060001&doc_link_id=http%3A%2F%2Fhdl.handle.net%2F10191%2F0002000703&url=http%3A%2F%2Fhdl.handle.net%2F10191%2F0002000703&type=%90V%8A%83%91%E5%8Aw%81F%90V%8A%83%91%E5%8Aw%8Aw%8Fp%83%8A%83%7C%83W%83g%83%8A_Nuar&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F80230_3.gif

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BACKGROUND: Income inequality has dramatically increased worldwide, and there is a need to re-evaluate the association between socio-economic status (SES) and depression. Relative contributions of household income and education to depression, as well as their interactions, have not been fully evaluated. This study aimed to examine the association between SES and depressive symptoms in Japanese adults, focusing on interactions between education and household income levels. METHODS: This cross-sectional study used data from baseline surveys of two cohort studies. Participants were 38,499 community-dwelling people aged 40-74 years who participated in baseline surveys of the Murakami cohort study (2011-2012) and Uonuma cohort study (2012-2015) conducted in Niigata Prefecture, Japan. Information regarding marital status, education level, household income, occupation, activities of daily living (ADL), and history of cancer, myocardial infarction, stroke, and diabetes was obtained using a self-administered questionnaire. Depressive symptoms were examined using the Center for Epidemiologic Studies Depression Scale (CES-D). Logistic regression analysis was used to obtain odds ratios (ORs). Covariates included age, sex, marital status, education, household income, occupation, ADL, and disease history. RESULTS: Individuals with higher education levels had lower ORs (adjusted P for trend = 0.0007) for depressive symptoms, independently of household income level. The OR of the university-or-higher group was significantly lower than that of the junior high school group (adjusted OR = 0.79). Individuals with lower household income levels had higher ORs (adjusted P for trend< 0.0001) for depressive symptoms, independently of education level. The type of occupation was not associated with depressive symptoms. In subgroup analyses according to household income level, individuals with higher education levels had significantly lower ORs in the lowest- and lower-income groups (adjusted P for trend = 0.0275 and 0.0123, respectively), but not in higher- and highest-income groups (0.5214 and 0.0915, respectively). CONCLUSIONS: Both education and household income levels are independently associated with the prevalence of depressive symptoms, with household income levels showing a more robust association with depressive symptoms than education levels. This suggests that a high household income level may offset the risk of depressive symptoms from having a low education level.

DOI： 10.1186/s12889-021-12168-8

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OBJECTIVES: Coffee, green tea, and caffeine are potential preventive factors for dementia, but the underlying evidence is insufficient. This study aimed to examine associations between the consumption of coffee, green tea, and caffeine and dementia risk in middle-aged and older people. METHODS: This was a cohort study with an 8.0-year follow-up. Participants were community-dwelling individuals (n = 13,757) aged 40-74 years. A self-administered questionnaire survey was conducted in 2011-2013. Predictors were the consumption of coffee/green tea, from which caffeine consumption was estimated. The outcome was incident dementia obtained from the long-term care insurance database. Covariates were demographic factors, body mass index, physical activity, energy, smoking, drinking, and disease history. Adjusted hazard ratios (HRs) were calculated using Cox proportional hazards models. HRs were also calculated using a Cox model with delayed entry. RESULTS: The number of dementia cases during the study period was 309. Participants with higher coffee consumption had lower HRs (adjusted p for trend = 0.0014), with the fifth quintile (≥326 ml/day) having a significantly lower HR (0.49, 95% confidence interval [CI]: 0.30-0.79) than the first quintile (<26 ml/day, reference). Similarly, participants with higher caffeine consumption had a significantly lower HR (adjusted p for trend = 0.0004) than the reference. The Cox model with delayed entry yielded similar results. These associations were significant in men, but not in women. Moreover, participants who consumed 2-2.9 cups/day and ≥3 cups/day of coffee had lower HRs (0.69, 95% CI: 0.48-0.98 and 0.53, 95% CI: 0.31-0.89, respectively) than those who consumed 0 cup/day. The association between green tea consumption and reduced dementia risk was significant (adjusted p for trend = 0.0146) only in the 60-69 years age subgroup. CONCLUSIONS: High levels of coffee and caffeine consumption were significantly associated with a reduced dementia risk in a dose-dependent manner, especially in men. Moreover, coffee consumption of ≥3 cups/day was associated with a 50% reduction in dementia risk.

DOI： 10.1111/jgs.17407

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AIM: Although menstrual/reproductive factors are known to be associated with physical disability, little is known about these associations in relation to activities of daily living (ADL). This study aimed to clarify associations between menstrual/reproductive factors and ADL limitations in peri- and postmenopausal women. STUDY DESIGN: A nested case-control study of the Japan Public Health Center-based Prospective (JPHC) Study. METHODS: The main outcome measure was self-reported ADL levels in the 10-year follow-up questionnaire survey of the JPHC Study conducted between 2000 and 2004 (N = 36 460). Women who "live inside almost independently, but go out with assistance" or had a lower level of activity were considered to have ADL limitations ("cases"), and all others served as controls. Candidate menstrual/reproductive predictors were as follows: menarcheal age, menopausal status, menopausal age, regularity of menses, menstrual cycle, number of pregnancies, age at first pregnancy, number of deliveries, age at first delivery, and breast feeding. Multiple logistic regression analyses were conducted, and odds ratios adjusted for age and past lifestyle were calculated. RESULTS: Mean ages of cases (N = 592) and controls (N = 38 656) were 68.3 (SD = 7.6) and 61.1 (SD = 7.7) years, respectively. With respect to menopausal age, groups aged <45 and ≥55 years had significantly higher adjusted ORs (1.44, 95% CI: 1.09-1.90 and 1.55, 95%CI: 1.09-2.18, respectively) than the reference group (50-54 years). Multiparous women had significantly lower ORs than nulliparous women. CONCLUSION: Our findings suggest that menopausal age and parity may predict future ADL limitations in women.

