Relation between number of teeth, malnutrition, and 3-year mortality in elderly individuals ≥85 years.

OBJECTIVE: The number of teeth has been shown to affect mortality. However, it is unclear why the number of teeth is associated with mortality. We focused on the number of teeth and malnutrition and examined whether these differences affect 3-year all-cause mortality among very elderly individuals. METHODS: This analysis was conducted using data from the Tokyo Oldest Old Survey on Total Health study. Altogether 513 participants ≥85 years were categorized based on remaining teeth (0, 1-7, 8-18, ≥19). All-cause mortality was determined by calculating the cumulative 3-year survival rate according to the remaining number of teeth and the presence/absence of malnutrition. Further, hazard ratios (HRs) were analyzed using Cox regression analyses. RESULTS: No difference was observed according to the number of teeth (p = 0.638), but the presence/absence of malnutrition was significantly associated with mortality (p < 0.001). Malnutrition was independently associated with higher HRs, even after adjusting for confounding factors associated with mortality. (HR: 2.315, 95% CI: 1.431-3.746). Additionally, adjusting for the number of teeth, HR remained significant (HR: 2.365, 95% CI: 1.449-3.853). CONCLUSION: In the very elderly, malnutrition-but not the number of teeth-was independently associated with 3-year all-cause mortality after adjusting for various health issues.

[Identification of dietary patterns and their relationship with physical performance in adults of 85 years of age and older -A cross sectional study from The Tokyo Oldest Old survey on Total Health study].

AIM: While the proportion of people of ≥85 years of age is expected to increase, there is limited research on the dietary patterns and physical performance of this population in Japan. The purpose of this study was to identify the dietary patterns of people of ≥85 years of age who live in Tokyo and to examine the relationship with their physical performance. METHODS: Using data from the baseline survey (conducted in 2008-2009) of The Tokyo Oldest Old survey on Total Health study, the estimated 58 food intake items were aggregated into 33 items after energy adjustment, and a principal component analysis was performed. For physical performance, the results of grip strength, chair standing test, and 3 m timed up and go test conducted at normal walking speed were used. A multiple regression analysis was used to adjust for confounders and to examine the relationship between each dietary pattern and physical performance. RESULTS: The subjects of the analysis were 87.3 (86.2-88.8) years of age (median [25-75th percentile] ). From the principal component analysis, three dietary patterns were identified: "various vegetable foods", "fish and mushrooms", and "cooked rice and miso soup". A higher propensity for the "fish and mushrooms" dietary pattern was significantly associated with grip strength (partial regression coefficient, B (95% confidence interval): 0.48 (0.13-0.83) ). CONCLUSIONS: In a population of people of ≥85 years of age in Tokyo, a positive association was observed between hand grip strength and a dietary pattern characterized by fish and mushroom intake.

Associations of poor oral health with frailty and physical functioning in the oldest old: results from two studies in England and Japan.

BACKGROUND: Very few studies have examined the relationship of oral health with physical functioning and frailty in the oldest old (> 85 years). We examined the association of poor oral health with markers of disability, physical function and frailty in studies of oldest old in England and Japan. METHODS: The Newcastle 85+ Study in England (n = 853) and the Tokyo Oldest Old Survey on Total Health (TOOTH; n = 542) comprise random samples of people aged > 85 years. Oral health markers included tooth loss, dryness of mouth, difficulty swallowing and difficulty eating due to dental problems. Physical functioning was based on grip strength and gait speed; disability was assessed as mobility limitations. Frailty was ascertained using the Fried frailty phenotype. Cross-sectional analyses were undertaken using logistic regression. RESULTS: In the Newcastle 85+ Study, dry mouth symptoms, difficulty swallowing, difficulty eating, and tooth loss were associated with increased risks of mobility limitations after adjustment for sex, socioeconomic position, behavioural factors and co-morbidities [odds ratios (95%CIs) were 1.76 (1.26-2.46); 2.52 (1.56-4.08); 2.89 (1.52-5.50); 2.59 (1.44-4.65) respectively]. Similar results were observed for slow gait speed. Difficulty eating was associated with weak grip strength and frailty on full adjustment. In the TOOTH Study, difficulty eating was associated with increased risks of frailty, mobility limitations and slow gait speed; and complete tooth loss was associated with increased risk of frailty. CONCLUSION: Different markers of poor oral health are independently associated with worse physical functioning and frailty in the oldest old age groups. Research to understand the underlying pathways is needed.

