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BACKGROUND/OBJECTIVES To clarify the effects of intake of legumes and isoflavones on all-cause mortality in middle-aged and older Japanese. SUBJECT/METHODS The subjects were 2136 randomly chosen community-dwelling Japanese men and women aged 40-79 years who participated in a first-wave survey (1997-2000; baseline). The subjects were followed from baseline to December 31, 2017 (mean period of 16.6 ± 4.2 years). Intake of legumes, soybeans, and isoflavones at baseline was assessed using a 3-day dietary record with photographs. The relationships of intake amounts of legumes and isoflavones to mortality were assessed using Cox proportional hazards regression controlling for age, sex, education, employment, body mass index, smoking habits, medical histories, drinking, and energy intake. RESULTS There were 491 deaths during the follow-up period. We found inverse associations of the intake of total soy products and intake of each of the isoflavones with all-cause mortality (p for trend

Background The gap between the average life expectancy and healthy life expectancy remains wide. Understanding the natural history of frailty development is necessary to prevent and treat frailty to overcome this gap. This study elucidated the trajectories of 5 frailty assessment components using group-based multitrajectory modeling. Methods Overall, 845 community-dwelling older adults (aged 65–91 years; 433 males and 412 females) who underwent longitudinal frailty assessments at least 3 times were included in the analysis. The mean follow-up period (±SD, range) was 7.1 (±2.3, 3.8–11.3) years. In each wave, the physical frailty was assessed for the following 5 partially modified components of the Cardiovascular Health Study criteria: shrinking, weakness, exhaustion, slowness, and low activity. Using group-based multitrajectory modeling, we identified subgroups that followed distinctive trajectories regarding the 5 frailty components. Results Five frailty trajectory groups were identified: weakness-focused frail progression group (Group 1 [G1]; 10.9%), robust maintenance group (Group 2 [G2]; 43.7%), exhaustion-focused prefrail group (Group 3 [G3]; 24.3%), frail progression group (Group 4 [G4]; 6.7%), and low activity–focused prefrail group (Group 5 [G5]; 14.4%). The Cox proportional hazards model analysis showed that G1, G4, and G5 had significantly higher mortality risks after adjusting for sex and age (G2 was the reference group). Conclusion Based on the natural history of frailty, the 5 distinctive trajectory groups showed that some individuals remained robust, while others remained predominantly prefrail or progressed primarily owing to physical mobility decline. Therefore, identifying individuals belonging to these progressive frailty groups and providing interventions according to the characteristics of each group may be beneficial.

We investigated the associations between hearing aids (HA) and the maintenance of cognitive function among community-dwelling older adults with moderate hearing loss. A total of 407 participants aged 60 years or older with moderate hearing loss were recruited from the National Institute for Longevity Sciences, Longitudinal Study for Aging (NILS-LSA). Moderate hearing loss was defined as a pure-tone average of 40–69 dB at 500, 1000, 2000, and 4000 Hz of the better ear, according to the definition proposed by the Japan Audiological Society. Cognitive function was evaluated using the four subtests of the Japanese version of the Wechsler Adult Intelligence Scale-Revised Short Forms (WAIS-R-SF): Information, Similarities, Picture completion, and Digit Symbol Substitution (DSST). A longitudinal analysis of 1192 observations with a mean follow-up period of 4.5 ± 3.9 years was performed. The HA use rate at any time during the follow-up period was 31.4%, and HA users were significantly younger (t-test, p = 0.001), had worse hearing (p < .0001) and higher education (p = 0.001), participated more frequently in the survey (p < .0001), and were less depressed (χ2 test, p = 0.003) than the older adults not using HA. General linear mixed models consisted of the fixed effects of HA use, follow-up time, and an HA use × time interaction term adjusted for age and pure-tone average thresholds at baseline, sex, education, and other possible confounders. HA use showed significant main effects on the scores for Picture completion and DSST after adjustment; scores were better in the HA use group than in the no HA use group. The HA use × time interaction was significant for the Information score (p = 0.040). The model-predicted 12-year slope with centralizing age indicated that the no HA use group showed greater decline over time on Information scores than did HA use group. The slopes did not differ between HA users and non-users for the Similarities, Picture completion and DSST. In conclusion, HA use may have a protective effect on the decline in general knowledge in older adults with moderate hearing loss.

Background There is a growing interest in the significance of adopting a variety of lifestyle habits for maintaining cognitive function among older adults. A lifestyle that is easy to modify, simple, and less burdensome for older people is ideal. We investigated the longitudinal association between global cognitive decline and cognitive leisure activities (CLAs) combined with long-chain polyunsaturated fatty acids (LCPUFAs) intake. Methods The National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) enrolled community-dwelling middle-aged and older men and women who were randomly selected from Obu-City and Higashiura Town, Aichi, Japan. Baseline data (2006–2008), including CLAs and dietary intake, were obtained from 517 participants (aged 60–84 years) with normal cognition. Global cognitive decline, defined as the Mini-Mental State Examination (MMSE) score ≤ 27, was assessed at baseline and four years later. Interaction between CLAs and LCPUFAs on cognitive decline was investigated using a multiple logistic analysis with adjustment for confounders. CLA engagement and LCPUFA intake were divided into high and low groups according to the frequency at which each participant engaged in the activity and the median intake level according to sex, respectively. Results A significant interaction was detected for the combination of CLA engagement and LCPUFA intake. Logistic regression coefficients revealed significant interactions when participants engaged in more than five CLA varieties. One of the CLAs, art appreciation, produced a significant main effect against cognitive decline and a significant interaction in combination with LCPUFA intake. The major LCPUFAs—docosahexaenoic acid and arachidonic acid—also exhibited a significant interaction. The combination of high LCPUFA intake and high art appreciation frequency yielded a lower adjusted odds ratio for cognitive decline than the combination of low LCPUFA and low art appreciation [0.25 (95 % confidence intervals, 0.11–0.56)]. Conclusions Preserving cognitive function might be associated with a combination of varied and high-frequency engagement in CLAs combined with high LCPUFA intake.