DOI： 10.1111/jog.14959

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BACKGROUND: Beneficial effects of napping on cognition have been suggested in cross-sectional studies. This study aimed to clarify longitudinal associations between cognitive decline and sleep characteristics, particularly daytime napping, over a 5-year period in older adults. METHODS: Study participants were 389 community-dwelling individuals aged ≥65 years living in Ojiya City, Niigata, Japan. Baseline and follow-up examinations were conducted in 2011-2013 and 2016-2018, respectively. Trained nurses visited and interviewed participants to collect the following information at baseline and follow-up: demographic characteristics, disease history, lifestyle habits including bedtime, sleeping hours, and daytime nap duration, and cognitive function. The assessment of cognitive function was performed using the revised Hasegawa's dementia scale (HDS-R), with cognitive decline defined as a change in the HDS-R of ≤ - 3 over 5 years. Odds ratios (ORs) for cognitive decline were calculated using multiple logistic regression analysis. RESULTS: Mean age of participants was 74.6 years (SD 6.4), and the cumulative incidence of cognitive decline was 106/389 (27.3%). The adjusted OR for 1-29 min daytime napping was significantly lower compared to that for no napping (OR = 0.47, 95%CI: 0.23-0.96). Earlier bedtime was associated with cognitive decline (adjusted P for trend = 0.0480). CONCLUSION: Short daytime napping (< 30 min) reduces the risk of cognitive decline over 5 years for community-dwelling older people. A future study will be necessary to confirm the effect of short napping on the reduction of risk for clinically diagnosed dementia.

DOI： 10.1186/s12877-021-02418-0

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

AIMS: A prior meta-analysis found that obesity (body mass index [BMI] ≥ 30 kg/m2 ) was associated with a high fall risk, while being overweight (BMI≥25, <30 kg/m2 ) was associated with the lowest fall risk. However, whether these associations hold true for East Asians is unknown. This study aimed to assess the association between BMI and incidence of recurrent falls in Japanese aged 40-74 years. METHODS: This 5-year follow-up cohort study involved 7538 community-dwelling individuals who did not experience recurrent falls in the year before the baseline study. Information on demographics, body size, lifestyle, and disease history was obtained using a self-administered questionnaire. BMI was categorized as <18.5 (underweight), 18.5-20.6 (low-normal), 20.7-22.7 (mid-normal, reference), 22.8-24.9 (high-normal), and ≥ 25.0 kg/m2 (overweight). The outcome was recurrent falls reported, and fall history in the previous year was recorded as none, once, or twice or more (recurrent falls). RESULTS: Mean BMI was 23.5 kg/m2 (SD 2.9) for men and 22.7 kg/m2 (SD 3.2) for women. The adjusted odds ratio (OR) for recurrent falls in the BMI ≥25 group was significantly higher (1.41, 95%CI: 1.02-1.93) than that in the reference group. The adjusted OR in the BMI ≥25 group was significantly higher than that in the reference group for the age ≥ 60 subgroup (1.62, 95%CI: 1.09-2.40), but not for the age < 60 subgroup (OR = 1.04, 95%CI: 0.60-1.80). CONCLUSIONS: Being overweight may be a risk factor for recurrent falls in community-dwelling older Japanese. Further studies are needed to determine the underlying mechanism. Geriatr Gerontol Int 2021; 21: 498-505.

DOI： 10.1111/ggi.14167

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/ggi.14167

Language：English   Publishing type：Research paper (scientific journal)  

Although dietary Ca, vitamin D and vitamin K are nutritional factors associated with osteoporosis, little is known about their effects on incident osteoporotic fractures in East Asian populations. This study aimed to determine whether intakes of these nutrients predict incident osteoporotic fractures. We adopted a cohort study design with a 5-year follow-up. Subjects were 12 794 community-dwelling individuals (6301 men and 6493 women) aged 40-74 years. Dietary intakes of Ca, vitamin D and vitamin K were assessed with a validated FFQ. Covariates were demographic and lifestyle factors. All incident cases of major osteoporotic limb fractures, including those of the distal forearm, neck of humerus, neck or trochanter of femur and lumbar or thoracic spine were collected. Hazard ratios (HR) for energy-adjusted Ca, vitamin D and vitamin K were calculated with the residual method. Mean age was 58·8 (sd 9·3) years. Lower energy-adjusted intakes of Ca and vitamin K in women were associated with higher adjusted HR of total fractures (Pfor trend = 0·005 and 0·08, respectively). When vertebral fracture was the outcome, Pfor trend values for Ca and vitamin K were 0·03 and 0·006, respectively, and HR of the lowest and highest (reference) intake groups were 2·03 (95 % CI 1·08, 3·82) and 2·26 (95 % CI 1·19, 4·26), respectively. In men, there were null associations between incident fractures and each of the three nutrient intakes. Lower intakes of dietary Ca and vitamin K were independent lifestyle-related risk factors for osteoporotic fracture in women but not men. These associations were robust for vertebral fractures, but not for limb fractures.

