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This study aimed to clarify the effects of the accumulation of 8 modifiable practices related to health, including smoking, alcohol drinking, physical activity, sleeping hours, body mass index, dietary diversity, ikigai (life worth living), and health checkup status, on higher-level functional capacity decline among Japanese community dwellers. Data were derived from the National Institute for Longevity Sciences - Longitudinal Study of Aging. Subjects comprised 1269 men and women aged 40 to 79 years at baseline (1997–2000) who participated in a follow-up postal survey (2013). Higher-level functional capacity was measured using the Tokyo Metropolitan Institute of Gerontology Index of Competence (total score and 3 subscales: instrumental self-maintenance, intellectual activity, and social role). The odds ratio (OR) and 95% confidence interval (CI) for a decline in higher-level functional capacity in the follow-up study according to the total number of healthy practices were analyzed using the lowest category as a reference. Multivariate adjusted ORs (95% CIs) for the total score of higher-level functional capacity, which declined according to the total number of healthy practices (0–4, 5–6, 7–8 groups) were 1.00 (reference), 0.63 (0.44–0.92), and 0.54 (0.31–0.94). For the score of social role decline, multivariate adjusted ORs (95% CIs) were 1.00 (reference), 0.62 (0.40–0.97), and 0.46 (0.23–0.90), respectively (P for trend = 0.04). Having more modifiable healthy practices, especially in social roles, may protect against a decline in higher-level functional capacity among middle-aged and elderly community dwellers in Japan., Highlights • Each healthy practice was not necessarily associated with functional capacity. • Having 5 to 8 healthy practices might favor higher-level functional capacity. • Having healthy practices may protect against decline in social role.

The longitudinal relationship between cognitive abilities and subsequent death was investigated among community-dwelling older Japanese adults.Participants (n = 1060; age range 60-79 years) comprised the first-wave participants of the National Institute for Longevity Sciences-Longitudinal Study of Aging. Participants' cognitive abilities were measured at baseline using the Japanese Wechsler Adult Intelligence Scale-Revised Short Form, which includes the following tests: Information (general knowledge), Similarities (logical abstract thinking), Picture Completion (visual perception and long-term visual memory) and Digit Symbol (information processing speed). By each cognitive test score, participants were classified into three groups: the high-level group (≥ the mean + 1SD), the low-level group (≤ the mean - 1SD) and the middle-level group. Data on death and moving during the subsequent 15 years were collected and analyzed using the multiple Cox proportional hazard model adjusted for physical and psychosocial covariates.During the follow-up period, 308 participants (29.06%) had died and 93 participants (8.77%) had moved. In the Similarities test, adjusted hazard ratios (HR) of the low-level group to the high-level group were significant (HR 1.49, 95% CI 1.02-2.17, P = 0.038). Furthermore, in the Digit symbol test, the adjusted HR of the low-level group to the high-level group was significant (HR 1.62, 95% CI 1.03-2.58, P = 0.038). Significant adjusted HR were not observed for the Information or Picture Completion tests.It is suggested that a lower level of logical abstract thinking and slower information processing speed are associated with shorter survival among older Japanese adults. Geriatr Gerontol Int 2017; 17: 1654-1660.

The association between sarcopenia diagnosed according to the criteria of the Asian Working Group for Sarcopenia and increased mortality risk is currently unknown. The present study assessed the longitudinal relationship between sarcopenia and mortality risk in an elderly Japanese population.Participants were 720 community-dwelling Japanese individuals aged 65-79 years at baseline (November 1997 to April 2000). The participants were followed from baseline to 31 December 2014 (mean duration 11.0 years). Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia criteria, using extremity muscle mass assessed by dual-energy X-ray absorptiometry, grip strength and gait speed. A population dynamics survey was used to obtain information on deaths. The relationship between sarcopenia and mortality was assessed using Kaplan-Meier survival curves and Cox proportional hazards regression. The Cox proportional hazards model was used to control for potential confounders, including age at baseline, body mass index, total caloric intake, alcohol intake, current smoking habits, leisure-time physical activity and the number of current diseases.The fully adjusted hazard ratio for all-cause mortality among men in the sarcopenia group was 1.95 (95% confidence interval 1.04-3.67) compared with that in the normal group. No significant association between sarcopenia and all-cause mortality was observed among women.The complications of sarcopenia, including low muscle mass, low grip strength and low gait speed, appear to be significant risks for mortality in older Japanese men. Geriatr Gerontol Int 2017; 17: 1642-1647.

Aim The longitudinal relationship between cognitive abilities and subsequent death was investigated among community-dwelling older Japanese adults. Methods Participants (n = 1060; age range 60–79 years) comprised the first-wave participants of the National Institute for Longevity Sciences-Longitudinal Study of Aging. Participants’ cognitive abilities were measured at baseline using the Japanese Wechsler Adult Intelligence Scale-Revised Short Form, which includes the following tests: Information (general knowledge), Similarities (logical abstract thinking), Picture Completion (visual perception and long-term visual memory) and Digit Symbol (information processing speed). By each cognitive test score, participants were classified into three groups: the high-level group (≥ the mean + 1SD), the low–level group (≤ the mean – 1SD) and the middle-level group. Data on death and moving during the subsequent 15 years were collected and analyzed using the multiple Cox proportional hazard model adjusted for physical and psychosocial covariates. Results During the follow-up period, 308 participants (29.06%) had died and 93 participants (8.77%) had moved. In the Similarities test, adjusted hazard ratios (HR) of the low-level group to the high-level group were significant (HR 1.49, 95% CI 1.02–2.17, P = 0.038). Furthermore, in the Digit symbol test, the adjusted HR of the low-level group to the high-level group was significant (HR 1.62, 95% CI 1.03–2.58, P = 0.038). Significant adjusted HR were not observed for the Information or Picture Completion tests. Conclusions It is suggested that a lower level of logical abstract thinking and slower information processing speed are associated with shorter survival among older Japanese adults. Geriatr Gerontol Int 2017; 17: 1654–1660.