Objective:To examine the association between green tea and coffee intake and cognitive decline in older adults.Design:A prospective cohort study. The average intake of green tea and coffee in the previous year was assessed through a dietitian interview using a dietary questionnaire. A Mini-Mental State Examination (MMSE) was conducted up to six times biennially. Cognitive decline was screened using the MMSE; its incidence was defined as the first time a score of Setting:The National Institute for Longevity Sciences, Longitudinal Study of Aging (NILS-LSA) in Japan.Participants:Men (n 620) and women (n 685), aged 60–85 years, from the NILS-LSA.Results:During a mean of 5·3 (sd 2·9) years of follow-up, 432 incident cases of cognitive decline were observed. Compared with participants who consumed green tea Ptrend < 0·05). No significant association was found between coffee intake and cognitive decline.Conclusions:The intake of green tea, but not coffee, was shown to reduce the risk of cognitive decline in older adults.

This study examined the association between frailty development and physical activity including the number of steps, the time of light-intensity physical activity (LPA) with3.0 metabolic equivalents (METs), and the time of moderate- to vigorous-intensity physical activity (MVPA) with ≥3.0 METs in community-dwelling older Japanese adults.Study subjects were 401 older adults at the baseline examination (April 2000-May 2002) who participated at least once in the follow-up examination of the longitudinal study of aging. Their 1787 cumulative data points (mean number of repeat visits, 3.5) were used for analysis.The number of steps, time of LPA, and time of MVPA were recorded at baseline using a uniaxial accelerometer. Frailty was defined according to 5 frailty criteria: shrinking, exhaustion, low physical activity, low grip strength, and slow gait speed.The fully adjusted odds ratio for frailty among subjects walking5000 steps was 1.85 [95% confidence interval (CI), 1.10-3.11]. The fully adjusted odds ratio for frailty among subjects with MVPA for7.5 minutes was 1.80 (95% CI, 1.05-3.09). No significant association was observed between frailty and LPA.The risk for developing frailty was substantially lower in older people walking ≥5000 steps/d or exercising for at least 7.5 minutes/d at an intensity3.0 METs. These data could be applicable to the community interventions that aim to prevent frailty.

Background Hyperglycemia is believed to be a risk factor for cognitive decline, but the longitudinal relationship between hyperglycemia and cognitive decline in the Japanese population is unclear. The present study aimed to clarify the association between blood glucose levels and information processing ability in middle-aged and older adults. Methods The subjects were 866 men and 815 women aged 40–79 years not taking medication for diabetes who participated in the first study wave (1997–2000) and then participated at least once in the subsequent six study waves (2000–2012) of the National Institute for Longevity Sciences—Longitudinal Study of Aging, Japan. Hemoglobin A1c (HbA1c) levels were categorized into four groups (

The brain controls human behavior, and the gray matter is the main resource of neuronal cells. We examined the longitudinal relationship between six basic lifestyle habits (diet, exercise, sleep, alcohol consumption, smoking, and social activity including employment) and total gray matter volume in community-dwelling adults in Japan. This two-year follow-up study with data derived from the National Institute for Longevity Sciences, Longitudinal Study of Aging, Aichi, Japan, included adults aged 40-87 years (n = 1665, men: 51%). Lifestyle habits were assessed at baseline (2008-2010) using self-reported questionnaires and three-day dietary records. Total gray matter volume at baseline and after two years was estimated using T1-weighted brain magnetic resonance imaging and FreeSurfer software. The association between each lifestyle factor, the total number of healthy lifestyle habits, and gray matter volume change was determined via a multiple linear regression analysis adjusting for baseline age, total gray matter volume, and other confounders. The mean ± standard deviation decrease in total gray matter volume during the two-year follow-up period was 0.94 ± 1.86% in men and 0.61 ± 2.27% in women. In the multiple regression analysis, volume loss in total gray matter positively correlated with male smoking, while it was negatively correlated with male social activity and employment, female dietary diversity, and the total number of healthy lifestyle habits (standardized beta coefficient; -0.061 in men [p = 0.07], -0.113 in women [p 0.05]). Therefore, engaging in social activities, non-smoking, a diverse diet, or adopting one healthy lifestyle habit may help prevent gray matter volume loss.

Background To investigate the association between green tea consumption and the annual rate of change of gray matter (GM), white matter (WM), and hippocampal volumes in community-dwelling middle-aged and older Japanese individuals. Methods A prospective cohort study with two years of follow-up was conducted as part of the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) project. A total of 1693 participants (862 men and 831 women, aged 40–89 years) were included. Green tea consumption (mL/day) data were collected with a 3-day dietary record. Volumes of GM, WM, and the hippocampus were estimated by T1-weighted brain magnetic resonance imaging and FreeSurfer software. The GM ratio, WM ratio, and hippocampal ratio (HR) were calculated as the percentages of total intracranial volume, respectively. Results The mean (SD) annual rate of change of hippocampal volume [(HR at baseline - HR at follow-up)/HR at baseline/follow-up years×100%] was 0.499 (1.128) (%). In the multivariable-adjusted general linear model, green tea consumption was negatively associated only with the annual rate of change of hippocampal volume (%) [β (95% CI) for each 1 mL/day increase in green tea consumption = -20.2E-5 (-35.0E-5 to -5.3E-5); P-value = 0.008]. No associations were observed for the annual rate of change of GM or WM volumes. The results remained significant when the analysis was limited to those with stable green tea consumption and were especially evident among individuals aged 65 years and older and among women. Conclusions In this study, higher green tea consumption was associated with less annual hippocampal atrophy, and each additional 100 mL/day of green tea intake was related to a reduction of approximately 5% in annual hippocampal atrophy. This association was especially evident among older individuals and among women. Further study in different settings is needed to confirm this association.