DOI： 10.1017/S0007114520001567

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Little is known about predictors of decline in vitamin D status (vitamin D decline) over time. We aimed to determine demographic and lifestyle variables associated with vitamin D decline by sufficiently controlling for seasonal effects of vitamin D uptake in a middle-aged to elderly population. Using a longitudinal study design within the larger framework of the Murakami Cohort Study, we examined 1044 individuals aged between 40 and 74 years, who provided blood samples at baseline and at 5-year follow-up, the latter of which were taken on a date near the baseline examination (±14 d). Blood 25-hydroxyvitamin D (25(OH)D) concentrations were determined with the Liaison® 25OH Vitamin D Total Assay. A self-administered questionnaire collected demographic, body size and lifestyle information. Vitamin D decline was defined as the lowest tertile of 5-year changes in blood 25(OH)D (Δ25(OH)D) concentration (<6·7 nmol/l). Proportions of those with vitamin D decline were 182/438 (41·6 %) in men and 166/606 (27·4 %) in women (P < 0·0001). In men, risk of vitamin D decline was significantly lower in those with an outdoor occupation (P = 0·0099) and those with the highest quartile of metabolic equivalent score (OR 0·34; 95 % CI 0·14, 0·83), and higher in those with 'university or higher' levels of education (OR 2·92; 95 % CI 1·04, 8·19). In women, risk of vitamin D decline tended to be lower with higher levels of vitamin D intake (Pfor trend = 0·0651) and green tea consumption (Pfor trend = 0·0025). Predictors of vitamin D decline differ by sex, suggesting that a sex-dependent intervention may help to maintain long-term vitamin D levels.

DOI： 10.1017/S0007114520001580

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Specific components of physical activity, such as vigorous exercise and heavy occupational work, are known to increase the risk of chronic low back pain (CLBP) and chronic knee pain (CKP), but impacts of other components are less known. This study aimed to assess the relationship between total physical activity and risk of CLBP and CKP from a public health perspective. METHODS: Participants were 7,565 individuals, aged 40-74 years, who did not have CLBP or CKP, and who participated in the 5-year follow-up survey. A self-administered questionnaire was used to obtain information on demographics, body size and lifestyle (including physical activity) in the baseline survey in 2011-2013, and on CLBP and CKP using Short Form 36 (SF-36) in the follow-up survey. Sitting, standing, walking and strenuous work for occupational activity were assessed for total physical activity, and walking slowly, walking quickly, light to moderate exercise and strenuous exercise were assessed for leisure-time physical activity using metabolic equivalent hours/day (METs score). RESULTS: Mean age of participants was 60.1 years (SD, 8.8). Participants with higher METs scores had a significantly higher risk of CKP (p for trend = 0.0089, OR of 4th quartile = 1.29, 95% CI: 1.04-1.59 vs. 1st quartile), but not CLBP. An intermediate leisure-time METs score was associated with a lower risk of CLBP (OR = 0.75, 95%CI: 0.61-0.92 vs. 0 METs-group). CONCLUSIONS: A high level of total physical activity may increase the risk of CKP, whereas an intermediate level of leisure-time physical activity may decrease the risk of CLBP, in middle-aged and elderly individuals. SIGNIFICANCE: Evidence on the longitudinal association between total physical activity and CLBP and CKP in middle-aged and elderly people is lacking. We conducted a cohort study to assess this association, and found that high levels of total physical activity increased risk of CKP, and intermediate levels of leisure-time physical activity decreased risk of CLBP. This suggests that the effect of physical activity on chronic pain differed by pain site.

DOI： 10.1002/ejp.1535

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Language：English   Publishing type：Research paper (scientific journal)  

Positive associations between vitamin D levels and hand grip strength have been reported worldwide, but the results are not consistent and few studies on East Asian populations have been published. The aim of this study was to determine whether such an association is present in a community-dwelling Japanese population, including elderly and middle-aged individuals. This study used a cross-sectional design. Participants were 492 community-dwelling individuals aged ≥ 40 years living in Yuzawa Town, Japan. The health check examination was conducted in 2015, and serum 25-hydroxyvitamin D [25(OH)D, an index of vitamin D levels], and hand grip strength were measured. Covariates were serum albumin concentration, body mass index, and physical activity level. The associations of serum 25(OH)D concentrations with hand grip strength and low grip strength (< 26 kg for men and < 18 kg for women) were analyzed using analysis of covariance and multiple logistic regression. Mean (standard deviation) age and serum 25(OH)D were 75.4 (9.0) years and 30.9 (9.1) ng/mL, respectively. The prevalence of serum 25(OH)D < 20, 20-29, and ≥ 30 ng/mL was 7.3%, 37.8%, and 54.9%, respectively. Mean hand grip strength in the 25(OH)D < 20 ng/mL group was significantly lower than that in the ≥ 30 ng/mL group (adjusted P ≤ 0.001). The 25(OH)D < 20 ng/mL group was significantly more likely to have low grip strength than the 25(OH)D ≥ 30 ng/mL group (odds ratio = 4.12). In conclusion, low serum 25(OH)D concentration (< 20 ng/mL) is associated with low grip strength in an older Japanese population.