Potential association of metabolic and musculoskeletal disorders with lumbar intervertebral disc degeneration: Cross-sectional study using medical checkup data.

BACKGROUND: The pathogenesis of intervertebral disc (IVD) degeneration is complex and involves the interaction of multiple factors. However, few systemic studies have explored the associations of metabolic disorders and age-related musculoskeletal disorders with the development of IVD degeneration. METHODS: We analyzed clinical data obtained from healthy individuals who had undergone a musculoskeletal checkup. In total, 276 subjects comprising 142 males and 134 females were enrolled. The subjects were divided into two groups based on the degree of IVD degeneration according to Pfirrmann grading: those with grades 1-3, the group with non-degenerative discs; and grades 4 and 5, the group with degenerative discs. The subjects underwent examinations including abdominal circumference, blood pressure, bilateral hand grip strength, abdominal computed tomography, magnetic resonance imaging of the lumbar spine, and dual X-ray absorptiometry. To examine the independent association with IVD degeneration at L3/4, L4/5, and L5/S levels, we constructed a Poisson regression model and estimated relative risks (RRs) and 95% confidence intervals (CIs) of IVD degeneration. RESULTS: Multivariable analysis showed that advanced age was markedly associated with IVD degeneration at all levels and that men had an inverse association with the IVD degeneration, particularly at the L4/5 level (RR = 0.7, 95% CI = 0.6-0.9). In addition, metabolic syndrome was significantly associated with IVD degeneration at the L5/S level (RR = 1.4, 95% CI = 1.1-1.8). Meanwhile, sarcopenia showed no significant association with IVD degeneration at any level. Osteoporosis was inversely associated with IVD degeneration, particularly at the L4/5 level (RR = 0.7, 95% CI = 0.6-0.9). CONCLUSIONS: Our data suggest that advanced age, female sex, and metabolic syndrome are associated with IVD degeneration. In addition, osteoporosis showed an inverse association with IVD degeneration. Our data should promote understanding of the etiology of lumbar IVD degeneration.

Relative validity of brief-type self-administered diet history questionnaire among very old Japanese aged 80 years or older.

OBJECTIVE: Dietary questionnaires for assessing dietary intakes among populations of individuals aged 80 years or older (the very old) are very limited. We examined the relative validity of forty-three nutrients and twenty-seven food groups estimated by a brief-type self-administered diet history questionnaire (BDHQ) targeting very old Japanese, using semi-weighed dietary records (DR) as a reference. DESIGN: Between June and August 2012 and between June 2015 and February 2016, a three-day non-consecutive DR (at two-week intervals) and a BDHQ were completed. SETTING: Tokyo, the capital prefecture of Japan. SUBJECTS: Eighty very old Japanese (thirty-six men and forty-four women) aged 82-94 years. RESULTS: The median intakes of 40-70 % of the crude and energy-adjusted nutrients estimated by the BDHQ were significantly different from those estimated by the DR. The median Spearman's correlation coefficient of nutrient intakes between the BDHQ and the DR was 0·39-0·46. About half (48-56 %) of the food groups were significantly different in terms of the median intakes estimated by the BDHQ and the DR in crude and energy-adjusted values. The median Spearman's correlation coefficient between the BDHQ and the DR was 0·45-0·48. CONCLUSIONS: Acceptable Spearman's correlations (≥0·3) were obtained for many dietary intakes among the very old Japanese population. The BDHQ is a good candidate for epidemiological studies among very old Japanese, although, for some nutrients and food groups, the difficulty of estimating accurate median intakes is one of the limitations for the tool. Further efforts to enhance the validity of the BDHQ for very old populations are needed.

Association of Kidney Dysfunction With Asymptomatic Cerebrovascular Abnormalities in a Japanese Population With Health Checkups.