The etiologies of idiopathic sudden sensorineural hearing loss (SSNHL) and Ménière's disease remain unclear. Recently, accumulating evidence has demonstrated that oxidative stress is related to the pathology of inner ear disease. Because genetic factors may contribute partly to the etiologies of SSNHL and Ménière's disease, we investigated the associations between genetic polymorphisms located in oxidative stress response genes and susceptibility to SSNHL and Ménière's disease. We compared 84 patients affected by SSNHL, 82 patients affected by Ménière's disease, and 2107 adults (1056 men and 1051 women; mean age, 59.2 years; range, 40-79 years) who participated in the National Institute for Longevity Sciences, Longitudinal Study of Aging. Multiple logistic regression was used to calculate odds ratios for SSNHL and Ménière's disease in individuals with polymorphisms in the genes glutathione peroxidase 1 (GPX1) (Pro198Leu, rs1050450), paraoxonase 1 (PON1) (Gln192Arg, rs662; and Met55Leu, rs854560), PON2 (Ser311Cys, rs7493), and superoxide dismutase 2 (SOD2) (Val16Ala, rs4880), with adjustment for age and gender. No significant differences in the distribution of the genotypes at these polymorphisms were observed among individuals with SSNHL and Ménière's disease and controls. No significant risk for SSNHL and Ménière's disease was observed in the additive genetic model, regardless of moderating variables. The C allele of SOD2 (rs4880) was more frequent in Ménière's disease cases with a hearing level over 50 dB compared with cases with a hearing level below 50 dB, suggesting that this polymorphism is associated with progression of a hearing loss in Ménière's disease. In conclusion, no significant associations between the polymorphisms of GPX1, PON1, PON2, and SOD2 and risk of SSNHL and Ménière's disease were observed in this Japanese case-control study.

We studied the relationship between fatty acid-binding protein 3 (FABP3) and obesity in vivo and the effects of FABP3 on signal transduction for glucose uptake in skeletal muscle cells in vitro. In obese mice, the level of FABP3 protein in gastrocnemius muscles increased significantly with an increase in body weight and metabolic phenotypes, suggesting a close relationship between FABP3 expression in the muscle and the development of obesity and/or insulin resistance in mice. In experiments using C2C12 myotubes infected with adenoviruses encoding human FABP3, induction stimulated glucose uptake without insulin stimulation in parallel with increases in the phosphorylation of AMP-activated protein kinase (AMPK) and AS160. Insulin enhanced glucose uptake in an additive fashion with increased phosphorylation of Akt and AS160 in FABP3-induced myotubes compared to control cells. This increased glucose uptake in FABP3-induced myotubes with insulin stimulation was found even in the presence of palmitate, in which a significantly higher Akt phosphorylation was detected compared to controls. These results suggest that FABP3 stimulates glucose uptake by facilitating AMPK-dependent AS160 phosphorylation in skeletal muscle. FABP3 may also contribute to AS160 phosphorylation by maintaining insulin-dependent Akt activation in the cells under a lipotoxic condition.

Aim: To describe age- and sex-related differences in gait patterns of community-living men and women using 3-D gait analysis. Methods: Subjects (n = 2006) aged 40–84 years participated in the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA). Spatiotemporal components, including velocity, step length, step frequency, and double support time during a gait cycle, were calculated from 3-D coordinates and vertical force data. Velocity, step length and step frequency were normalized by leg length and acceleration due to gravity, and double support time was normalized to gait cycle duration. Results: Spatiotemporal walking variables of brisk velocity and step length were significantly greater in men than in women, while comfortable velocity and comfortable and brisk step frequencies and double support times were greater in women than in men. Age-related changes were marked at 70–84 years in most spatiotemporal variables in both sexes during comfortable walking. During brisk walking, age-related changes were observed from a younger age than during comfortable walking, and there were sex-related differences. Conclusion: The age-related gait alteration was obvious among those aged 70 years and older, and it accelerated markedly in women's brisk walking intensity. Geriatr Gerontol Int 2011; 11: 39–49.

It remains unclear whether n-3 long-chain polyunsaturated fatty acids (LCPUFA) have a preventive effect on depression in the general population. This study investigated the longitudinal association between n-3 LCPUFA intake and depressive symptoms in community-dwelling Japanese participants. The participants were aged 40&ndash, 79 years at baseline in the cohort study, wherein examinations, including the assessment of depressive symptoms and nutritional status, were biennially conducted from 1997 to 2012. The subjects (n = 2335) who had a Center for Epidemiologic Studies Depression Scale (CES-D) score &lt, 16 at the first examination and who participated in the follow-up study at least once were included in the analysis. The follow-up end point was the first onset (CES-D &ge, 16) or the last examination participation. Hazard ratios (95% CIs) for CES-D &ge, 16 were estimated using the adjusted Cox proportional hazards model. Overall, 22.1% participants showed depressive symptoms during follow-up (average, 8.1 years). Compared with the lowest tertile, the highest HR for EPA was 0.74 (0.60&ndash, 0.93), and highest and middle HRs for DHA were 0.79 (0.63&ndash, 0.98) and 0.80 (0.65&ndash, 0.99) (P for trend = 0.009 and 0.032), respectively. Among populations with high fish consumption, higher n-3 LCPUFA intake may be associated with a low risk of depressive symptoms.

Objectives Arterial sclerosis contributes to inadequate blood supply to multiple organs, suggesting that general atherosclerosis may play an important role in the inner ear. Since noise is a major etiology for hearing loss, the aim of this study was to evaluate both the respective and the combined effects of arterial sclerosis and occupational noise exposure on hearing after accounting for age in middle-aged and elderly men. Methods The evaluation was conducted using 773 subjects from a population-based sample of 1189 men, aged 40–83 years. The impact of carotid atherosclerosis (CA) or retinal arteriolosclerosis (RA) on hearing was assessed according to history of occupational noise exposure (Noise) obtained in a questionnaire. Differences in the mean pure-tone thresholds at each frequency, between the CA (+) and CA (−) groups or between the RA (+) and RA (−) groups, based on noise exposure were compared using the general linear model (GLM) Procedure in SAS, with adjustments for age. Then, the main effect of CA or RA, and the interactive effect of noise and either CA or RA on pure-tone threshold at seven frequencies were analyzed using an analysis of covariance (ANCOVA), after adjusting for age. Results In the Noise (+) group, a statistically significant deterioration in hearing was found in the CA (+) group compared with the CA (−) group at 500 and 1000 Hz. The results in RA were significant at even lower frequencies than in CA. In the results from ANCOVA, the significant main effect of CA was shown in the pure-tone threshold at 8000 Hz, but not in the analysis of RA. A significant interactive effect of either CA or RA and Noise was observed in hearing at the range from 125 to 1000 Hz. Conclusions The present study suggests that the impact of arterial sclerosis on hearing is limited but significantly hazardous in middle-aged and elderly men, and that arterial sclerosis exacerbates the deleterious effects of noise on hearing. Early recognition of arterial sclerosis might be contributory to the hearing prognosis after middle age, especially for noise-exposed men.