DOI： 10.1007/s00774-019-01040-w

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BACKGROUND: A large earthquake can cause extreme stress and may adversely affect cognitive function in humans. We aimed to examine a possible association between psychological distress and incident dementia after the 2004 Niigata-Chuetsu earthquake in Japan. METHODS: This is a retrospective cohort study followed participants for 10-12 years. Subjects were 6,012 residents in 2005, 5,424 in 2006, and 5,687 in 2007 (age ≥40 years) living in Ojiya city who participated in the annual health check examinations after the 2004 Niigata-Chuetsu earthquake. Psychological distress was assessed using the Kessler Psychological Distress Scale (K10), and individuals with a K10 score ≥10 were considered to have psychological distress. Incident dementia cases were identified from a long-term care insurance database of the local government during the follow-up period. We evaluated hazard ratios (HRs) of psychological distress for incident dementia in each year, unadjusted and adjusted for covariates, including sex, age, occupation, BMI, and property damage of residential area. RESULTS: The average age of the subjects was 64.6 years in 2005, 64.6 in 2006, and 65.2 in 2007. Adjusted HRs were significantly higher (HR = 1.20-1.66) in the psychological distress group than in the reference group in each year. In particular, adjusted HR was high (HR = 2.89) in those with psychological distress in all three years (2005-2007). CONCLUSION: Psychological distress, especially persistent distress, is a risk factor for incident dementia in victims of large disasters.

DOI： 10.1016/j.jad.2019.08.041

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OBJECTIVES: Modifiable risk factors for knee osteoarthritis (OA) have not been studied in detail. This study aimed to determine lifestyle-related modifiable factors of symptomatic knee osteoarthritis in an East Asian population. STUDY DESIGN: This 5-year cohort study involved 11,091 individuals (age range 40-72 years) living in the Murakami region of Niigata, Japan, who did not have a history of knee OA. At baseline, information on sociodemographic characteristics, body size, lifestyle, and living condition was obtained using a self-administered questionnaire. MAIN OUTCOME MEASURES: Incident symptomatic knee OA observed at hospitals and orthopaedic clinics in the five years to 2016. Clinical grades of knee OA were based on the Kellgren-Lawrence scale. P for trend was assessed to examine linear associations between predictors and the outcome in multiple logistic regression analysis. RESULTS: The mean age of participants was 58.1 (SD 9.3) years. The number of cases of grade 2 or more incident knee OA was 429. In men, older age (P for trend < 0.0001), higher BMI (P for trend < 0.0001), higher METs score (P for trend = 0.0150), less smoking (P for trend = 0.0249), and lower green tea consumption (P for trend = 0.0437) were associated with incident knee OA. In women, older age (P for trend < 0.0001), higher BMI (P for trend < 0.0001), and alcohol consumption (P = 0.0153) were associated with incident knee OA. CONCLUSIONS: Several lifestyle-related factors were found to be associated with incident knee OA and exhibited sex-dependent differences. In particular, higher consumption of green tea was associated with a lower incidence of knee OA in men.

DOI： 10.1016/j.maturitas.2019.06.013

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Language：Japanese   Publisher：(株)北隆館  

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DOI： 10.1007/s11657-019-0575-4

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DOI： 10.1007/s00198-018-4665-8

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

Background: Age-related musculoskeletal diseases are becoming increasingly burdensome in terms of both individual quality of life and medical cost. We intended to establish a large population-based cohort study to determine environmental, lifestyle, and genetic risk factors of musculoskeletal and other age-related diseases, and to clarify the association between vitamin D status and such diseases. Methods: We targeted 34,802 residents aged 40-74 years living in areas of northern Niigata Prefecture, including Sekikawa Village, Awashimaura Village, and Murakami City (Murakami region). The baseline questionnaire survey, conducted between 2011 and 2013, queried respondents on their lifestyle and environmental factors (predictors), and self-reported outcomes. Plasma 25-hydroxyvitamin D (25[OH]D) concentration, an indicator of vitamin D status, was determined with the Liaison® 25OH Vitamin D Total Assay. The primary outcome of this study was osteoporotic fracture
other outcomes included age-related diseases including knee osteoarthritis, perception of chronic pain, dementia, and long-term care insurance use. Mean ages of men and women were 59.2 (SD = 9.3, N = 6907) and 59.0 (SD = 9.3, N = 7457) years, respectively. From the blood samples provided by 3710 men and 4787 women, mean 25(OH)D concentrations were 56.5 (SD = 18.4) nmol/L (22.6 ng/mL) and 45.4 (SD = 16.5) nmol/L (18.2 ng/mL), respectively. Discussion: Follow-up surveys are planned every 5 years for 15 years, and incident cases of our targeted diseases will be followed at hospitals and clinics in and nearby the cohort area. We anticipate that we will be able to clarify the association between vitamin D status and multiple disease outcomes in a Japanese population.