BACKGROUND: Cerebrovascular disease is a major cause of mortality and morbidity. Chronic kidney disease (CKD) is prevalent in stroke patients. This study evaluated the correlation between kidney dysfunction and asymptomatic findings on carotid ultrasonography (US) and brain magnetic resonance imaging (MRI) in a Japanese population with health checkups.Methods and Results:In total, 1,716 subjects aged 40-80 years, who received health checkups from January 1 to December 31, 2015, were included. Common carotid artery intima-media thickness (CCA-IMT) and carotid plaques by US, and the presence of old non-lacunar infarctions, lacunar infarctions, white matter lesions (WMLs), cerebral microbleeds (CMBs), and atrophy by brain MRI were evaluated. After adjusting for cardiovascular risk factors, multiple regression analyses revealed that an eGFR ranging from 15 to 44 mL/min/1.73 m2was independently associated with CCA plaques and hypoechoic or heterogeneous plaques. Proteinuria was associated with CCA or internal carotid artery plaques, the number of carotid plaques, and the presence of old non-lacunar infarctions and CMBs. CONCLUSIONS: Decreased eGFR and proteinuria were independent risk factors for asymptomatic abnormalities on carotid US and brain MRI, which are surrogate markers for cerebrovascular diseases. Evaluation of these abnormalities may be useful for prevention of symptomatic cerebrovascular events in CKD patients.

Relationships of Muscle Echo Intensity with Walking Ability and Physical Activity in the Very Old Population.

This study investigated the relationships between muscle echo intensity (EI), physical activity (PA), and functional mobility in 108 Japanese (88-92 years). We measured EI and muscle thickness (MT) at the midpoint of the anterior superior iliac spine and patella using B-mode ultrasound. Light and moderate-to-vigorous PA (LPA and MVPA) were assessed with a triaxial accelerometer. The timed up and go (TUG) test was used to measure for functional mobility. EI, but not MT, was significantly associated with both TUG scores (ß = 0.17, p = .047) and MVPA (ß = -0.31, p = .01) when adjusted by potential confounders. However, association between EI and TUG disappeared after adjusted for MVPA. Meanwhile, MVPA was significantly associated with TUG scores independent of EI (ß = -0.35, p < .001). Although EI of anterior thigh muscles might be a weaker predictor of functional morbidity than MVPA, it is a noninvasive and practical approach for assessing muscle quality in the very old.

Perceived swallowing problems and mortality risk in very elderly people ≥85 years old: Results of the Tokyo Oldest Old Survey on Total Health study.

OBJECTIVE: The aim of this study was to clarify whether perceived swallowing problems affect the life expectancy of very elderly individuals. BACKGROUND: In an ageing society, oral function affects health status. In particular, a decline in swallowing function may increase the risk of various diseases, morbidity and malnutrition. MATERIALS AND METHODS: We evaluated 526 elderly individuals aged ≥85 years. All participants completed a questionnaire and underwent oral, physical and mental health examinations. The comprehensive oral health assessment comprised a face-to-face interview that included a questionnaire on swallowing function. We estimated hazard ratios and 95% confidence intervals using the Cox proportional hazards model, adjusting for potential confounders between perceived swallowing problems and all-cause mortality over a 3-year period. RESULTS: Over a 3-year follow-up period, 88 of 526 participants died and 68 participants complained of perceived swallowing problems. Perceived swallowing problems had statistically significant associations with physical status and function and nutrition. In the univariate analysis, perceived swallowing problems had statistically significant associations with an approximately 1.9-fold higher risk of all-cause mortality during the 3-year period (HR: 1.89, 95% CI: 1.14-3.14). In the multivariate analysis, the statistically significant association between perceived swallowing problems and all-cause mortality remained after adjusting for various confounding factors (HR: 1.73, 95% CI: 1.03-2.92). CONCLUSION: Perceived swallowing disorders should be verified by a clinical examination, as they are associated with other health outcomes and increased all-cause mortality.

The drug burden of anticholinergics and sedatives and influence on outcomes in the community-living oldest old: The Tokyo Oldest Old survey on Total Health (TOOTH) survey.