Hearing loss is a risk factor for cognitive impairment, and the use of a hearing aid (HA) may prevent cognitive decline alongside hearing loss. We aimed to elucidate the prevalence of self-reported HA usage in Japanese community-dwelling elders with hearing loss, and the effect of hearing and HA on cognitive impairment.A total of 1193 participants, who had audiometric defined hearing loss and were aged 60 years or over, had their cumulative 3260 observations followed up for 10 years from a large cohort of a Japanese study. Association between hearing (pure-tone average threshold level at 500, 1000, 2000, and 4000 Hz from the better hearing ear: PTABHE) and HA usage with cognitive impairment (total score of Mini-Mental State Estimation was under 27 or diagnosed as dementia) was analyzed using generalized estimating equations.The HA usage rate of the 1193 community-dwelling elders with hearing loss was 6% during the first involvement. The majority (59.2%) of HA users always used an HA. HA usage rate was 0.7% for the mild hearing loss group and 32.4% for the moderate or greater hearing loss group in the latest participating wave. PTABHE was significantly associated with cognitive impairment (odds ratio for every 10 dB 1.36; 95% CI 1.21-1.53, p0.0001) after adjusting for age, sex, education, depressed mood, smoking status, alcohol intake, income, activity, obesity, histories of hypertension, dyslipidemia, ischemic heart disease, diabetes, stroke, ear disease, and occupational noise exposure. PTABHE was also significantly associated with cognitive impairment in the mild hearing loss group (odds ratio for every 10 dB 1.34; 95% CI 1.05-1.72, p = 0.020) and moderate hearing loss group (odds ratio for every 10 dB 1.82; 95% CI 1.27-2.61, p = 0.001). HA use showed a significant suppressive effect on cognitive impairment in those with moderate hearing loss who always use an HA (odds ratio 0.54; 95% CI 0.30-1.00, p = 0.049).The prevalence of HA usage among Japanese community-dwelling elders with hearing loss is consistent, at around 10%. The hearing level remained a primary risk factor for cognitive impairment among elders with hearing loss after adjusting for several confounding factors. Regular HA use may have a protective effect on cognitive impairment in those with moderate hearing loss.

Background: Muscle mass is often mentioned not to reflect muscle strength. For muscle mass assessment skeletal muscle index (SMI) is often used. We have reported that dual-energy X-ray absorptiometry (DXA)-derived SMI does not change with age in women, whereas the cross-sectional muscle area (CSMA) derived from computed tomography (CT) does. Objectives: The present study aimed to compare CT and DXA for the assessment of muscle tissue. Design & Setting: Cross-sectional study in the local residents. Participants: A total of 1818 subjects (age 40-89 years) randomly selected from community dwellers underwent CT examination of the right mid-thigh to measure the cross-sectional muscle area (CSMA). Skeletal muscle mass (SMM) was measured by DXA. The subjects performed physical function tests such as grip strength, knee extension strength, leg extension strength, and gait speed. The correlation between CT-derived CSMA and DXA-derived SMM along with their association with physical function was examined. Results: After controlling for related factors, the partial correlation coefficient of muscle cross-sectional area (CSA) with physical function was larger than that of DXA-derived SMM for gait speed in men (p=0.002) and knee extension strength in women (p=0.03). The partial correlation coefficient of quadriceps (Qc) CSA with physical function was larger than that of DXA-derived SMM for leg extension power in both sexes (p=0.01), gait speed in men (p

We examined associations between dietary diversity and all-cause and cause-specific mortality in 386 men and 413 women (age range, 60&ndash, 79 years at baseline) who took part in the National Institute for Longevity Sciences-Longitudinal Study of Aging study from 1997 to 2000. Dietary intake was assessed using three-day dietary records and photographs. The Quantitative Index for Dietary Diversity was used to determine the dietary diversity among thirteen food groups. Dietary diversity score and each food intake were examined by sex-stratified tertiles, and hazard ratios (HR) were calculated to compare the risk for all-cause and cause-specific deaths across tertiles, after controlling for age, sex, body mass index, alcohol intake, smoking status, education, physical activity, and disease history. During a mean follow-up of 15.7 years, 289 subjects (36.2%) died. Compared to the subjects in the lowest tertile, the multivariate-adjusted HR for all-cause and cancer mortality was 0.69 (95% confidence interval (CI): 0.51&ndash, 0.94) and 0.57 (95% CI: 0.33&ndash, 0.98), respectively (trend p &lt, 0.05), in subjects in the highest tertile of dietary diversity. There were no significant associations between dietary diversity score and death from cardiovascular or cerebrovascular disease. Eating a variety of foods might contribute to longevity in older Japanese community dwellers.

Nutrition plays an important role in the development of frailty, and the present study examined the association between energy, macronutrient, and food intake and the development of physical frailty. Prospective cohort study. The National Institute for Longevity Sciences — Longitudinal Study of Aging (NILS-LSA), a community-based study. Participants included 166 men and 117 women aged 65–86 years without frailty components at baseline who participated in both the sixth (2008–2010) and seventh (2010–2012) waves of the NILS-LSA. Physical frailty was assessed using the modified criteria established by the Cardiovascular Health Study (2001). All participants were classified as “robust (number of frailty components: 0),” “prefrail (1–2),” or “frail (3–5).” Energy, macronutrient, and food intake was calculated based on 3-day dietary records during the sixth wave. Associations between dietary intake per day and the development of frailty 2 years later (from robust at the sixth wave to prefrail/frail at the seventh wave) were examined using multiple logistic regression analysis after adjusting for sex, baseline age, and other covariables. Among the participants included, 36% were classified as prefrail/frail 2 years later. Higher energy [1 standard deviation (SD), odds ratio (95% confidence interval): 362 kcal, 0.68 (0.49–0.94)], protein [16 g, 0.72 (0.53–0.97)], and fat [15 g, 0.69 (0.52–0.92)] intake was negatively associated with frailty development. Higher meat [38 g, 0.68 (0.51–0.92)] and dairy [114 g, 0.73 (0.55–0.96)] intake was negatively associated with frailty development. Higher energy intake was negatively associated with the development of weakness (low grip strength) and low activity, while higher protein intake was negatively associated with the development of low activity. Increased consumption of meat and dairy products may provide sufficient protein and fat necessary for achieving higher energy intake, thereby effectively preventing physical frailty among older Japanese individuals.