DOI： 10.1186/s12199-018-0715-2

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Language：Japanese   Publisher：新潟医学会  

私たちは、健康寿命延伸とビタミンDの加齢性疾患予防効果の解明を目的として、加齢性運動器疾患、認知症、その他の疾患のリスク要因や予防要因を包括的に解明する地域住民コホート研究を2011年に新潟県村上保健所管内で開始した。エンドポイントは、死亡と疾患罹患率であり、対象疾患は、骨粗鬆症性骨折、変形性膝関節症、認知症、慢性疼痛、その他である。健康調査票によるベースライン調査に同意した参加者(n=14,364)の平均年齢は、男性59.2歳(SD=9.3、n=6,907)、女性59.0歳(SD=9.3、n=7,457)であった。また、血液検体のある参加者(n=8,497)の平均年齢は、男性56.5歳(SD=18.4、n=3,710)、女性45.4歳(SD=16.5、n=4,787)であった。調査票による5年後フォローアップ調査を2016〜2017年に行い(回収率61%)、疾患追跡を順調に進めている。(著者抄録)

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00990&link_issn=&doc_id=20181107040004&doc_link_id=%2Fdg3nigta%2F2018%2F013204%2F004%2F0127-0130%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2018%2F013204%2F004%2F0127-0130%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Publishing type：Research paper (scientific journal)   Publisher：Informa UK Limited  

DOI： 10.2147/JPR.S184746

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

Background
Few empirical studies have been conducted to identify modifiable factors that may affect cognitive impairment in Japanese individuals. The present study aimed to clarify whether body mass and lifestyle are associated with cognitive impairment in Japanese middle-aged and elderly individuals.
Methods
Subjects were 1814 community-dwelling individuals aged 44-79 years, all of whom were participants of the Murakami Cohort Study baseline survey conducted in 2011-2013. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) in 2014-2016, and cognitive impairment, the outcome measure, was defined as an MMSE score &lt;24. Predictor variables were body mass index (BMI), long-term weight changes from 20 years of age, and lifestyle factors, such as smoking, drinking, and physical activity levels, which were obtained from a self-administered questionnaire in the baseline survey. Covariates were sex, age, education level, and histories of stroke and diabetes. Multiple logistic regression analysis was used to calculate the adjusted odds ratios (ORs).
Results
The prevalence of overall cognitive impairment was 6.2%. The adjusted ORs of cognitive impairment in the lowest (&lt;[-4] kg) (OR = 2.70, 95% CI, 1.18-6.20) and second ([-4]-[0] kg) (OR = 2.37, 95% CI, 1.04-5.37) quintiles for long-term weight change were significantly higher than the reference 4th quintile ([+4]-[+7] kg). The adjusted OR in the highest quintile &gt;=[+8] kg) was 2.24 (95% CI, 0.99-5.04). Current BMI was not associated with cognitive impairment.
Conclusions
Long-term weight loss is associated with cognitive impairment in Japanese middle-aged and elderly individuals. Because the present study was retrospective in nature, prospective studies should also be conducted for further characterization of this association.

DOI： 10.1371/journal.pone.0185960

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Chondroitin sulfate (CS) is an important glycosaminoglycan and is mainly found in the extracellular matrix as CS proteoglycans. In the brain, CS proteoglycans are highly concentrated in perineuronal nets (PNNs), which surround synapses and modulate their functions. To investigate the importance of CS, we produced and precisely examined mice that were deficient in the CS synthesizing enzyme, CSGalNAcT1 (T1KO). Biochemical analysis of T1KO revealed that loss of this enzyme reduced the amount of CS by approximately 50% in various brain regions. The amount of CS in PNNs was also diminished in T1KO compared to wild-type mice, although the amount of a major CS proteoglycan core protein, aggrecan, was not changed. In T1KO, we observed abnormalities in several behavioral tests, including the open-field test, acoustic startle response, and social preference. These results suggest that T1 is important for plasticity, probably due to regulation of CS-dependent PNNs, and that T1KO is a good model for investigation of PNNs.

DOI： 10.1186/s13041-017-0328-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Ocular dominance plasticity is easily observed during the critical period in early postnatal life. Chondroitin sulfate (CS) is the most abundant component in extracellular structures called perineuronal nets (PNNs), which surround parvalbumin-expressing interneurons (PV-cells). CS accumulates in PNNs at the critical period, but its function in earlier life is unclear. Here, we show that initiation of ocular dominance plasticity was impaired with reduced CS, using mice lacking a key CS-synthesizing enzyme, CSGalNAcT1. Two-photon in vivo imaging showed a weaker visual response of PV-cells with reduced CS compared to wild-type mice. Plasticity onset was restored by a homeoprotein Otx2, which binds the major CS-proteoglycan aggrecan and promotes its further expression. Continuous CS accumulation together with Otx2 contributed bidirectionally to both onset and offset of plasticity, and was substituted by diazepam, which enhances GABA function. Therefore, CS and Otx2 may act as common inducers of both onset and offset of the critical period by promoting PV-cell function throughout the lifetime.