AIM: The objective of this study was to assess the burdens of anticholinergic and sedative drugs in community-living individuals of 85 years of age or older. METHODS: The Tokyo Oldest Old survey on Total Health (TOOTH) is a cohort study designed to assess the physical, mental, and oral health of the community-living oldest old. We investigated the relationships between the anticholinergic/sedative burden and physical/cognitive outcomes. The drug burden was assessed by the Drug Burden Index (DBI). Relationships between the DBI score and the physical/cognitive outcomes were evaluated by multivariate regression. The age-related changes (baseline to 3-year follow-up) of these outcomes were also investigated. RESULTS: At baseline, the data of 306 subjects were subjected to a cross-sectional analysis. The Instrumental Activities of Daily Living and Mini Mental State Examination scores were found to be significantly associated with the DBI score. After 3 years, the Activities of Daily Living score was significantly associated with the DBI score in 176 subjects. Changes in these outcome measures were small during the 3-year follow-up period and were not associated with the DBI scores at baseline. DISCUSSION: DBI in the community-living oldest old were evaluated. Our findings suggest that anticholinergic and sedative drugs may influence the physical and cognitive function in the oldest old. Additional studies should be performed to investigate the relationships between the change of the physical/cognitive functions and the DBI score over a long-term observation period.

Association between maximum occlusal force and 3-year all-cause mortality in community-dwelling elderly people.

BACKGROUND: Among the very elderly, poor oral health reduces life expectancy. In this study, differences in the magnitude of the maximum occlusal force (MOF) in the very elderly were examined in terms of effects on all-cause mortality in a 3-year follow-up. METHODS: We evaluated 489 community-living elderly individuals aged 85 years or older. MOF was measured using an occlusal force measuring device, and participants were classified into three groups according to gender- and dental status-sensitive tertiles. Demographic variables, cognitive, physical function, psychological status, oral health, comorbidity, and blood chemistry factors were assessed. One-way analyses of variance, χ (2) tests, and the Kruskal-Wallis test were used for statistical analyses. The relationship between MOF tertiles and 3-year all-cause mortality was examined using a multivariate Cox model analysis after adjusting for confounding factors. RESULTS: MOF tertiles were significantly associated with cognitive impairment, number of teeth, limitations on chewable foods, handgrip strength, timed up-and-go test, and diabetes mellitus. During the follow-up period, 74 subjects died. Subjects with the highest MOF had a significantly lower mortality rate than other groups (log rank P  =  0.031). In the univariate Cox model, MOF tertiles were independently associated with a lower risk of death (HR = 0.69, 95 % CI = 0.51-0.91). Even after adjusting for various confounders in the multivariate Cox model (Model 1), MOF was independently associated with a lower risk of death (HR = 0.67, 95 % CI = 0.50-0.91). In model 2, we added handgrip strength as a confounder and found that the HR for MOF was attenuated (HR = 0.73, 95 % CI = 0.54-0.99), but still statistically significant. CONCLUSIONS: In a cohort of the very elderly, MOF was independently associated with all-cause mortality after adjusting for various health issues. Moreover, this independent association remained after a further adjustment for handgrip strength; however, the HR was attenuated. This suggests that MOF and handgrip strength may share a common mechanism of a general decrease in muscle strength, possibly sarcopenia, which is a significant cause of mortality in the very old.

Status and physiological significance of circulating adiponectin in the very old and centenarians: an observational study.