Objective The fatty acid-binding protein 2 (FABP2) is involved in the transport and metabolism of fatty acids. The FABP2 gene has been proposed as a candidate gene for diabetes and obesity. This study evaluates the hearing impairment risk in the Ala54Thr polymorphism of FABP2 in middle-aged and elderly Japanese. Methods Our sample population comprised 1428 community-dwelling Japanese aged 40–86 years (mean ± standard deviation [SD]: 63.1 ± 9.8) who participated in the Study of Aging between 2004 and 2006. An average hearing threshold level greater than 25 dB in the better ear for frequencies 500, 1000, 2000 and 4000 Hz was defined as hearing impairment. Data were analyzed by means of a multiple logistic regression with adjustment for potential confounders. Results The per-allele odds ratio for hearing impairment risk was 1.262 (95% confidence interval [CI]: 1.012–1.574) in model 1, adjusting for age, sex, history of ear disease, and history of occupational noise exposure; and 1.259 (CI: 1.009–1.571) in model 2, which adjusted for diabetes, body mass index and the histories of heart disease and hypertension, as well as the moderators in model 1. A significant adverse effect of the Thr54 variant on hearing was observed and the effect was independent of both diabetes and obesity in the present analyses. Conclusions This study demonstrated that the Ala54Thr polymorphism of FABP2 was associated with a risk of hearing impairment in middle-aged and elderly people. The results might support caloric restriction theory indirectly, but additional researches are desired.

Objectives/Hypothesis: To investigate the recently reported association of the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene with sudden sensorineural hearing loss (SSNHL), we analyzed data from a community-based Japanese population. Study Design: Nested case-control study. Methods: Among 2,174 adults (1,096 males and 1,078 females) aged 40 to 79 years old who participated in the National Institute for Longevity Sciences–Longitudinal Study of Aging, we compared 33 cases of prevalent SSNHL, defined as a self-reported otolaryngologist diagnosis, with the other cases. Multiple logistic regression was used to obtain odds ratios (ORs) for SSNHL in subjects with the MTHFR C677T polymorphism, with adjustment for other possibly influential factors under additive, dominant, and recessive genetic models. Results: The per-allele ORs for SSNHL risk were 1.687 (95% confidence interval [CI], 1.023–2.780) in model 1, with adjustment for age and sex, and 1.654 (CI, 1.003–2.728) in model 2, with adjustment for smoking status, body mass index, histories of heart disease, hypertension, and diabetes, in addition to the factors in model 1. In model 3, a significant association between SSNHL and the C677T polymorphism was observed under all genetic models independent of factors including folic acid and homocysteine, although there were only 25 cases and 1,677 controls due to the addition of moderating factors. Conclusions: Our results suggest that the T allele of MTHFR C677T could be associated with susceptibility to SSNHL, and even imply that this mutation could be a risk factor that is independent of blood folic acid and homocysteine. Laryngoscope, 2010

This study illustrates that UCP2 Ala55Val polymorphisms exhibit a significant association with age-related hearing loss in the Japanese population.Mitochondrial uncoupling proteins (UCPs) have been suggested to play a protective role against neuron oxidative damage and a thermal signaling role in neuron modulation in the inner ear. In the current study, we examined the relationship between gene polymorphisms in UCP1 and UCP2 and hearing impairment (HI) in Japanese elderly.A total of 1547 subjects aged 40-79 years and living in Aichi prefecture, Japan, were entered into this study. Subjects were followed up every 2 years, and the cumulative number of subjects for 3 sequential examinations in 6 years was 4942 persons. Detailed questionnaires, pure-tone audiometry measurements, and UCP1 A-3826G and UCP2 Ala55Val polymorphisms were examined. Using generalized estimating equations, associations between HI and gene polymorphisms in UCP1 and UCP2 with age, sex, history of occupational noise exposure, and body mass index were analyzed under dominant, recessive, and additive models.UCP1 A-3826G polymorphism did not exhibit any significant association with HI. However, UCP2 Ala55Val polymorphism did exhibit a significant association with HI under all the dominant (p = 0.0167), recessive (p = 0.0411), and additive (p = 0.0061) models.

Previous studies have indicated low serum carotenoid concentrations among cigarette smokers and/or alcohol drinkers, but little is known about the interaction of smoking and drinking with serum carotenoids. We tested the hypothesis that smoking and drinking reduce serum carotenoid concentrations synergistically. A total of 1073 subjects (357 male and 716 female) who had received health examinations in the town of Mikkabi, Shizuoka Prefecture, Japan, participated in the study. The subjects were divided into six groups according to alcohol intake (non-drinkers,1 g/d; light drinkers,or = 1,25 g/d; moderate-to-heavy drinkers,or = 25 g/d) and smoking status (non-smokers and current smokers). The dietary intakes and serum concentrations of six carotenoids (lycopene, alpha-carotene, beta-carotene, lutein, beta-cryptoxanthin and zeaxanthin) within each group were evaluated cross-sectionally. The dietary intakes of all carotenoids did not differ in the six groups after adjusting for age and sex. The multivariate-adjusted means of the serum carotenoid concentrations in non-drinkers did not differ between non-smokers and current smokers. In contrast, the adjusted means of serum alpha-carotene, beta-carotene and beta-cryptoxanthin were significantly lower than those with increased alcohol intake, and these lower serum carotenoids among alcohol drinkers were more evident in current smokers than in non-smokers. Serum lycopene of moderate-to-heavy drinkers was significantly lower than that of non-drinkers, but it was not influenced by smoking. Neither smoking nor drinking was associated with the serum concentrations of lutein and zeaxanthin. These results suggest that smoking and drinking may reduce the serum alpha-carotene, beta-carotene and beta-cryptoxanthin concentrations in a synergistic manner.

Recent epidemiological studies show the associations of serum antioxidant status with the metabolic syndrome. Oxidative stress may play an important role in the pathogenesis of diabetes and CVD. Actually, smoking is a potent oxidative stressor in man, but little is known about the interaction of serum carotenoids and the metabolic syndrome with smoking status. In this study, the associations of the serum carotenoids with the metabolic syndrome stratified by smoking habit were evaluated cross-sectionally. A total of 1073 subjects (357 male and 716 female) who had received health examinations in the town of Mikkabi, Shizuoka Prefecture, Japan, participated in the study. Among total subjects, the OR for the metabolic syndrome in the highest tertile of serum β-carotene was 0·41 (95 % CI 0·18, 0·92) after adjusting confounders. In current smokers, significantly lower OR were observed in the middle (OR 0·10; 95 % CI 0·01, 0·72) and highest (OR 0·06; 95 % CI 0·01, 0·73) tertiles of serum β-carotene. Furthermore, lower OR were observed in accordance with tertiles of serum α-carotene and β-cryptoxanthin in current smokers (P for trend 0·042 and 0·036, respectively). In contrast, in non-smokers, a significantly lower OR was observed in the highest tertile of serum β-carotene (OR 0·30; 95 % CI 0·10, 0·89) after multiple adjustment. Inverse associations of serum carotenoids with the metabolic syndrome were more evident among current smokers than non-smokers. These results support that antioxidant carotenoids may have a protective effect against development of the metabolic syndrome, especially in current smokers who are exposed to a potent oxidative stress.