Objectives The pathology of sudden sensorineural hearing loss, which is known as sudden deafness (SD), remains unknown. The purpose of this study was to investigate the association between mitochondrial uncoupling protein 2 (UCP2) polymorphism and SD risk. Materials and methods We compared 83 patients suffering from SD and 2048 controls who participated in the Longitudinal Study of Aging at the National Institute for Longevity Sciences. Multiple logistic regression was used to calculate the odds ratios (ORs) for SD with a polymorphism of the UCP2 (rs660339) gene. Results Under the additive model of inheritance, UCP2 polymorphisms showed significant association with a SD risk. The OR was 1.468 (95% confidence interval, 1.056-2.040) with an adjustment for any past history, such as diabetes, dyslipidemia, or hypertension, and for age and sex. Conclusion Our results imply that the UCP2 (rs660339) polymorphism has a significant association with the risk of developing SD.

Data were derived from the National Institute for Longevity Sciences-Longitudinal Study of Aging. Subjects comprised 403 men and 373 women aged 60-81 years at baseline who participated in the follow-up study at least once. Bean, soy product and soy isoflavone intake was assessed using a 3-day dietary record at baseline. Cognitive function was assessed by the Mini-Mental State Examination (MMSE). MMSE scores of ≤23 were used to define cognitive impairment. The relationship between bean, soy product and soy isoflavone intake and cognitive impairment was assessed using a generalized estimating equation. Multivariate-adjusted odds ratios (95% confidence intervals) for cognitive impairment with a 1 s.d. increase in total bean, total soybean and total soy isoflavone intakes were 0.48 (0.28-0.81; p = 0.006), 0.51 (0.32-0.83; p = 0.007), and 0.55 (0.32-0.93; p = 0.026), respectively, in women. Total soybean and soy isoflavone intake might decrease the risk of cognitive impairment in elderly Japanese women.

Background Age-related declines in skeletal muscle mass and strength, representing “sarcopenia,” are a growing concern in aging societies. However, the prevalence of low muscle mass based on the height2-adjustment has been shown to be extremely low, and a more appropriate definition of low muscle mass is needed, particularly for Asian women. The aim of this study was to explore the most appropriate adjustment of appendicular lean mass (ALM) for predicting mortality or disability risk using ALM or any of 5 adjustments of ALM among community-dwelling Japanese. Methods Subjects comprised 1026 men and 952 women between 40 and 79 years old at baseline (1997–2000) who participated in the National Institute for Longevity Sciences - Longitudinal Study of Aging, Japan. ALM (kg) and 5 adjusted indices of ALM (ALM/leg length, ALM/height, ALM/height2, ALM/weight, and ALM/body mass index [BMI]) were assessed at baseline. Disability was defined by long-term care insurance certification based on responses to a survey mailed in 2013, and death records were obtained as vital statistics until December 2014. Crude and adjusted Cox proportional hazard models were used to estimate hazard ratios for mortality or disability by sex-stratified quintiles of each ALM index (ALM and adjusted ALM) or sarcopenia-related indices. The area under the curve (AUC) was calculated with the multivariate-adjusted logistic regression model. Additionally, mixed-effects analyses were used to clarify the age-related ALM indices decline over 12 years (n = 1838). Results Crude Cox proportional hazard models and multivariate-adjusted logistic model (AUC) indicated that higher ALM and ALM/BMI in women, and higher ALM, ALM/leg length, ALM/height, and ALM/BMI in men were associated with lower risks for mortality or disability than ALM/height2. The mixed effect model indicated all ALM indices in men, and ALM, ALM/leg length, and ALM/height in women could better predict age-related lean muscle mass decline. Conclusions Unadjusted ALM in women, and ALM/leg length, ALM/height, ALM/BMI, and ALM in men may be more appropriate for predicting future mortality or disability than ALM/height2. Considering the age-related muscle mass decline, unadjusted ALM would be the first variable to assess, regardless of sex, in this Japanese cohort study. Electronic supplementary material The online version of this article (10.1186/s12877-017-0699-6) contains supplementary material, which is available to authorized users.

Positive and negative associations with risk of cognitive decline have been reported for glycated hemoglobin (HbA1c) level and green tea (GT) intake, respectively. This study aimed to assess whether the reduction in the risk of cognitive decline with GT intake depended on HbA1c level. The participants were aged ≥60 years at baseline in the cohort study, wherein examinations were conducted biennially from 2000 to 2012. Subjects (n=1,304) who had no cognitive decline during the first survey and who had participated in the follow-up survey at least once were included. The follow-up end point was the first screening time point for cognitive decline (Mini-Mental State Examination score

The relationship between openness (a psychological trait of curiosity) and a cognitive change was examined in middle-aged and older adults. Participants were 2214 men and women (baseline age range: 40 to 81 years). They were tested up to seven times over approximately 13 years. Openness at the baseline was assessed by the NEO Five-Factor Inventory. Cognitive abilities were assessed at each examination using the Wechsler adult intelligence scale-revised short form, which includes information, similarities, picture completion, and digit symbol subscales. General linear mixed models comprised fixed effects of openness, age at the baseline, follow-up time, their interactions, and the covariates. The results indicated that the main effects of openness were significant for all scores. Moreover, the interaction term openness &times, age &times, time was significant for the information and similarities test scores, indicating that changes in the information and similarities scores differed depending on the level of openness and baseline age. The estimated trajectory indicated that the differences in slopes between participants with high and low openness were significant after 60 years of age for the information, and after 65 years of age for the similarities scores. It is concluded that openness has a protective effect on the decline in general knowledge and logical abstract thinking in old age.