Background: High levels of circulating adiponectin are associated with increased insulin sensitivity, low prevalence of diabetes, and low body mass index (BMI); however, high levels of circulating adiponectin are also associated with increased mortality in the 60-70 age group. In this study, we aimed to clarify factors associated with circulating high-molecular-weight (cHMW) adiponectin levels and their association with mortality in the very old (85-89 years of age) and centenarians. Methods: The study included 812 (women: 84.4%) for centenarians and 1498 (women: 51.7%) for the very old. The genomic DNA sequence data were obtained by whole-genome sequencing or DNA microarray-imputation methods. Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate regression analyses were used to evaluate cHMW adiponectin characteristics and associated factors. All-cause mortality was analyzed in three quantile groups of cHMW adiponectin levels using Cox regression. Results: The cHMW adiponectin levels were increased significantly beyond 100 years of age, were negatively associated with diabetes prevalence, and were associated with SNVs in CDH13 (p=2.21 × 10-22) and ADIPOQ (p=5.72 × 10-7). Multivariate regression analysis revealed that genetic variants, BMI, and high-density lipoprotein cholesterol (HDLC) were the main factors associated with cHMW adiponectin levels in the very old, whereas the BMI showed no association in centenarians. The hazard ratios for all-cause mortality in the intermediate and high cHMW adiponectin groups in very old men were significantly higher rather than those for all-cause mortality in the low-level cHMW adiponectin group, even after adjustment with BMI. In contrast, the hazard ratios for all-cause mortality were significantly higher for high cHMW adiponectin groups in very old women, but were not significant after adjustment with BMI. Conclusions: cHMW adiponectin levels increased with age until centenarians, and the contribution of known major factors associated with cHMW adiponectin levels, including BMI and HDLC, varies with age, suggesting that its physiological significance also varies with age in the oldest old. Funding: This study was supported by grants from the Ministry of Health, Welfare, and Labour for the Scientific Research Projects for Longevity; a Grant-in-Aid for Scientific Research (No 21590775, 24590898, 15KT0009, 18H03055, 20K20409, 20K07792, 23H03337) from the Japan Society for the Promotion of Science; Keio University Global Research Institute (KGRI), Kanagawa Institute of Industrial Science and Technology (KISTEC), Japan Science and Technology Agency (JST) Research Complex Program "Tonomachi Research Complex" Wellbeing Research Campus: Creating new values through technological and social innovation (JP15667051), the Program for an Integrated Database of Clinical and Genomic Information from the Japan Agency for Medical Research and Development (No. 16kk0205009h001, 17jm0210051h0001, 19dk0207045h0001); the medical-welfare-food-agriculture collaborative consortium project from the Japan Ministry of Agriculture, Forestry, and Fisheries; and the Biobank Japan Program from the Ministry of Education, Culture, Sports, and Technology.

Relationship between Dietary Patterns and Subjectively Measured Physical Activity in Japanese Individuals 85 Years and Older: A Cross-Sectional Study.

High-quality diets and regular physical activity (PA) are considered healthy behaviors (HBs). HBs are associated with many health outcomes and are expected to improve quality of life. Although implementing HBs is important, the relationship between dietary patterns (DPs) and PA has not been well investigated, especially among those aged ≥ 85. This study used data from the Tokyo Oldest Old survey on Total Health study to examine the relationship between DPs and PA in a cross-sectional study. The dietary survey used the brief self-administered diet history questionnaire to estimate the intake of 58 foods. After energy adjustment, principal component analysis was performed to identify major DPs. A validated questionnaire was used to evaluate PA, and linear regression analysis was used to investigate the association between DPs and PA, considering confounders. A total of 519 participants were included. Three major DPs ('Various plant foods', 'Fish and mushrooms', 'Cooked rice and miso soup') were identified. 'Various plant foods' was similar to DPs previously named 'Healthy' or 'Prudent', and its trend was positively associated with higher PA. This study observed the implementation of HBs even among those aged ≥ 85, suggesting that a trend toward a healthier diet is associated with higher PA.

Physical activity and all-cause mortality and mediators of the association in the very old.

BACKGROUND AND OBJECTIVE: Physical activity (PA) confers protection to individuals from the risk of death. However, in the very old, the dose-response relationship between PA and all-cause mortality and the possible biological mediators of this association are less known. We investigated whether PA predicts 6-year all-cause mortality and what biomarkers mediate the association. DESIGN: Prospective cohort data from the Tokyo Oldest Old Survey on Total Health study. SETTING: Community-dwelling population. PARTICIPANTS: A total of 441 women and men aged over 85 years. MEASUREMENTS: Questionnaire-based PA was assessed at baseline and 3-year and 6-year follow-up visits. Survival status was confirmed up to the 6-year follow-up visit (153 deaths, 34.7%). Data of plasma albumin, cholinesterase, NT-proBNP, interleukin-6, cystatin C, and HbA1c levels were collected. For mediation analysis for survival analysis, we used the baseline PA and biomarkers with Weibull distribution accelerated failure time model and linear regression model adjusted for age, sex, body mass index, smoking, education level, and Mini-Mental State Examination. RESULTS: A curvilinear relationship was observed in the association between baseline PA and all-cause mortality. Compared to the inactive (0 METs*h/week), light amount of PA was associated with a lower risk of mortality. Compared to the highest tertile of PA (11.2 METs*h/week), higher PA did not reduce the risk of death. Circulation levels of albumin and cholinesterase mediated the association between baseline PA and all-cause mortality (proportion mediated, 54%, both; p < 0.05). CONCLUSIONS: Compared to completely inactive, light PA reduces the risk of all-cause mortality in the very old population. Mediation analysis suggests that protein synthesis in the liver may mediate the association between PA and all-cause mortality. Further studies are needed to understand the underlying association between PA, nutrition, and death.

