Details of a Researcher - Arai, Yasumichi

Papers - Arai, Yasumichi

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Cardiovascular health and cognitive functioning among centenarians: A comparison between the Tokyo and Georgia centenarian studies

Martin P., Gondo Y., Arai Y., Ishioka Y., Johnson M., Miller L., Woodard J., Poon L., Hirose N.

International Psychogeriatrics (International Psychogeriatrics) 31 ( 4 ) 455 - 465 2019.04

ISSN 10416102

© International Psychogeriatric Association 2019. Objectives: Centenarians have survived into very late life, but whether they reach very old age in good health remains unclear. The purpose of this study was to compare the cardiovascular health status and cognitive functioning of centenarians in the United States with centenarians in Japan.Design, Setting, and Participants: This cross-national design compared centenarians from the United States and Japan. The sample of U.S. centenarians was recruited from the Georgia Centenarian Study and included 287 centenarians. The sample of Japanese centenarians was recruited from the Tokyo Centenarian Study and included 304 centenarians.Measurements: Cognitive functioning was assessed with a mental status questionnaire, and cardiovascular disease by a health history assessment, blood pressure, and selected blood parameters.Results: The results suggest that Tokyo centenarians had lower disease experiences and BMI values, when compared to Georgia centenarians, but blood pressure was higher among Japanese centenarians. Lower levels of hemoglobin in Japanese centenarians and higher levels of C-reactive protein in Georgia were also found. The positive association of hypertension and albumin levels with cognitive functioning and the negative association of stroke occurrence with cognitive functioning were replicated in both countries. Differential effects were obtained for heart problems, BMI, and C-reactive protein (with positive effects for Tokyo centenarians, except for C-reactive protein).Conclusion: For extremely old individuals, some markers of cardiovascular disease are replicable across countries, whereas differential effects for cardiovascular health also need to be considered in cardiovascular health.

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Subiculum volumes associated with memory function in the oldest-old individuals aged 95 years and older

Eguchi Y., Noda Y., Nakajima S., Tsugawa S., Kida H., Plitman E., Graff-Guerrero A., Chakravarty M., Takayama M., Arai Y., Matsuda H., Mimura M., Niimura H.

Geriatrics and Gerontology International (Geriatrics and Gerontology International) 19 ( 4 ) 347 - 351 2019.04

ISSN 14441586

© 2019 Japan Geriatrics Society Aim: Few cohort studies targeting the oldest-old individuals have been carried out. The subiculum in the hippocampus is thought to be related to memory function, and atrophy of this structure might result in the conversion from amnestic mild cognitive impairment to Alzheimer's disease. Thus, we sought to examine the relationship between subiculum volumes and memory function in individuals aged ≥95 years, using a novel cognitive examination called the Addenbrooke's Cognitive Examination III (ACE-III) and an advanced magnetic resonance imaging analytical method, Multiple Automatically Generated Templates Brain Segmentation Algorithm (MAGeTbrain), to measure hippocampal subfield volumes. Methods: A part of the cohort data of the Arakawa 95+ study for the oldest-old aged ≥95 years was used. A total of 10 individuals completed all of the examinations. The MAGeT brain was applied to estimate the subfield volumes of the hippocampus. Correlation analyses and multiple regression analyses were carried out to examine a relationship among ACE-III memory scores and the subfield volumes in the hippocampus, including the subiculum. Results: There was a significant relationship between ACE-III memory scores and subdivision volumes. Regression analyses showed that subiculum volumes were associated with ACE-III memory scores in the oldest-old individuals (β = 0.721, P = 0.019; F 1, 8 = 8.67, adjusted R 2 = 0.46). Conclusions: The subiculum might play a pivotal role in memory function in the oldest-old individuals aged ≥95 years. The present finding warrants further research including larger sample sizes. Geriatr Gerontol Int 2019; 19: 347–351.

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Association between long-term care and chronic and lifestyle-related disease modified by social profiles in community-dwelling people aged 80 and 90; SONIC study

Kiyoshige E., Kabayama M., Gondo Y., Masui Y., Ryuno H., Sawayama Y., Inoue T., Akagi Y., Sekiguchi T., Tanaka K., Nakagawa T., Yasumoto S., Ogawa M., Inagaki H., Oguro R., Sugimoto K., Akasaka H., Yamamoto K., Takeya Y., Takami Y., Itoh N., Takeda M., Nagasawa M., Yokoyama S., Maeda S., Ikebe K., Arai Y., Ishizaki T., Rakugi H., Kamide K.