Background: There has been much interest in the role of free radicals and oxidative stress in the pathogenesis of metabolic syndrome (MetS). Cellular antioxidant enzymes such as glutathione peroxidase 1 (GPX1) play a central role in the control of reactive oxygen species. Objective: We examined whether GPX1 polymorphism (Pro198Leu) is associated with MetS as well as with each component of MetS. Design: The study was a cross-sectional analysis of randomly selected, community-dwelling Japanese persons aged 40-70 y (1128 M, 1105 F). Results: The genotype frequencies for the GPX1 Prol98Leu polymorphism in this cohort were 0.846, 0.151, and 0.003 for CC, CT, and TT, respectively. The CT/TT genotypes had significantly higher waist-hip ratios, triacylglycerol concentrations, homeostasis model assessment for β-cell function, and systolic and diastolic blood pressures in men (P = 0.045, 0.012, 0.011, 0.004, and 0.003, respectively) than did the CC genotype; the CC/TT genotypes also had higher insulin in both sexes (P = 0.019 for men, P = 0.010 for women) and higher body fat mass (P = 0.027) and homeostasis model assessment for insulin resistance (P = 0.008) in women. The CT/TT genotypes showed significant association with higher prevalence of MetS as defined by 2 commonly used criteria in men [odds ratio (OR): 2.02; 95% CI: 1.30, 3.15 by the International Diabetes Federation criteria; OR: 1.49; 95% CI: 1.02, 2.18 by the modified National Cholesterol Education Program criteria) but not in women. The CT/TT genotypes showed a higher prevalence of central obesity (OR: 1.93; 95% CI: 1.31,2.85) and hypertriglyceridemia (OR: 1.52; 95% CI: 1.08, 2.15) in men but not in women; there were no differences in other components of MetS between the CC and CT/TT genotypes in either sex. Conclusion: GPX1 Prol98Leu variants are associated with the prevalence of MetS in Japanese men but not in women.

There is evidence of an inverse association between cerebral infarction and tinnitus in this study. The effects of cerebral infarction on tinnitus could be explained by a neurophysiological model of tinnitus.We examined the relationship between tinnitus and brain MRI findings including cerebral infarction, brain atrophy, ventricular dilatation, and white matter lesions.This was a cross-sectional population-based study of 2193 subjects aged 41-82 years living in Aichi prefecture, Japan. Detailed questionnaires, pure tone audiometry, and brain MRI were performed.After adjusting for potential confounders in a multiple logistic analysis, cerebral infarction was inversely associated with tinnitus (odds ratio (OR)=0.649, 95% confidence interval (CI)=0.477-0.884). Cerebral infarctions of the basal ganglia (OR=0.542), thalamus (OR=0.441), and pons (OR=0.319) were especially associated with tinnitus. Brain atrophy, ventricular dilatation, and white matter lesions had no significant effects on the prevalence of tinnitus.

Because both genetic and environmental factors influence bone mass, it is important to examine the effect of gene-environment interactions on bone mineral density (BMD) for the prevention of osteoporosis at an individual level. Estrogen receptor alpha (ER alpha) plays an important role in increasing BMD via mechanical strain and muscle mass is a reflection of the forces the muscle applies to the bone. The aim of this study is to investigate the effect of the interaction between lean tissue mass (LTM) and the ER alpha polymorphisms T--C (PvuII) [dbSNP: rs2234693] and A--G (XbaI) [dbSNP: rs9340799] on BMD in middle-aged and elderly individuals. Subjects were 2209 community-dwelling Japanese men and women, ages 40 to 79 years. ER alpha polymorphisms in the first intron, T--C and A--G were identified and lumbar spine and femoral neck BMD and LTM were measured by dual-energy X-ray absorptiometry. Both T--C and A--G polymorphisms were divided into two genotype groups (TT vs. TC/CC; AA vs. AG/GG). In postmenopausal women, the effect of LTM on femoral neck BMD was significantly larger for those with the TC/CC genotype than for those with the TT genotype for the T--C polymorphism, and larger for those with the AG/GG genotype than for those with the AA genotype for the A--G polymorphism. This gene-LTM interaction was observed at the femoral neck, but not at the lumbar spine. For men and premenopausal women, no gene-LTM interaction was found. In conclusion, there was an interaction between LTM and the ER alpha T--C and A--G polymorphisms with respect to their effect on femoral neck BMD in postmenopausal women and those with the TC/CC and AG/GG genotypes had larger effects of LTM than those with TT and AA genotypes.

To examine real age-related changes in the prevalence of metabolic syndrome, we studied longitudinal changes in the prevalence of metabolic syndrome in a single cohort of individuals. The participants included 112,960 Japanese (70,996 men, 14-94 years and 41,946 women, 17-85 years), who had received annual examinations between 1989 and 2004. Metabolic syndrome was defined according to the Japan Metabolic Syndrome Criteria Study Group and the US National Cholesterol Education Program (NCEP) guidelines. Overweight was defined as BMI>or=25 kg/m(2). Longitudinal changes indicated a birth cohort effect in the prevalence rate of metabolic syndrome with a lower or higher prevalence in the younger birth cohort than in the older for females or males, respectively. The estimation of the age-specific prevalence of metabolic syndrome demonstrated that in males, the prevalence of metabolic syndrome increased up to 50 decades of life for the Japanese and 60 decades of life for the NCEP criteria. In females, the prevalence increased with age up to 80 years old for both criteria. The estimated secular trends suggested that the prevalence rate of metabolic syndrome decreased in females and increased in males during study periods.

To clarify the effectiveness of dietary diversity, calculated by dietary records, on cognitive decline.Data were derived from the National Institute for Longevity Sciences - Longitudinal Study of Aging. Participants comprised 298 men and 272 women aged 60-81 years at baseline (second wave) who participated in the follow-up study (third to seventh wave) at least once. Cognitive function was assessed with the Mini-Mental State Examination in all study waves. Dietary diversity was determined using the Quantitative Index for Dietary Diversity based on a 3-day dietary record in the second wave. Cumulative data among participants with a Mini-Mental State Examination score27 in the second wave were analyzed using a generalized estimating equation. Multivariate adjusted odds ratios and 95% confidence intervals for Mini-Mental State Examination scores ≤27 in each study wave according to a 1 standard deviation (increase), or quartiles of the Quantitative Index for Dietary Diversity at baseline, were adjusted for sex, age, follow-up time, baseline Mini-Mental State Examination score, education, body mass index, annual household income, current smoking status, energy intake and disease history.Multivariate adjusted odds ratio for a decline in Mini-Mental State Examination score was 0.79 (95% CI 0.70-0.89; P 0.001) with a 1 SD increase in dietary diversity score, or 1.00 (reference), 0.99 (95% CI 0.70-1.43), 0.68 (95% CI 0.46-0.99) and 0.56 (95% CI 0.38-0.83) according to the lowest through highest quartiles of dietary diversity score, respectively (trend P = 0.001).Daily intake of various kinds of food might be a protective factor against cognitive decline in community-dwelling Japanese older adults. Geriatr Gerontol Int 2017; 17: 937-944.