A significant association of non-obese non-alcoholic fatty liver disease with osteosarcopenic obesity in females 50 years and older.

BACKGROUND & AIMS: Osteosarcopenic obesity (OSO) encompassing obesity, sarcopenia and osteopenia, is due to redistribution or infiltration of fat into muscle and bone. This cross-sectional study evaluated the association between OSO and non-alcoholic fatty liver disease (NAFLD). METHODS: Obesity, sarcopenia and osteopenia was defined using the percentage of body fat mass, reduced muscle mass, and the percentage of young adult mean < 80%, measured by dual-energy x-ray absorptiometry, respectively. Non-obese and obese NAFLD was diagnosed by ultrasound and body mass index cut-off point (25 kg/m2). A total of 619 subjects ≥ 50 years who completed health checkups were divided into obesity group including OSO and sarcopenic obesity (SO) alone phenotype, and non-obesity group that did not belong to any phenotype, including standard (St). RESULTS: Overall osteopenia and OSO were detected in only 10% and 1% in males, compared with 45% and 9% in females, respectively. Multivariate analysis for females demonstrated a significant association of OSO with non-obese NAFLD (odds ratio = 3.737, 95% confidence interval = 1.365-10.233, P = 0.010), while the association between SO alone and non-obese NAFLD was equivocal. The OSO phenotype had a significantly higher proportion of slower walking speed and weaker grip strength, compared to the St phenotype. The proportion of OSO increased with age in contrast to constant prevalence of non-obese NAFLD. CONCLUSION: Non-obese NAFLD had a significant association with OSO in females, independent of plausible confounders. These results suggest that non-obese NAFLD might be an independent risk factor for OSO.

Association among extracellular superoxide dismutase genotype, plasma concentration, and comorbidity in the very old and centenarians.

Superoxide dismutase 3 (SOD3), an antioxidant enzyme, is known as extracellular SOD (EC-SOD) because it is the predominant form in extracellular fluids. The diversity of plasma EC-SOD concentration is associated with the SOD3 p.R231G missense variant genotype. To clarify the association among SOD3 genotype, plasma EC-SOD concentration, and comorbidity in Oldest Old, we analyzed genome-wide associations with plasma EC-SOD concentration and associations between EC-SOD concentration and medical history classified by the SOD3 genotype in the Very Old (85-99 years old, n = 505) and Centenarians (over 100 years old, n = 595). The results revealed that SOD3 p.R231G was the most significant variant associated with plasma EC-SOD concentration. Although no significant difference was observed in medical histories between the SOD3 p.R231G variant non-carriers and carriers, higher EC-SOD concentration in plasma of SOD3 p.R231G variant non-carriers was associated with a high odds ratio for chronic kidney disease (OR = 2.70, 95% CI = 1.98-3.72) and low odds ratio for diabetes mellitus (DM) (OR = 0.61, 95% CI = 0.39-0.95). Comparison with 11 plasma biomarkers for age-related disease showed that plasma EC-SOD concentration correlated with adiponectin and estimated glomerular filtration rate with creatinine correction; therefore, we deduced that EC-SOD co-operates with adiponectin and possesses beneficial functions for DM in the Oldest Old.

Metabolic Syndrome is a Predisposing Factor for Diffuse Idiopathic Skeletal Hyperostosis.