Inhibition of angiotensin-converting enzyme (ACE) is a strategy used worldwide for managing hypertension. In addition to converting angiotensin I to angiotensin II, ACE also converts neurotoxic β-amyloid protein 42 (Aβ42) to Aβ40. Because of its neurotoxicity, Aβ42 is believed to play a causative role in the development of Alzheimer's disease (AD), whereas Aβ40 has neuroprotective effects against Aβ42 aggregation and also against metal-induced oxidative damage. Whether ACE inhibition enhances Aβ42 aggregation or impairs human cognitive ability are very important issues for preventing AD onset and for optimal hypertension management. In an 8-year longitudinal study, we found here that the mean intelligence quotient of male, but not female, hypertensive patients taking ACE inhibitors declined more rapidly than that of others taking no ACE inhibitors. Moreover, the sera of all AD patients exhibited a decrease in Aβ42-to-Aβ40–converting activity compared with sera from age-matched healthy individuals. Using human amyloid precursor protein transgenic mice, we found that a clinical dose of an ACE inhibitor was sufficient to increase brain amyloid deposition. We also generated human amyloid precursor protein/ACE(+/−) mice and found that a decrease in ACE levels promoted Aβ42 deposition and increased the number of apoptotic neurons. These results suggest that inhibition of ACE activity is a risk factor for impaired human cognition and for triggering AD onset.

Objectives To examine the longitudinal associations between the big five personality and changes in global cognitive function among community-dwelling elderly people involved in the National Institute for Longevity Sciences - Longitudinal Study of Aging. Methods The participants were 594 individuals (age range 60–81 years) and followed for 10 years and tested six times. Personality was assessed by the Japanese version of NEO five factor inventory at baseline. Cognitive function was assessed by the Japanese version of Mini Mental State Examination (MMSE) at all visits. For participants with a baseline MMSE score ≥ 28, logistic generalized estimating equation models estimated the odds ratio (OR) and 95% confidence interval (CI) for MMSE score ≤ 27 at each follow-up visit, according to a 1-SD increase of the baseline personality score. Post hoc analyses were performed for mild cognitive deficits, baseline MMSE score ≥ 24 and ≤ 27, to estimate the OR and CI for MMSE score ≤ 23. Results The adjusted OR for MMSE score ≤ 27 was 0.78 (95% CI, 0.69–0.88), with a 1-SD increase in Openness to Experience score. In post hoc analyses, the adjusted OR for MMSE score ≤ 23 was 0.50 (95% CI, 0.35–0.72) with a 1-SD increase in Conscientiousness score. Relationships between other personality traits and the decline in MMSE score were not significant. Conclusions Higher Openness to Experience was associated with a reduction in risk for cognitive decline in community-dwelling older adults. Higher Conscientiousness might also predict lower risk for severe cognitive decline, especially for individuals with mild cognitive deficits.

Objectives This study aimed to clarify the effects of dietary diversity on a decline in higher-level functional capacity among middle-aged and elderly subjects in Japan. Methods Data were derived from the National Institute for Longevity Sciences - Longitudinal Study of Aging. Subjects comprised 1317 men and women aged 40 to 79 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). Dietary intake was assessed using a 3-d dietary record, and dietary diversity was determined using the Quantitative Index for Dietary Diversity (QUANTIDD). The odds ratios and 95% confidence intervals (CI) for a decline in higher-level functional capacity in the follow-up study according to quartiles of QUANTIDD at baseline were estimated, controlling for age, sex, higher-level functional capacity scores at baseline, body mass index, alcohol consumption, physical activity, depressive score, household income, education, smoking, and disease history. Results A total of 214 (16%), 145 (11%), 70 (5%), and 136 (10%) subjects showed a decline in total score for higher-level functional capacity (≥2), instrumental self-maintenance (≥1), intellectual activity (≥2), and social role (≥2), respectively. Multivariate-adjusted odds ratios (95% confidence intervals) for the score for intellectual activity decline according to the lowest through highest quartiles of QUANTIDD were 1.00 (reference), 0.47 (0.23–0.95), 0.44 (0.22–0.90), and 0.41 (0.20–0.83), respectively (P for trend = 0.06). Conclusions Daily intake of various foods may protect against a decline in intellectual activity among middle-aged and elderly community dwellers in Japan.

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 40–79 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 < 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 ≥ 16) or the last examination participation. Hazard ratios (95% CIs) for CES-D ≥ 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 (0.60–0.93), and highest and middle HRs for DHA were 0.79 (0.63–0.98) and 0.80 (0.65–0.99) (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.

Frailty and sarcopenia present significant risks for adverse outcomes such as disability, falls, and mortality in Japanese older adults. Among community-dwelling Japanese older adults, the prevalence of frailty, which was characterized using three or more limitations(shrinking, exhaustion, low activity, slowness, and weakness), was 5.2% and 12.0% in men and women, respectively. The prevalence of sarcopenia based on a diagnosis of low appendicular muscle mass, low grip strength, and low gait speed was 9.6% in men and 7.7% in women. Further, the prevalence of frailty with comorbidity of sarcopenia was 21.6% and 52.2% in men and women, respectively, and the prevalence of sarcopenia with comorbidity of frailty was 28.6% and 34.4% in men and women, respectively. The estimated number of prevalent cases of frailty, pre-frailty, and sarcopenia in Japanese older adults was approximately 3,090,000, 17,950,000, and 2,710,000, respectively.