Fatty acid-binding proteins (FABP) play a crucial role in intracellular fatty acid transportation and metabolism. In this study, we investigate the effects of the FABP3 Asp3Gly (D3G) polymorphism on protein structure and function. Although the mutation did not alter protein secondary structure or the ability to bind 1-anilinonaphthalene-8-sulfonic acid and palmitate, the intracellular stability of the D3G mutant was significantly decreased. Immunocytochemical analysis reveals that the mutation alters FABP3 subcellular localization. Our results suggest that the D3G polymorphism may impact energy metabolism and physiological functions.

Aim: To study the association between the klotho gene polymorphism and cognitive impairment in community-living men and women. Methods: The subjects consisted of 2234 community-living Japanese men and women aged 40–79 years. The klotho gene promoter polymorphism G-395A was identified and cognitive function was assessed using the Japanese Wechsler Adult Intelligence Scales – Revised Short Forms ( JWAIS-R SF) and Mini-Mental State Examination (MMSE). Brain infarction and atrophy were assessed by brain magnetic resonance imaging (MRI). The differences in cognitive function, infarction and atrophy were compared between the GG type and GA/AA type of the klotho gene G-395A polymorphism. Results: The distribution of the klotho gene G-395A polymorphism was GG 1639 (73.4%), GA 539 (24.1%), and AA 56 (2.5%). There was no significant difference in intelligence quotient (IQ) between the GG type and GA/AA type in the subjects aged 40–59 years. However, the IQ level was significantly different in terms of the klotho genotype for subjects aged 60–79 years (P = 0.004). The mean and SE of IQ levels of the subjects with the GG type and the GA/AA type at nucleotide −395 were 99.8 ± 0.5 and 102.6 ± 0.8, respectively. There were also significant differences in three subtests of JWAIS-R SF – Information, Similarities, and Picture Completion – for subjects aged 60–79 years. Also, the MMSE score was slightly lower for the GG type than for the GA/AA type (P = 0.099). However, there were no differences in the findings of brain MRI. Conclusion: There were statistically significant differences in cognitive function for klotho gene promoter polymorphism G-395A only in subjects aged 60 or over. This polymorphism may be associated with age-related cognitive impairment.

To observe the effect of smoking habit on age-related serum lipid levels, we examined a large cohort of Japanese cross-sectionally and longitudinally. The participants included 103,648 Japanese men and women 17-94 years of age, who had received annual health examinations from 1989 to 2003. In cross-sectional analysis, total and LDL cholesterol levels of smokers were lower than those of nonsmokers up to an elderly age in men and up to middle age in women. Smoking was associated with decreased HDL cholesterol levels up to the 65-74 years age group in men and 55-64 years in women. The triglyceride levels were higher in smokers in both genders than those of nonsmokers below 55-64 years. In the longitudinal analysis, although smoking was associated with lower total and LDL cholesterol up to 60 years of age in women, beyond the sixties an inverted association was observed. The associations of smoking with lower LDL cholesterol levels in men and lower HDL cholesterol in both genders were fairly consistent at any given age. The increase of triglyceride levels in female smokers remained rather constant between 25 and 75 years, whereas the increase in triglyceride levels in male smokers was greater with older ages up to middle age. These results suggest that the effect of smoking on the serum lipid levels is dependent on age and gender.

BACKGROUND: There are few studies about dietary supplement use and nutrient intake from these products in Japan. The purpose of this study was to clarify (1) the prevalence of dietary supplement use, (2) the characteristics of dietary supplement users, (3) nutrient intake from dietary supplements, and (4) the existence of dietary supplement users who took excessive nutrients from these products.METHODS: To collect the information on dietary supplement use in the previous year and nutrient intake from these products, we conducted a self-administered dietary supplement frequency questionnaire. The subjects were 2,259 people aged 40-82 years. Dietary supplements were grouped into 8 major categories. A dietary supplement database was developed to estimate nutrient intake from these products. Excess users were defined as people who consumed more nutrient than the tolerable upper intake level of the Dietary Reference Intakes for Japanese.RESULTS: In the previous year, 55 % of males and 61 % of females consumed dietary supplements. Dietary supplement use was especially prevalent in females, subjects who felt unhealthy, and subjects who were more careful of maintaining an appropriate weight, though the association was affected by the frequency of dietary supplement use. The most common dietary supplements were drink type in males and vitamins in females. Some nutrient values obtained from dietary supplements were higher than those from food. Excess users were found for intake of vitamin A, B6, K, niacin, iron, and magnesium.CONCLUSIONS: It is important to clarify dietary supplement use and to estimate nutrient intake from these products.J Epidemiol 2006; 16: 249-260.

四訂日本食品成分表を用いて算出した栄養素等摂取量推定値 (四訂栄養素摂取量) と, 五訂日本食品成分表を用いて算出した栄養素等摂取量推定値 (五訂栄養素摂取量) とを比較し, 食品成分表改訂が栄養素等摂取量に与える影響を検討した。40-82歳の地域住民2,110名の食物摂取量を3日間食事記録調査により把握し, 四訂栄養素摂取量を算出した。四訂食品番号を五訂食品番号に変換後再計算し, 四訂, 五訂栄養素摂取量の差と関連について検討した。五訂栄養素摂取量から四訂栄養素摂取量を引いた値と, その値が四訂栄養素摂取量に占める割合は, 鉄の-2.1mg (-16%) からカロテンの+1,132μg (+31%) までで, タンパク質, レチノール以外は有意差がみられた。四訂と五訂の栄養素等摂取量の相関は0.934 (カロテン) から0.996 (エネルギー, タンパク質) と高かったが, 回帰分析の結果タンパク質以外は四訂栄養素摂取量と五訂栄養素摂取量に系統的な誤差が存在することが示唆された。

The Japanese have a polymorphism in the alcohol dehydrogenase 2 gene (ADH2). The alleles of ADH2 (ADH2*1 and ADH2*2) encode more active and less active forms for ethanol metabolism, respectively. We examined whether liver damage and the insulin-glucose axis vary according to ADH2 genotype in the Japanese. The 2,232 subjects (1,126 men and 1,106 women) were recruited from a population-based prospective cohort study. Clinical evaluations including alcohol consumption, percentage of alcohol drinkers, plasma glucose, HbA1c, insulin, AST, ALT, gamma-GTP, and prevalence of diabetes were compared among the ADH2 genotypes. The percentage of drinkers, alcohol consumption, AST, ALT, and gamma-GTP were higher in group ADH2*1/1 than in group ADH2*1/2 or ADH2*2/2 (all P0.05). Hence, ADH2*1/1 is associated with excess alcohol intake and liver disorders. However, the prevalence of diabetes did not differ among the three groups. For the glucose-insulin axis, we examined subjects who did not receive insulin therapy or oral anti-diabetes medication. While amounts of alcohol consumed and glucose levels were nearly the same between ADH*1/2 and ADH2*2/2, insulin concentrations were lower in ADH2*2/1 than in ADH2*2/2 (P0.05 in men). This finding suggests that the ADH2*1 allele is associated with a lower insulin concentration when alcohol intake is light or moderate. It also suggests that the genetic effect of ADH2*1 plays an important role in alcohol drinking behavior and in the occurrence of liver injury, but the effect is so mild that it does not influence the glucose-insulin axis or prevalence of diabetes.