DOI： 10.1038/s41598-017-04007-x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

This study aimed to examine rural-urban differences in the prevalence of cognitive impairment in Japan.
We targeted 592 residents aged 65 years and older who did not use long-term care insurance services in one rural and two urban areas in Ojiya City, Japan. Of these, 537 (90.7 %) participated in the study. The revised Hasegawa's dementia scale (HDS-R) was used to assess cognitive function, and cognitive impairment was defined as a HDS-R score aecurrency sign20. Lifestyle information was obtained through interviews. The prevalence of cognitive impairment was compared according to the levels of predictor variables by odds ratios (ORs) calculated by a logistic regression analysis.
Mean age of participants was 75.7 years (SD 7.0). The prevalence of cognitive impairment was 20/239 (8.4 %) in the rural area and 6/298 (2.0 %) in the urban areas, for a total of 26/537 (4.8 %) overall. Men tended to have a higher prevalence of cognitive impairment (P = 0.0628), and age was associated with cognitive impairment (P for trend &lt; 0.0001). The rural area had a significantly higher prevalence of cognitive impairment (age- and sex-adjusted OR = 4.04, 95 % CI: 1.54-10.62) than urban areas. This difference was significant after adjusting for other lifestyle factors.
The prevalence of cognitive impairment was higher in the rural area relative to urban areas in Ojiya city. This regional difference suggests the existence of potentially modifiable factors other than lifestyle in relation to cognitive impairment.

DOI： 10.1007/s12199-016-0542-2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TOHOKU UNIV MEDICAL PRESS  

Diet and food intake play an important role in the development of osteoporosis. However, apart from calcium and vitamin D, how nutrients affect bone status is not fully understood. The purpose of this study was to determine cross-sectional and longitudinal associations between dietary intake and bone mineral density (BMD) in Japanese postmenopausal women. This 5-year cohort study included 600 community dwelling women aged 55-74 years at baseline in 2005. Information on demographics, nutrition, and lifestyle was obtained through interviews, and nutritional and dietary intake was assessed using a validated food frequency questionnaire. BMD measurements were performed by dual energy X-ray absorptiometry. In 2010, 498 women underwent follow-up BMD examinations. Multiple linear regression analysis was performed to determine associations of predictor variables with BMD, adjusting for confounders. In cross-sectional analyses, coffee or black tea consumption was positively associated with lumbar spine (P = 0.004) and total hip (P = 0.003) BMD, and alcohol intake was positively associated with femoral neck (P = 0.005) and total hip (P = 0.001) BMD. In longitudinal analyses, vitamin K (P = 0.028) and natto (fermented soybeans) (P = 0.023) were positively associated with lumbar spine BMD, and meat or meat product consumption was inversely associated with total hip (P = 0.047) BMD. In conclusion, dietary factors other than calcium and vitamin D intake are predictors of bone mass and bone loss in Japanese postmenopausal women. In particular, natto intake is recommended for preventing postmenopausal bone loss on the basis of current evidence.

DOI： 10.1620/tjem.239.95

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

Background/Aims: Evidence on modifiable factors associated with cognitive impairment in Japanese patients is scarce. This study aimed to determine modifiable factors for cognitive impairment in a Japanese hospital-based population. Methods: Subjects of this cross-sectional study were 1,143 patients of Sado General Hospital (Niigata, Japan) registered in the Project in Sado for Total Health (PROST) between June 2008 and September 2014. We assessed disease history, body mass index (BMI), leisure time physical activity, walking time, smoking and drinking habits, and consumption of vegetables, fruits, and green tea as predictors, with cognitive impairment defined by the Mini-Mental State Examination (score &lt
24) as an outcome. Multiple logistic regression analysis was performed to calculate odds ratios (ORs) for cognitive impairment. Results: The mean subject age was 68.9 years, and the prevalence of cognitive impairment was 21.5%. Multivariate analysis revealed that age (p &lt
0.001), low BMI (&lt
21.1
OR 1.39, 95% CI 1.12-1.72), a history of stroke (p = 0.003), a history of myocardial infarction (p = 0.038), low fruit consumption (p for trend = 0.012), and low green tea consumption (p for trend = 0.032) were independently associated with a higher prevalence of cognitive impairment. Conclusions: Modifiable factors, such as low BMI, low fruit consumption, and low green tea consumption, are associated with cognitive impairment. Longitudinal studies will be needed to confirm these findings.

DOI： 10.1159/000447963

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Background: Little is known about correlates of vitamin D status in Asian populations. In this study, we established the prevalence of vitamin D sufficiency in the Murakami region (latitude N38 degrees 13') in Niigata, Japan, and examined demographic, environmental, and lifestyle factors that might be associated with vitamin D sufficiency, with the aim of clarifying the relative contributions of previously described determinants of vitamin D status as well as identifying new determinants in this Japanese population.
Methods: This study involved a cross-sectional analysis of baseline data obtained from a cohort study conducted in 2011-2013. Participants were 9084 individuals aged between 40 and 74 years who provided blood samples for the determination of plasma 25-hydroxyvitamin D [25(OH)D] concentrations. Lifestyle information was obtained from 8498 participants, with some missing values regarding different lifestyle factors. Multiple logistic regression analysis was used to obtain odds ratios for vitamin D sufficiency, which was defined as a plasma 25(OH)D concentration &gt;= 75 nmol/L.
Results: The prevalence of vitamin D sufficiency (i.e., plasma 25(OH)D concentration &gt;= 75 nmol/L) was 9.1%, and significant associations were observed with male gender (P &lt;0.0001; OR = 2.37, 95% CI: 1.84-3.05), older age (P for trend &lt;0.0001), lower BMI (P for trend &lt;0.0001), higher METs score (P for trend = 0.0138), higher vitamin D intake (P for trend = 0.0467), summer season (P for trend &lt;0.0001), longer duration outdoors (P for trend = 0.0026), no sunscreen use (P = 0.0135; OR = 1.40, 95% CI: 1.07-1.82), higher salmon consumption (P for trend &lt;0.0001), higher alcohol consumption (P for trend &lt;0.0001), and lower coffee consumption (P for trend = 0.0025). Unlike other populations previously reported, vitamin D sufficiency was associated with older age.
Conclusions: The prevalence of vitamin D sufficiency (i.e., 25[OH]D &gt;= 75 nmol/L) was low (9.1%) in this Japanese population. A number of demographic, environmental, and lifestyle factors are associated with vitamin D sufficiency, and thus lifestyle modification may present an opportunity to achieve vitamin D sufficiency. (c) 2015 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bone.2014.12.064