OBJECTIVE: Diffuse idiopathic skeletal hyperostosis (DISH) causes spinal ankylosis, which can result in patients suffering specific spinal fractures that lead to a reduction in the activities of daily life in older patients. Currently, DISH is associated with diabetes mellitus and cardiovascular disease; however, the association between DISH and metabolic syndrome has not been established. The purpose of this study was to investigate a potential association between DISH and metabolic syndrome. METHODS: We retrospectively reviewed clinical data from consecutive subjects undergoing the musculoskeletal health medical checkups, and enrolled 327 subjects (174 men and 153 women; mean, 63.4 ± 13.7-years). Subjects who had spinal ankylosis at least 4 contiguous vertebral bodies were classified as the DISH group (n = 39) while the others were part of the non-DISH group (n = 288). The definition of the metabolic syndrome comes from diagnostic criteria used by the Japanese Society for Internal Medicine. Age, sex, body max index (BMI), hematological evaluation, blood pressure, presence of metabolic syndrome, the visceral fat area on abdominal computed tomography, and spinal epidural lipomatosis (SEL) on magnetic resonance imaging were evaluated. RESULTS: Compared to the non-DISH group, in the DISH group, mean age (DISH group, 74.3 years; non-DISH group, 1.9 years; p < 0.001), male prevalence were higher (DISH group, 82.1%; non-DISH group, 49.3%; p < 0.001), and BMI was greater (DISH group, 24.8; non-DISH group, 23.0; p = 0.006). the metabolic syndrome was more frequently observed in DISH group (28.9%) than in the non-DISH group (16.0%) (p = 0.045). The visceral fat area was significantly larger in the DISH group than in the non-DISH group (DISH group, 130.7 ± 58.2 cm2; Non-DISH group, 89.0 ± 48.1 cm2; p < 0.001). The prevalence of SEL was similar between the 2 groups (10.3% in the DISH group vs. 8.7% in the nonDISH group; p = 0.464). Poisson regression analysis revealed that the metabolic syndrome was significantly associated with DISH with odds ratio of 2.0 (95% confidence interval, 1.0-3.7; p = 0.004). CONCLUSION: Metabolic syndrome was significantly associated with DISH. Our data showed metabolic syndrome is potentially related to DISH.

The Tokyo Oldest Old survey on Total Health (TOOTH): a longitudinal cohort study of multidimensional components of health and well-being.

BACKGROUND: With the rapid worldwide increase in the oldest old population, considerable concern has arisen about the social and economic burden of diseases and disability in this age group. Understanding of multidimensional structure of health and its life-course trajectory is an essential prerequisite for effective health care delivery. Therefore, we organized an interdisciplinary research team consisting of geriatricians, dentists, psychologists, sociologists, and epidemiologists to conduct a longitudinal observational study. METHODS/DESIGN: For the Tokyo Oldest Old Survey on Total Health (TOOTH) study, a random sample of inhabitants of the city of Tokyo, aged 85 years or older, was drawn from the basic city registry. The baseline comprehensive assessment consists of an in-home interview, a self-administered questionnaire, and a medical/dental examination. To perform a wide variety of biomedical measurements, including carotid ultrasonography and a detailed dental examination, participants were invited to our study center at Keio University Hospital. For those who were not able to visit the study center, we provided the option of a home-based examination, in which participants were simultaneously visited by a geriatrician and a dentist. Of 2875 eligible individuals, a total of 1152 people were recruited, of which 542 completed both the in-home interview and the medical/dental examination, with 442 completed the in-home interview only, and another 168 completed self or proxy-administered data collection only. Carotid ultrasonography was completed in 458 subjects, which was 99.6% of the clinic visitors (n = 460). Masticatory assessment using a colour-changeable chewing gum was completed in 421 subjects, a 91.5% of the clinic visitors. DISCUSSION: Our results demonstrated the feasibility of a new comprehensive study that incorporated non-invasive measurements of subclinical diseases and a detailed dental examination aiming at community-dwelling individuals aged 85 years or older. The bimodal recruitment strategy is critically important to capture a broad range of health profiles among the oldest old. Results form the TOOTH study will help develop new models of health promotion, which are expected to contribute to an improvement in lifelong health and well-being.