Background There has never been a large scale population-based study of serum levels of total testosterone (TT) and free testosterone (FT) in Japanese men. Methods We determined serum levels of TT and FT of 1120 Japanese men aged 40–79 years using radioimmunoassay (RIA), as a part of a population-based longitudinal study of aging. Of these, sex hormone binding protein (SHBG) was also measured by RIA in 471 men. For the latter group, the calculated free testosterone (cFT) was determined by a formula using serum level of albumin, TT and SHBG. Results The mean ± 2 SD of TT, FT and cFT were 513 ± 326 ng/dL (187–839 ng/dL), 13.2 ± 7.8) pg/mL (5.4–21.0 pg/mL) and 77.0 ± 43.4 pg/mL (33.6–120.4 pg/mL), respectively. While TT did not relate to age, FT and cFT decreased with age. FT in the 40–49 years age group was 15.1 ± 8.4 pg/mL (6.7–23.5 pg/mL), in the 50–59 years age group was 13.9 ± 6.8 pg/mL (7.1–20.7 pg/mL), in the 60–69 years age group was 12.0 ± 6.6 pg/mL (5.4–18.6 pg/mL) and in the 70–79 years age group was 11.5 ± 7.0 pg/mL (4.5–18.5 pg/mL). FT significantly correlated with cFT (Spearman's r = 0.803). The correspondence rates were 92.3% at the mean −1 SD and 98.7% at the mean −2 SD level. Conclusions We determined the mean and standard deviation of TT, FT and cFT in Japanese men aged 40 years or older. It is supposed that FT determined by RIA would be useful for diagnosing partial androgen deficiency of aging males.

Aim: The purpose of the present study is to assess the relationships of muscle strength and power with recent leisure-time physical activity and exercise during adolescence in middle-aged and elderly Japanese women. Methods: The subjects consisted of 1128 community-dwelling women aged 40–79 years. They were interviewed about their physical activity habits during leisure time in the past 12 months and exercise they engaged in during adolescence. Muscle function was measured as grip strength, knee extension strength and leg extension power. Subjects were grouped into three intensity levels for leisure-time physical activity and as to whether or not they engaged in adolescent exercise. The relationships of muscle strength and power with leisure-time physical activity and adolescent exercise were assessed using analysis of covariance controlled for age, smoking status, annual income and education level. Results: The proportion of subjects that participated in leisure-time physical activity was 67.1% (light, 33.7%; moderate or heavy, 33.4%). The subjects that engaged in adolescent exercise represented 41.9% of the total. There was a significant relationship between leisure-time physical activity and adolescent exercise. In the analysis of covariance controlled for age, smoking status, annual income and education level, leisure-time physical activity and adolescent exercise had significant main effects on all muscle strength and power measurements. However, there was no interaction effect between leisure-time physical activity and adolescent exercise. Conclusion: The results suggest that current leisure-time physical activity and adolescent exercise benefit muscle function in middle-aged and elderly women.

We examined whether a −34T → C polymorphism of the gene for cytochrome P450, family 17, subfamily A, polypeptide 1 ( CYP17A1 ), a −493G → T polymorphism of the microsomal triglyceride transfer protein gene ( MTP ), and a CGG repeat polymorphism of the very low density lipoprotein receptor gene ( VLDLR ) were associated with bone mineral density (BMD) in community-dwelling Japanese women and men. The −34T → C polymorphism of CYP17A1 was associated with BMD in postmenopausal women, with the CC genotype being related to increased BMD. The −493G → T polymorphism of MTP was associated with BMD in premenopausal women, with the TT genotype being related to increased BMD. The CGG repeat polymorphism of VLDLR was associated with BMD in men, with two (CGG) n ≥ 8 alleles being related to increased BMD. These results suggest that CYP17A1 and MTP are susceptibility loci for increased BMD in postmenopausal and premenopausal Japanese women, respectively, and that VLDLR constitutes such a locus in Japanese men.

To study the effect of aging on astigmatism in adult Japanese. Measurements of refractive errors and keratometry were performed on 2161 randomly selected subjects (aged 40–79 years). The relation between age and the net value in diopters (D) of astigmatism was evaluated with a trend test. The relation between age and the polar value was also examined by linear regression analysis. The mean (±SD) value of total and corneal astigmatism was −0.97 ± 0.72 D and −0.86 ± 0.63 D, respectively, and the net value of both increased with age (P trend < 0.001). The prevalence of either type of astigmatism also increased with age, according to the Cochran-Mantel-Haenzel test (P < 0.0001 for total and P < 0.01 for corneal astigmatism). The prevalence of against-the-rule astigmatism increased with age for either type of astigmatism (P < 0.0001 for total, P < 0.0001 for corneal). According to the analysis of polar values by age, the regression coefficient (±SE) for total and corneal astigmatism was −0.024 ± 0.002 (P < 0.0001) and −0.028 ± 0.002 (P < 0.0001), respectively. There was no statistical difference between these two regression coefficients. The prevalence of astigmatism increases and the axis turns to against-the-rule with age. The result of the linear regression analysis indicates that the age-related change in astigmatism is mainly associated with changes in the cornea.

The purpose of this longitudinal study was to examine the moderating effects of age and social support from family members in the relationship between the bereavement of friends and depression. The participants were 1 402 Japanese community-dwelling men and women aged between 40 and 79 years, who had done the baseline and the two-year follow-up surveys of the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA). By using hierarchical multiple regression analysis, we detected a significant interaction between age, social support from family members, and the bereavement of friends. Younger participants who were receiving less support from family members after the loss of friends showed significantly higher depression scores.