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Extracellular factors that inhibit axon growth and intrinsic factors that promote it affect neural regeneration. Therapies targeting any single gene have not yet simultaneously optimized both types of factors. Chondroitin sulphate (CS), a glycosaminoglycan, is the most abundant extracellular inhibitor of axon growth. Here we show that mice carrying a gene knockout for CS N-acetylgalactosaminyltransferase-1 (T1), a key enzyme in CS biosynthesis, recover more completely from spinal cord injury than wild-type mice and even chondroitinase ABC-treated mice. Notably, synthesis of heparan sulphate (HS), a glycosaminoglycan promoting axonal growth, is also upregulated in TI knockout mice because HS-synthesis enzymes are induced in the mutant neurons. Moreover, chondroitinase ABC treatment never induces HS upregulation. Taken together, our results indicate that regulation of a single gene, T1, mediates excellent recovery from spinal cord injury by optimizing counteracting effectors of axon regeneration-an extracellular inhibitor of CS and intrinsic promoters, namely, HS-synthesis enzymes.

DOI： 10.1038/ncomms3740

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：PORTLAND PRESS LTD  

CS (chondroitin sulfate) is a glycosaminoglycan species that is widely distributed in the extracellular matrix. To understand the physiological roles of enzymes involved in CS synthesis, we produced CSGalNAcT1 (CS N-acetylgalactosaminyltransferase 1)-null mice. CS production was reduced by approximately half in CSGalNAcT1-null mice, and the amount of short-chain CS was also reduced. Moreover, the cartilage of the null mice was significantly smaller than that of wild-type mice. Additionally, type-II collagen fibres in developing cartilage were abnormally aggregated and disarranged in the homozygous mutant mice. These results suggest that CSGalNAcT1 is required for normal CS production in developing cartilage.

DOI： 10.1042/BJ20100847

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Choroid plexus (CP) epithelial cells (CPECs) produce cerebrospinal fluid (CSF) to provide the CNS with a specialized microenvironment. Our previous study showed that the conditioned medium of cultured CPECs enhanced the survival and neurite extension of hippocampal neurons. The present study examined the ability of cultured CPECs to protect against ischemic brain injury when transplanted into the CSF. Rats were subjected to a transient occlusion of the middle cerebral artery, followed by an injection of cultured CPECs into the fourth ventricle. The injection markedly reduced neurological deficits and infarction volume within 24 h. Other beneficial effects were (1) a reduction in number of apoptotic and inflammatory cells, (2) an up-regulation of the mRNA expression of an anti-apoptotic effecter, cAMP-response element binding protein, and (3) a down-regulation of the production of pro-inflammatory factors such its interleukin-1 beta and inducible nitric oxide synthase. The injected CPECs were located within the ventricles and on the brain&apos;s surface, not in the ischemic foci, suggesting that they exert their effects by releasing diffusible neuroprotective factors into the CSF. The transplantation of CPECs via CSF is a potential new strategy for protecting against ischemic brain injury. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2009.09.060

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MARY ANN LIEBERT INC  

Neural cell transplantation, a new therapeutic strategy for replacing injured neural components and obtaining functional recovery, has shown beneficial effects in animal models. Use of this strategy in human patients, however, requires that a number of serious issues be addressed, including ethics, immunorejection, and the therapeutic time window within which the procedure will be effective. Bone marrow-derived mononuclear cells (BM-MNC) are attractive for transplantation because they can be used as an autograft, can be easily collected within a short time period, and do not have to be cultured. In a rat model of spinal cord injury (SCI), we transplanted BM-MNC at 1 h after SCI at Th 8-9 by injecting them into the cerebrospinal fluid (CSF), and investigated the effect of this on neurologic function. In the acute stage of injury, we found a neuroprotective antiapoptotic effect, with an elevated concentration of hepatocyte growth factor in CSF. At I week after transplantation, the Basso-Beattie-Bresnahan locomotor score had increased significantly over its baseline value. In the chronic stage of injury, we observed suppressed cavity formation and functional improvement. We conclude that transplantation of BM-MNC after SCI has a remarkable neuroprotective effect in the acute stage of injury, suppressing cavity formation, and contributing to functional recovery. Our results suggest that transplantation of BM-MNC via the CSF is a potentially effective means of enhancing functional recovery after SCI in humans.