Background and objectives Hearing impairment (HI) is a major global health concern. In addition, social networks are important for healthy aging. This study aimed to examine the association between HI and social relationships. Research design and methods This study was conducted by the National Institute for Longevity Sciences as part of its Longitudinal Study of Aging with 1176 Japanese participants aged 60 years or older (mean age 71.0 ± 7.4). The convoy model was used to evaluate participants’ network size. A pure-tone average hearing level (HL) of 0.5, 1, 2, and 4 kHz in the better ear >25 dB HL was defined as HI. Multivariate analysis was performed to assess the relationship between HI and the network size, adjusting for age, gender, years of education, presence of depressive symptoms, and higher-level functional capacity score. Results The mean network sizes across the three circles of the convoy model differed significantly by HI status (18.7 ± 0.4 in the no-HI group vs 17.0 ± 0.5 in the HI group, p = 0.003). In particular, the number of non-kin in the outer circle was significantly less in the HI group (4.1 ± 0.2 vs 3.3 ± 0.3, p = 0.004). Discussion and implications The social network size was significantly smaller in the HI group. The outer circle of people to whom the individual feels less close and the number of non-kin were related to the presence of HI. Therefore, HI may be associated with elderly people’s social relationships.

The association between polypharmacy and the development of frailty is unknown. The present study assessed the longitudinal relationship between polypharmacy and frailty risk in Japanese community-dwelling older adults.Participants included 299 non-frail older Japanese adults aged 65-81 years who participated in both baseline and follow-up examinations of a longitudinal study of aging (mean duration 6.2 years). At baseline examination, all prescribed and non-prescribed medications used during the previous 2 weeks were confirmed and coded by physicians. Frailty was diagnosed according to frailty criteria, and included shrinking, exhaustion, low activity, low grip strength and low gait speed. The relationship between frailty and the number of medications was assessed using multiple logistic regression analysis. The logistic regression model was used to control for potential confounders, including age at baseline, sex, body fat, total physical activity, education, employment, current smoking and number of comorbidities.The percentage of participants who developed frailty during follow up was 5.1% in those taking five or fewer medications, and 22.5% in those taking six or more medications. The fully adjusted odds ratio for frailty among participants taking six or more medications was 5.55 (95% confidence interval 2.17-14.22).Polypharmacy appears to be a significant risk factor for the development of frailty in older Japanese adults. Geriatr Gerontol Int 2018; 18: 1497-1500.

This study describes trends in dietary diversity and food intake over 12 years according to age at first participation in the study. Prospective cohort study. The National Institute for Longevity Sciences-Longitudinal Study of Aging, a community-based study. Participants included 922 men and 879 women who participated in the first study-wave (age, 40-79 years) and also participated in at least one study-wave from the second to seventh study-wave. Study-waves were conducted biennially. Dietary intake was calculated from 3-day dietary records with photographs. Dietary diversity was determined using the Quantitative Index for Dietary Diversity based on food intake. A mixed-effects model was used to estimate linear changes in dietary diversity and food intake over 12 years according to age at first study-wave. Mean (standard deviation (SD)) follow-up time and number of study-wave visits were 9.5 (3.7) years and 5.4 (1.8), respectively. Mean (SD, range) dietary diversity score was 0.86 (0.06, 0.52-0.96) in men and 0.88 (0.04, 0.66-0.96) in women, respectively. Fixed effects for interactions of age and time with dietary diversity score were statistically significant (p

The aims of this study were to determine the prevalence of MRI abnormalities which were suspected as sinusitis in community-dwelling middle-aged and elderly Japanese and to identify risk factors for the MRI abnormality. Brain magnetic resonance imaging (MRI) data from the National Institute for Longevity Sciences, Longitudinal Study of Aging (NILS-LSA) were used for the analysis. Among the 2330 subjects in the NILS-LSA, 1933 participants were categorized as having no MRI abnormality or MRI abnormality using the Lund-Mackay (LM) score. The mean LM score of the participants was 0.88±1.92, and 144 (7.4%) participants had MRI abnormalities which were suspected as sinusitis when it was classified as an LM score greater than or equal to 4. The prevalence of MRI abnormality was significantly higher in participants of older age and the male sex, in participants with obesity, hypertension, bronchial asthma, chronic bronchitis, gout, or hyperuricemia and in ex- or current smokers. A multivariate logistic regression revealed that older age (odds ratio [OR] = 1.17), obesity (OR = 1.54), a smoking habit (OR = 1.71), history of asthma (OR = 3.77), and chronic bronchitis (OR = 2.66) were significant risk factors for MRI abnormality.

The effect ofn-3 long-chain PUFA (n-3 LCPUFA) on depression in healthy subjects is unclear, and most of the previous studies have focused on populations eating Western diets with lower fish intake. The present study investigated the association between blood levels ofn-3 LCPUFA and depressive symptoms in Japanese community dwellers with highern-3 LCPUFA blood levels. A cross-sectional study was conducted from 2006 to 2008, including 1050 men and 1073 women aged 40 years or older from the National Institute for Longevity Sciences – the Longitudinal Study of Aging. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess depressive symptoms. Multiple logistic regression analysis was performed to estimate the OR and 95 % CI for a CES-D score ≥16. Serum concentrations ofn-3 PUFA, but notn-6 PUFA, were inversely associated with depressive symptoms. Compared with the lowest quintile, the adjusted OR for serum EPA at the fourth and fifth quintiles were 0·55 (95 % CI 0·35, 0·85) and 0·64 (95 % CI 0·42, 0·98), respectively, and at the fifth quintile for DHA it was 0·58 (95 % CI 0·37, 0·92), for the presence of depressive symptoms (Pfor trend=0·013 and 0·011, respectively). Serum levels of EPA and DHA were inversely associated with depressive symptoms in Japanese community dwellers with higher blood levels ofn-3 LCPUFA, suggesting thatn-3 LCPUFA intakes corresponding to higher levels in a Japanese population may have implications for a lower prevalence of depression.