Genetic variants of the androgen receptor and klotho protein may contribute to variation in bone mass as well as to predisposition to osteoporosis. The relationship of a CAG repeat polymorphism of the androgen receptor gene (AR) and of a -395G--A polymorphism of the klotho gene (KL) to bone mineral density (BMD) in Japanese women was examined in a population-based study. The subjects (1,101 and 1,110 women for AR and KL polymorphisms, respectively) were aged 40-79 years and were randomly recruited to a population-based prospective cohort study of aging and age-related diseases. BMD for the total body, lumbar spine, right femoral neck, right trochanter, and right Ward's triangle was measured by dual-energy X-ray absorptiometry. Genotypes for the AR and KL polymorphisms were determined by polymerase chain reaction based assays. The number of CAG repeats of AR was inversely correlated with BMD for the lumbar spine in premenopausal women but not in postmenopausal women. The (CAG)(n/=22) and (CAG)(n/=23) alleles were designated S and L, respectively. Among premenopausal women, BMD for the total body was significantly lower in subjects with the LL genotype than in those with the SS genotype or those in the combined group of SS and SL genotypes. In contrast, BMD was not associated with AR genotype in postmenopausal women. Among all women, BMD for the lumbar spine was significantly lower in subjects with the GG genotype of the -395G--A polymorphism of KL than in those with the AA genotype. BMD was not associated with -395G--A genotype among premenopausal women. In postmenopausal women, BMD for the total body or lumbar spine tended to be lower in subjects with the GG genotype than in those with the AA genotype or those in the combined group of GA and AA genotypes. These results suggest that AR is a susceptibility gene for reduced BMD in premenopausal Japanese women, and that KL is a susceptibility gene for reduced BMD in all women.

The current study was conducted to investigate the cognitive function in Japanese elderly with type 2 diabetes mellitus (DM). Participants included 69 diabetic and 27 nondiabetic subjects (60 to 85 years old). The cognitive functional tests conducted were the Mini-Mental State Examination (MMSE), Word Lists Recall (immediate, delayed), Digit Symbol Test (Wechsler Adult Intelligence Scale-Revised [WAIS-R]), and the Stroop Color Word Test. Hemoglobin A1c (HbA1c) was measured as the index of glycemic control, and information about recent hypoglycemic episodes was gathered by using questionnaires. Student's t test showed that DM subjects had significantly lower scores in the MMSE (P

This study examined associations between physical activity and depressive symptoms in 1,151 community-dwelling adults in Japan. Physical activity was measured using a pedometer, whereas depressive symptoms were assessed with the Center for Epidemiological Studies-Depression Scale. A structural equation modeling with a cross-lagged panel design revealed that for the older adults (65-79 years of age), daily walking at baseline predicted fewer depressive symptoms at the 2-year follow-up, even after adjusting for confounders. In contrast, the association was not confirmed for the middle-aged adults (40-64 years of age). Findings suggest that age should be considered when estimating the effect of physical activity on psychological well-being.

The aim of this study was to describe the distribution of visual acuity and investigate the predictors of visual impairment in a Japanese population. Best-corrected visual acuity was measured in 2263 subjects aged 40–79 years randomly selected from a local community. Relations between visual impairment and possible risk factors were investigated. Among these subjects, 41 individuals (1.8%) were identified as visually impaired (best-corrected visual acuity in the better eye ≪0.5). Both sexes in the older age groups had a higher frequency of visual impairment (Mantel-Haenszel chi-square test: P ≪ 0.001). A multiple logistic regression indicated that an increase in age of 10 years [odds ratio (OR) 3.9; 95% confidence interval (CI) 2.3–6.7] and myopia (OR 2.9; 95%CI 1.4–6.0) were independent risk factors for visual impairment. Individuals with the highest level of education (college or higher) had a lower risk of visual impairment (OR 0.1; 95%CI 0–0.7) compared to individuals with the lowest level of education. As expected, visual impairment increased with advancing age, although the prevalence of visual impairment in our population was lower than in other surveys. Racial and regional differences and differences in study design may be responsible for discrepancies between surveys. It is noteworthy that myopia was a significant risk factor for visual impairment, although the reasons for this association are uncertain and need further investigation. Jpn J Ophthalmol 2004;48:37–43 © Japanese Ophthalmological Society 2004

To validate the Clock Drawing Test (CDT) as a screening method for detecting mild cognitive impairment (MCI) and to find the appropriate scoring protocol and its cutoff point, we compared the sensitivity and specificity of three CDT protocols. Subjects included 219 outpatients with memory complaints, who were attending the geriatric memory clinic. Cahn’s protocol, with a cutoff point of 7, was more successful at differentiating clinically diagnosed MCI subjects from normal elderly individuals, with higher sensitivity (74.7%) and specificity (75.6%), than were the other protocols. The CDT, as a handy screening method, may be useful for clinicians to reliably identify subjects with MCI, and it may contribute to early detection of dementia.

A -521C--T polymorphism in the promoter of the dopamine receptor D4 gene (DRD4) has been associated with novelty-seeking behavior in Japanese. Given that the dopaminergic system might also play an important role in bone metabolism, the relation of the -521C--T polymorphism of DRD4 to bone mineral density (BMD) was examined in 2,228 Japanese subjects (1,123 men; 1,105 women) who were randomly recruited to a population-based, prospective cohort study. BMD at the radius was measured by peripheral quantitative computed tomography, and that for the total body, lumbar spine, right femoral neck, right trochanter, and right Ward's triangle was measured by dual-energy X-ray absorptiometry. Genotype was determined with a fluorescence-based allele-specific DNA primer assay system. For men, BMD for the distal radius, total body, lumbar spine, trochanter, or Ward's triangle was lower in individuals with the CC genotype than in the combined group of TT and TC genotypes or in those with the TT genotype or with the TC genotype. The urinary concentration of deoxypyridinoline was slightly, but significantly, greater in men with the CC genotype than in those with the TT or TC genotypes or with the TT genotype. For women, there were no differences in BMD among -521C--T genotypes. These results implicate DRD4 as a candidate locus for reduced BMD in Japanese men.

Given that osteoprotegerin plays an important role in bone remodeling, the osteoprotegerin gene may be a candidate locus for susceptibility to osteoporosis. The relation of polymorphisms in the promoter of the osteoprotegerin gene to bone mineral density (BMD) was examined in a Japanese population-based prospective cohort study with randomly recruited subjects (1095 women and 1125 men for the 950T --> C polymorphism, 1094 women and 1127 men for the 245T --> G polymorphism). BMD at the radius was measured by peripheral quantitative computed tomography, and that for the total body, lumbar spine, right femoral neck, right trochanter, and right Ward's triangle was measured by dual-energy X-ray absorptiometry. Genotypes were determined with a fluorescence-based allele-specific DNA primer assay system. Among 950T --> C genotypes, BMD for the proximal radius was lower in premenopausal women with the CC genotype than in those with the TT or TC genotype; the difference in BMD between the two groups was 3.9% (P=0.0075). Among 245T --> G genotypes, BMD for the radius, total body, femoral neck, trochanter, and Ward's triangle was lower in postmenopausal women with the GG genotype than in those with the TT or TG genotype, the TT genotype, or the TG genotype; the differences in BMD between the GG genotype and the TT or TG genotype were 19.8% for the distal radius (P=0.0015), 13.1% for the proximal radius (P=0.0095), 11.2% for the total body (P=0.0013), 12.9% for the femoral neck (P=0.0067), 18.7% for the trochanter (P=0.0008), and 27.1% for Ward's triangle (P=0.0038). BMD was not associated with the 950T --> C or 245T --> G genotypes in men. The present results implicate the osteoprotegerin gene as a susceptibility locus for reduced BMD in Japanese women.