DOI： 10.1089/neu.2007.132R

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

The choroid plexus epithelial (modified ependymal) cells (CPECs) are specialized for cerebrospinal fluid (CSF) production and serve as blood-CSF barrier. It is suggested that, in addition to CSF production, the CPECs may regulate CNS function through expression of secretory factors into CSF. There have been reports that the CPECs express various types of factors including growth factors. However, the actual effects of the molecules produced and secreted from the CPECs on the central nervous system (CNS) are virtually unknown both in vivo and in vitro. With the use of pure culture of CPECs, we demonstrated that the conditioned medium (CM) from CPECs can enhance neurite outgrowth and survival of cultured neurons derived from rat hippocampus on postnatal day 1 in 24-h cultures. The effect of the CM was retained in fractions that contains complex of molecules larger than 50 kDa in native condition with ultrafiltration method and disappeared by trypsin digestion. The results of the present study indicate that CPECs can support the survival and function of neurons in vitro by secreting factors that are likely to be of peptide/protein nature rather than small chemicals. &COPY; 2004 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2004.12.068

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT  

Repressor element 1 (RE1)-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) can repress several terminal neuronal differentiation genes by binding to a specific DNA sequence (RE1/ neuron-restrictive silencer element [NRSE]) present in their regulatory regions. REST-VP16 binds to the same RE1/NRSE, but activates these REST/NRSF target genes. However, it is unclear whether REST-VP16 expression is sufficient to cause formation of functional neurons either from neural stem cells or from heterologous stem cells. Here we show that the expression of REST-VP16 in myoblasts grown under muscle differentiation conditions blocked entry into the muscle differentiation pathway, countered endogenous REST/NRSF-dependent repression, activated the REST/NRSF target genes, and, surprisingly, activated other neuronal differentiation genes and converted the myoblasts to a physiologically active neuronal phenotype. Furthermore, in vitro differentiated neurons produced by REST-VP16-expressing myoblasts, when injected into mouse brain, survived, incorporated into the normal brain, and did not form tumors. This is the first instance in which myoblasts were converted to a neuronal phenotype. Our results suggest that direct activation of REST/NRSF target genes with a single transgene, REST-VP16, is sufficient to activate other terminal neuronal differentiation genes and to override the muscle differentiation pathways, and they suggest that this approach provides an efficient way of triggering neuronal differentiation in myoblasts and possibly other stem cells.

DOI： 10.1101/gad.1179004

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING LTD  

The linker protein LAT is expressed mainly in T and natural killer (NK) cells. LAT-deficient mice have an arrest of intrathymic T-cell development at the CD4(+) CD8(+) stage and lack mature T cells in the periphery. However, no gross abnormality in expressed in mouse progenitor B (pro-B) and precursor B (pre-B) cells, but not in immature or mature B cells. LAT in pre-B cells becomes tyrosine phosphorylated upon cross-linking of the pre-B-cell receptor (pre-BCR) by anti-mu anti-body. Incubation of 1xN/2b (mouse pre-B-cell line) cells or bone marrow cells from muMT/muMT mice, which lack B cells after the small pre-B-cell stage, with anti-Igbeta antibody resulted in the downregulation of LAT expression. Transgenic mice which expressed LAT protein in B-lineage cells showed an increased proportion of pro- and large pre-B cells in the bone marrow and a remarkable reduction in the numbers of mature B cells in peripheral lymphoid tissues. Collectively, the present results indicate that LAT is expressed in the cells at the early stages of B-lineage development, but is absent in immature and mature B cells. LAT may play a crucial role in the negative regulation of B-cell development at the transition from pre-B to mature B-cell stages, and signal(s) via the pre-BCR may extinguish LAT expression, thus allowing pre-B-cell differentiation towards the mature B-cell stage.

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

The retinoblastoma protein (pRb) is a key regulator of cell growth, differentiation and survival. pRb(-/-) mice show abnormal neuronal cell death in the developing brain. The function of pRb is regulated by its phosphorylation state. In this study, the phosphorylation of pRb during retinoic acid (RA)-induced neuronal differentiation of P19 cells was examined using site-specific antibodies against pRb phosphorylated at Ser601, Ser605 and Ser773. Although pRb was hyperphosphorylated in undifferentiated P19 cells, Ser601 and Ser773 were not phosphorylated. Upon exposure to RA, however, these two sites became strongly phosphorylated, Cdk4 kinase activity was almost undetectable in undifferentiated P19 cells, but was strongly activated on exposure to RA. In contrast, Cdk2 kinase activity and the phosphorylation of Ser605 were observed in undifferentiated cells as well as in RA-treated cells. These observations suggest that Cdk2 and Cdk4 may phosphorylate different sites of pRb in vivo and that the two sites of pRb examined here are newly phosphorylated during RA-induced neuronal differentiation in P19 cells. (C) 1999 Elsevier Science B.V. All rights reserved.

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Language：Japanese   Publisher：(公財)先進医薬研究振興財団  

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Language：Japanese   Publisher：(一社)日本衛生学会  

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Language：Japanese   Publisher：(一社)日本認知症学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：SPRINGER LONDON LTD  

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Language：Japanese  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.neures.2011.07.1399

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.neures.2010.07.1108

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.neures.2010.07.1024

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.neures.2009.09.842

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.neures.2009.09.705

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Language：Japanese   Publisher：(有)科学評論社  

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Event date： 2021.3

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