Sex-Specific Effects of Apolipoprotein ε4 Allele on Mortality in Very Old and Centenarian Japanese Men.

The apolipoprotein E4 (APOE ε4) allele has attracted attention as an age-related genetic factor, both in neurology and gerontology. To understand the effects of the APOE ε4 allele on mortality in elderly individuals, we combined Japanese prospective cohort studies comprising 535 very old individuals (85-99 years of age) and 930 centenarians (over 100 years of age) and analyzed the association between mortality rates and candidate factors, including the APOE ε4 allele. APOE genotyping revealed an inverse correlation between the APOE ε4 allele carrier rate and age. Additionally, APOE ε4 allele carrier rate in centenarian men was significantly lower than that in centenarian women. The association analysis between APOE ε4 allele carriers and all-cause mortality indicated that APOE ε4 carriers showed significantly higher mortality rates than the APOE ε4 noncarriers among men in the very old group. Further analysis using Cox proportional hazard models indicated that cause-specific mortalities, including pneumonia and severe dementia, were associated with APOE ε4 carriers. These findings indicate that the APOE ε4 allele shows phenotypic male-specific adverse effects in the very old, which would explain the high mortality rate observed in this group, resulting in a low APOE ε4 allele carrier rate in centenarian men.

A significant association of non-obese non-alcoholic fatty liver disease with sarcopenic obesity.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is significantly related to sarcopenia as well as obesity and its associated comorbidities. This cross-sectional study aims to examine the association between four body composition phenotypes (standard, obesity alone, sarcopenia alone, sarcopenic obesity) and non-obese NAFLD, or obese NAFLD. METHODS: Reduced muscle mass and high percentage of body fat mass was measured by dual-energy x-ray absorptiometry, and body composition phenotypes were determined, according to Asian criteria for sarcopenia. Based on body mass index (BMI) cut-off point (25 kg/m2) and hepatic steatosis on ultrasound, 748 subjects who underwent a health checkup were enrolled and divided into three groups: non-obese NAFLD, obese NAFLD, and no steatosis. RESULTS: Of 563 subjects (64.1 ± 13.0 years) without secondary causes for steatosis, the overall prevalence of non-obese NAFLD and obese NAFLD were 17% and 16%, respectively. The former prevalence remained relatively constant at around 20% from the 50s to 80's, while the proportion of sarcopenic obesity in all subjects increased gradually with age, reaching 18% in the 80's. Multivariate analysis demonstrated a significant association between sarcopenic obesity and non-obese NAFLD after adjusting for confounders (odds ratio = 2.367, 95% confidence interval = 1.317-4.254, P = 0.004). On the other hand, no significant association was found between obesity alone and obese NAFLD, when BMI and visceral adipose tissue were added as confounders, although 91% of obese NAFLD was included in obesity alone phenotype. CONCLUSION: Non-obese NAFLD had a significant association with sarcopenic obesity, independent of metabolic confounders. Early treatment intervention for non-obese NAFLD could suppress the deterioration of sarcopenic obesity because non-obese NAFLD might be a risk factor for sarcopenic obesity.

Associations of cardiovascular biomarkers and plasma albumin with exceptional survival to the highest ages.

Supercentenarians (those aged ≥110 years) are approaching the current human longevity limit by preventing or surviving major illness. Identifying specific biomarkers conducive to exceptional survival might provide insights into counter-regulatory mechanisms against aging-related disease. Here, we report associations between cardiovascular disease-related biomarkers and survival to the highest ages using a unique dataset of 1,427 oldest individuals from three longitudinal cohort studies, including 36 supercentenarians, 572 semi-supercentenarians (105-109 years), 288 centenarians (100-104 years), and 531 very old people (85-99 years). During follow-up, 1,000 participants (70.1%) died. Overall, N-terminal pro-B-type natriuretic peptide (NT-proBNP), interleukin-6, cystatin C and cholinesterase are associated with all-cause mortality independent of traditional cardiovascular risk factors and plasma albumin. Of these, low NT-proBNP levels are statistically associated with a survival advantage to supercentenarian age. Only low albumin is associated with high mortality across age groups. These findings expand our knowledge on the biology of human longevity.