Although polymorphism of the mitochondrial DNA 15497guanine/adenine (Mt15497G-->A) leads to the Gly251Ser amino acid replacement on human cytochrome b, it is unknown whether functional alteration of the mitochondrion is induced by the Gly251Ser replacement. To see if an association exists between the Mt15497G-->A polymorphism and obesity, we examined differences in body size, body composition, and regional body fat distribution between the two genotypes in middle-aged and elderly Japanese individuals (825 women and 906 men). The Mt15497 genotype was determined with an automated colorimetric allele-specific DNA probe assay system using the polymerase chain reaction (PCR) method. The Mt15497G-->A polymorphism was detected in 3.5% ( n=60) of all subjects: 2.8% ( n=23) among women and 4.1% ( n=37) among men. After adjusting for age and smoking, we found that body weight, body mass index, waist and hip circumferences, fat mass, fat-free mass, intra-abdominal fat and triglycerides were significantly greater in women with the A allele compared with the G allele ( p=0.001-0.025). For men, waist to hip ratio was significantly greater ( p=0.032), and waist circumference, intra-abdominal fat and triglycerides had a trend to be significantly greater ( p=0.062-0.087) in subjects with the A allele compared with the G allele. These data suggest that the Mt15497 polymorphism may be associated with obesity-related variables and lipid metabolism.

Background: The purpose of the present paper was to examine the differences in the levels of hematological or biochemical parameters among elderly hospital patients, nursing home residents, and mass health check-up recipients. Methods: One hundred and 44 geriatric inpatients (aged ≥ 65 years), 237 outpatients, 146 nursing home residents, 120 aged examinees from mass health check-ups, and 512 younger health check-up examinees (controls) were included in the present study. They were divided into five male and five female subgroups, respectively. The levels of hemoglobin (Hb), white blood cells (WBC), serum albumin (Alb), Ca, albumin-corrected Ca, Na, creatinine (Cr), and total cholesterol (TC) were determined and compared. Results: There were significantly lower levels of Hb, Alb, Ca, Na, and TC in inpatients than in other groups in both sexes. In contrast, higher levels of WBC and Cr were found in inpatients. Among women there was no difference in the level of any parameter between nursing home residents, health check-up examinees, and controls. Conclusion: The data indicate that the levels of these parameters are affected to a greater extent in inpatients, and that female nursing home residents and health check-up examinees show values similar to those of controls.

Magnesium (Mg) deficiency is believed to have adverse cardiovascular consequences that are broad and complex, although an association between dietary Mg intake and the risk of coronary heart disease (CHD) has not been clearly identified. The purpose of this study is to examine the relation between dietary Mg intake and future risk of CHD. Reported findings are based on dietary Mg intake in 7,172 men in the Honolulu Heart Program. Intake of Mg was recorded at baseline examinations that took place from 1965 to 1968 when the men were aged 45 to 68 years. In 30 years of follow-up, 1,431 incident cases of CHD were identified. Within 15 years after dietary assessment, the age-adjusted incidence decreased significantly from 7.3 to 4.0 per 1,000 person-years in the lowest (50.3 to 186 mg/day) versus highest (340 to 1,183 mg/day) quintiles of Mg intake (p

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) plays a major role in acetaldehyde detoxification. The alcohol sensitivity is associated with a genetic deficiency of ALDH2. We and others have previously reported that such a deficiency influences the risk for late-onset Alzheimer's disease (LOAD), hypertension, and myocardial infarction. Then we tried to find phenotypes to which the ALDH2 polymorphism contributes by conducting several evaluations including biochemical and functional analyses of various tissues in a community-dwelling population. Several serum proteins, lipids, and lipid peroxides (LPO) levels showed differences between the nondefective (ALDH2*1/1) and defective (ALDH2*1/2 and ALDH2*2/2) ALDH2 individuals. However, alcohol-drinking behavior is known to affect these evaluations. Thus, we excluded the effects of alcohol-drinking behavior from the association with the ALDH2-deficient genotype through correction and found that the concentration of LPO was significantly lower in the nondefective ALDH2 females than the defective females. The effect of frequent alcohol-drinking behavior in males seems to override the phenotype of the high serum LPO level. These results indicate that the ALDH2 deficiency may enhance oxidative stress in vivo. Thus, these findings suggest that ALDH2 functions as a protector against oxidative stress and the decrease in protection may influence the onset of AD, hypertension, and myocardial infarction.

We examined whether the −634C→G, 298C→T, and 2C→T polymorphisms of the IL-6, osteocalcin, and vitamin D receptor (VDR) genes, respectively, were associated, alone or in combination, with bone mineral density (BMD) in community-dwelling Japanese women (between 1108 and 1113) or men (between 1116 and 1130) aged 40–79 yr. The −634C→G polymorphism of the IL-6 gene and the 298C→T polymorphism of the osteocalcin gene were associated with BMD in postmenopausal women, with the respective GG and TT genotypes representing risk factors for reduced bone mass. IL-6 and osteocalcin genotypes showed additive effects on BMD for postmenopausal women. The 2C→T polymorphism of the VDR gene was associated with BMD in men, with the CT genotype contributing to reduced BMD. These results suggest that the IL-6 and osteocalcin genes are susceptibility loci for reduced BMD in postmenopausal women and that the VDR gene constitutes such a locus in men. The combined IL-6 and osteocalcin genotypes may prove informative for the assessment of osteoporosis in women.

Background: To reduce the length of stay (LOS) in hospital, the factors associated with extended LOS have to be identified. Methods: A comprehensive geriatric assessment (CGA) of patients in a geriatric ward was carried out to identify the factors associated with LOS of more than 28 days. Results: Of 193 patients (> 65 years old) who had been admitted to the geriatric ward of Nagoya University Hospital from home, 118 patients had complete CGA data sets. The CGA items were studied within 1 week of admission and analysis was performed by Chi-squared followed by multilogistic analysis. Chi-squared analysis demonstrated that many of the basic activities of daily living (BADL) and instrumental ADL (IADL) had a significant association with longer LOS, but the contribution of psychological factors, assessed by mini-mental state examination and Geriatric Depression Scale-15, was relatively small. Multilogistic analysis showed that dependence on dressing assistance and medication assistance significantly increased the chance of having a LOS longer than 28 days. Conclusion: Intervention to improve the ability to dress and take medication independently may reduce LOS.