Objective This study assessed whether physical function can indicate a risk of decline in higher-level functional capacity. Methods Data were derived from the National Institute for Longevity Sciences—Longitudinal Study of Aging. Subjects comprised 466 men and 495 women aged 40–79 years at baseline (1997–2000), whose total score for the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) at baseline was ≥11 and who participated in the follow-up survey. Baseline physical function examination included grip strength, comfortable gait speed, and sway area with eyes open. A decline in higher-level functional capacity was defined as a ≥2-point decrease in the TMIG-IC score after 14 years. The odds ratios (OR) and 95% confidence intervals (CI) for decline in the TMIG-IC score for 14 years according to a 1-standard deviation (SD) increase in physical function measurements at baseline were estimated. Results Subjects with decreased TMIG-IC scores included 78 (16.7%) men and 80 (16.2%) women. In women, the multivariate-adjusted OR (95% CI) for a TMIG-IC score decrease with a 1-SD increase in comfortable gait speed was 0.68 (0.50–0.92; p = 0.013), and that with a 1-SD increase in sway area with eyes open was 1.49 (1.17–1.90; p = 0.001). Grip strength was not associated with TMIG-IC score decline. None of the physical performance measures affected TMIG-IC score declines in men. Conclusion These results suggest that gait speed decreases and sway area increases might predict a risk of decline in higher-level functional capacity among middle-aged and elderly women.

Background/Objectives: To clarify the association of serum docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) levels with cognitive decline over 10 years. Subjects/Methods: This study was part of the National Institute for Longevity Sciences - Longitudinal Study of Aging, and was conducted with 232 male and 198 female Japanese community-dwelling subjects aged 60–79 years in the second wave (2000–2002). Cognitive function was assessed with the Mini-Mental State Examination (MMSE) in both the second and seventh (2010–2012) waves. Fasting venous blood samples were collected in the morning, and serum DHA and EPA levels were measured. Multiple logistic regression analysis was performed among participants with an MMSE score ⩾24 in the second wave (n=430) to estimate the odds ratio (OR) and 95% confidence interval (CI) for MMSE score ⩽23 or MMSE score decline ⩾4 10 years later. These estimates were based on baseline tertiles of serum DHA or EPA levels, and controlled for age, sex, education, MMSE score at baseline, alcohol consumption, current smoking, body mass index and disease history. Results: Fifteen (3.5%) subjects whose MMSE score was ⩽23 and 36 (8.3%) subjects whose MMSE score declined to ⩾4 showed cognitive decline. Multivariate-adjusted OR (95% CI) for the lowest through highest tertiles of serum DHA to MMSE score ⩽23 or decline⩾4 were 1.00 (reference), 0.11 (0.02–0.58) and 0.17 (0.04–0.74), or 1.00 (reference), 0.22 (0.08–0.61) and 0.31 (0.12–0.75), respectively (P for trend=0.01 or 0.04). Serum EPA was not associated with cognitive decline. Conclusions: The study gives some indication that a moderately high level of serum DHA might prevent cognitive decline among community-dwelling elderly Japanese individuals.

Objectives The relationship between physical frailty and regional gray matter volume in the brain was investigated among community-dwelling older Japanese people. Methods Participants (N = 835; age range 65–89 years) were community-dwelling older adults in Obu City and Higashiura Town in Aichi Prefecture, Japan. Physical frailty was determined by the modified criteria of the Cardiovascular Health Study, which included weight loss, slowness, weakness, exhaustion, and low physical activity. Regional gray matter volumes were evaluated from 3-dimensional T1-weighted magnetic resonance images by statistical parametric mapping. The relationship between physical frailty and regional gray matter volume was analyzed with an analysis of covariance design using statistical parametric mapping adjusting for age, sex, and education level. Results The voxel-based analyses showed that physical frailty per se was not significantly associated with any brain region. However, weakness was associated with reduced gray matter volumes in the hippocampus, amygdala, and fusiform gyrus, and slowness was associated with reduced gray matter volumes in the hippocampus, amygdala, fusiform gyrus, medial prefrontal and orbitofrontal cortex, inferior frontal gyrus, primary somatosensory cortex, insula, superior temporal sulcus, and cerebellum. Other components of physical frailty were not associated with the gray matter volumes in any regions. Conclusions and implications The weakness and slowness components of physical frailty were linked to reduced gray matter volume in brain regions associated with not only physical mobility but also cognitive functions and social processes. This study addressed the underlying mechanisms in the progression of physical, cognitive, and social frailty, from the perspective of brain structures that are associated with frailty.

The associations between meat/fish consumption, docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) intakes, and blood DHA/EPA levels, and mortality in Japan were examined as part of the National Institute for Longevity Sciences-Longitudinal Study of Aging: 520 men and 534 women (60&ndash, 79 years at baseline) were followed from 1997&ndash, 2017. Nutritional intakes were assessed using a 3-day dietary record and fasting venous blood samples were collected. Serum EPA/DHA concentrations, the EPA/arachidonic acid (ARA) ratio, EPA/DHA intakes, and fish/meat intakes were examined in tertiles as indicator variables, and hazard ratios (HR) were calculated to compare the risk of death across tertiles controlling for sex, age, body mass index, smoking status, alcohol drinking, physical activity, education, employment, and history of diseases. During follow-up (mean 11.7 years), 422 subjects (40.4%) died. The multivariate-adjusted HR for all-cause mortality in subjects in the highest tertile of serum DHA and EPA/ARA ratio was 0.73 (95% confidence intervals (CI): 0.53&ndash, 0.99) and 0.71 (95% CI: 0.53&ndash, 0.96) compared with subjects in the lowest tertile, respectively (trend p &lt, 0.05). There were no significant associations between mortality and serum EPA/ARA and DHA/EPA intakes. An increased serum DHA level or EPA/ARA ratio might be recommended for longevity to Japanese community dwellers.

The association of knee extensor muscle strength with bone mineral density (BMD) has been reported in cross-sectional epidemiological studies, but it remains unclear whether or not this is the case with longitudinal change. Thus, we investigated whether or not the knee extension strength can predict the incidence of osteopenia or osteoporosis after 6 years, then compared the difference between sexes. Subjects were 1255 community-dwelling Japanese men and menopaused women, aged 40–81 years. BMD of lumbar spine and femoral neck was assessed by dual-energy X-ray absorptiometry twice at 6-year intervals. Subjects were divided into three groups, normal, osteopenia, and osteoporosis, depending on their young adult mean BMD % value. In the cross-sectional analysis the correlations between the knee extension strength and BMD of the two regions were examined, using Pearson’s correlation coefficient. Longitudinal analyses were then conducted to determine the odds ratio, controlled for age and BMI, given that those who were normal in the initial stage developed osteopenia or osteoporosis after 6 years, for every 1 SD decrease in knee extension strength, as well as those who first had normal or osteopenia and then developed osteoporosis. Cross-sectional analysis showed a statistically significant relation between knee extensor muscle strength and BMD at both the lumbar spine (p = 0.02) and the femoral neck (p

Folate metabolism is essential for cellular functioning. Despite extensive research on the roles of folate-metabolism-related gene polymorphisms in the pathophysiology of many diseases, such as cardiovascular disease, cancers, and sudden sensorineural hearing loss, little is known about their association with Ménière's disease (MD). The aim of this study was to investigate the effect of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (C677T and A1298C) on the risk of MD in a Japanese population. We examined the C677T and A1298C (rs1801133 and rs1801131) polymorphisms in the MTHFR gene and compared them between 1946 adults (986 men and 960 women) participating in the National Institute for Longevity Sciences Longitudinal Study of Aging and 86 cases of MD. A multiple logistic regression was performed to obtain odds ratios (ORs) for the risk of MD regarding the MTHFR polymorphisms before (model 1) and after (model 2) adjustment for age and sex factors. The OR of MTHFR C677T for the risk of MD was 0.669 (95% confidence interval [CI], 0.479-0.934) in model 1 and 0.680 (95% CI, 0.484-0.954) in model 2. In contrast, the OR of MTHFR A1298C for the risk of MD was 1.503 (95% CI, 1.064-2.123) in model 1 and 1.505 (95% CI, 1.045-2.167) in model 2. Our results imply that the MTHFR C677T and A1298C polymorphisms are associated with the risk of MD.

Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are the predominant long-chain polyunsaturated fatty acids (PUFA) among membrane phospholipids in the mammalian brain and neural tissues. This cross-sectional study examined age effects on serum eicosapentaenoic acid (EPA), DHA, and ARA compositions assessed with reference to dietary intakes among 1,014 Japanese men and 1,028 Japanese women aged 40-79 years. Venous blood was collected early in the morning after at least 12-h fasting. Serum fatty acid (FA) compositions were expressed as molar percentages of the total FA (mol% of total). Diet was assessed using a 3-day dietary record that included photographs. Participants were categorized into groups by sex and age (40-49, 50-59, 60-69, and 70-79 years). Intakes of fish, EPA, and DHA tended to increase with age. Significant positive correlations between serum FA composition and the corresponding weight percentage of total FA intake were observed for EPA and DHA in all sex and age groups, and for ARA among females in their 40s. Serum EPA and DHA compositions were higher, while ARA decreased with age, and these associations remained consistent even after adjusting for corresponding FA intake. These results suggest potential effects of age on differences in blood EPA, DHA, and ARA compositions, independent of corresponding FA intake among community-dwelling Japanese men and women.

AIM: The purpose of this study was to construct a scale that measures multidimensional attitudes regarding death in the middle-aged and elderly, using scale items for adolescents, and to examine its reliability and validity. METHODS: Twenty-nine items which were selected from the scale of Attitudes toward Death (Tange, 1999) were administered to subjects, consisting of 2,223 community-living Japanese men and women aged 40-79 years. Both exploratory factor analysis and confirmatory factor analysis were performed to examine the factor structures. The reliability and validity of the scale were examined. RESULTS: Exploratory factor analysis was performed to examine the factor structures of death attitudes, using the data from half of the subjects, indicated 5 factors. Confirmatory factor analysis, using the data from the remaining half, supported the goodness of fit of that model. Using this structure, the attitude toward death scale for the middle-aged and elderly (ATDS-A; five subscales) was constructed; "fear of death", "belief in existence of afterlife", "intention to live out own life", "meaning of death for life", "approval of death with dignity". For these subscales, the alpha coefficients ranged from 0.59-0.87. The validity of the subscales was suggested through the relation with the ego integration score. CONCLUSIONS: This study suggested that the ATDS-A was reliable and valid, and was useful for the measurement of death attitudes in the middle-aged and elderly. Language: en

A normal value is a laboratory parameter to discriminate between "normal" and "abnormal" in clinical decision-making. Because individual differences in the elderly are large, it can be difficult to determine a normal value as a group, thus reference values are basically used to assess laboratory parameters. However, the reference value only shows the range of average values in the healthy population, and does not determine or predict present and future health status. In geriatric practice, reference values of laboratory parameters in life-style related disease to predict independent life is indispensable. Although there are many risk factors of cognitive impairment related to independent life, the contribution rate of each factor is small and it is often difficult to determine a cut-off point by conventional methods. A new methodology is required to determine the optimal range of clinical parameter of life-style-related disease using longitudinal data.

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.

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.

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.

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.

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.