Archives of Gerontology and Geriatrics (Archives of Gerontology and Geriatrics) 81 176 - 181 2019.03

ISSN 01674943

© 2018 Elsevier B.V. Background: Chronic and lifestyle-related diseases and social status were reported to be associated with long-term care (LTC). The social factors should be treated as social sub-groups of which characteristics show social profiles. However, few previous studies considered that. The present study aimed to investigate the associations between LTC and chronic and lifestyle-related diseases, and whether the associations were modified by the social sub-groups in the community-dwelling elderly. Method: A cross-sectional study was conducted among 1004 community-dwelling participants aged 80 and 90. LTC was used as the outcome. Chronic and lifestyle-related diseases (i.e., stroke, heart disease, joint pain, osteoporosis, lung disease, cancer, hypertension, dyslipidemia, and diabetes) were used as the predictors. Education, household income, residential area, and support environment were analyzed by latent class analysis (LCA) to derive social profiles. We obtained odds ratios (ORs) of LTC from those diseases and tested interactions between those diseases and the social profiles by logistic regression analyses. Result: The participants were categorized into two sub-groups of social factors (n = 675 and 329) by LCA. Logistic regression analyses showed ORs (95% CI) of LTC were 4.69 (2.49, 8.71) from stroke, 2.22 (1.46, 3.38) from joint pain, 1.99 (1.22, 3.25) from osteoporosis, and 2.05 (1.22, 3.40) from cancer adjusting for the social sub-groups. There were no significant interactions between the social subgroups and those diseases in relation to LTC except for osteoporosis. Conclusion: The associations between LTC and chronic and lifestyle-related diseases were significant with adjusting for the social sub-groups, and not modified by that except osteoporosis.

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

Kobayashi S., Yuan X., Sasaki S., Osawa Y., Hirata T., Abe Y., Takayama M., Arai Y., Masui Y., Ishizaki T.

Public Health Nutrition (Public Health Nutrition) 22 ( 2 ) 212 - 222 2019.02

ISSN 13689800

© The Authors 2018. 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.

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Hardness of the habitual diet and its relationship with cognitive function among 70-year-old Japanese elderly: Findings from the SONIC Study

Okubo H., Murakami K., Inagaki H., Gondo Y., Ikebe K., Kamide K., Masui Y., Arai Y., Ishizaki T., Sasaki S., Nakagawa T., Kabayama M., Sugimoto K., Rakugi H., Maeda Y., Ogawa M., Ishioka Y., Inomatae C., Ogawa T., Matsuda K., Ryuno H., Oguro R., Yamamoto K., Takeya Y., Takami Y., Ito N.

Journal of Oral Rehabilitation (Journal of Oral Rehabilitation) 46 ( 2 ) 151 - 160 2019.02

ISSN 0305182X

© 2018 John Wiley & Sons Ltd Background: There is increasing evidence of causal links between poor mastication and cognitive impairment, but possible effects of dietary hardness, which clearly affects mastication, on cognitive function are unknown. Objective: We investigated the hypothesis that hardness of the habitual diet would be associated with cognitive function among older Japanese adults. Methods: The subjects of this cross-sectional study were 635 Japanese community-dwelling people aged 69-71 years. The masticatory muscle activity required for the habitual diet was used to determine dietary hardness. Consumption of 38 foods was assessed by a validated, brief-type, self-administered diet history questionnaire. A published database was then used to estimate the masticatory muscle activity involved in the ingestion of these foods. The Japanese version of the Montreal Cognitive Assessment (MoCA-J) was used for the measurement of cognitive function. Results: The principal contributors to dietary hardness were cooked rice (28.0%), green leafy vegetables (5.1%), dried fish (4.9%), and pork and beef (4.6%). There was a positive association between dietary hardness and MoCA-J score that was robust to adjustment for potential confounders (MoCA-J score per 100-unit increase in dietary hardness: β = 0.83 [95% CI: 0.08, 1.59], P = 0.03). These results did not change materially even after exclusion of subjects who reported substantial changes in their diet for any reason (β = 0.94 [95% CI: 0.02, 1.86], P = 0.04). Conclusion: This preliminary cross-sectional study suggests that dietary hardness might have a beneficial effect on cognitive function in older Japanese people. Further prospective studies with more accurate measurements are needed to confirm this finding.

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Impact of cognitive function on oral perception in independently living older people

Fukutake M., Ogawa T., Ikebe K., Mihara Y., Inomata C., Takeshita H., Matsuda K., Hatta K., Gondo Y., Masui Y., Inagaki H., Arai Y., Kamide K., Ishizaki T., Maeda Y.

Clinical Oral Investigations (Clinical Oral Investigations) 23 ( 1 ) 267 - 271 2019.01

ISSN 14326981

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Objectives: Oral tactile perception is important for better mastication, appetite, and enjoyment of food. However, previous investigations have not utilized comprehensible variables thought to have negative effect on oral perception, including aging, denture wearing, and cognitive function. The aim of this study was to elucidate the impact of cognitive function on oral perception in independently living older individuals. Materials and methods: The study sample was comprised of 987 participants (466 males, 521 females; age 69–71 years). Oral examinations, assessments of cognitive function in preclinical level by Montreal Cognitive Assessment (MoCA)-J, and determination of oral stereognostic ability as an indicator of oral perception were performed. Related variables were selected by univariate analyses; then, multivariate logistic regression model analysis was conducted. Results: Univariate analyses revealed that number of teeth, removable dentures usage, and cognitive function respectively had a significant relationship with stereognostic score. Next, the subjects were classified into good and poor perception groups (lowest 17.4%) according to oral stereognostic ability. Logistic regression analysis revealed that lower cognitive function was significantly associated with poor oral perception (OR = 0.934, p = 0.017) after controlling for other variables. Conclusions: Cognitive decline even in preclinical stage was associated with reduced oral perception after controlling for gender, tooth number and denture use in independent living older people. Clinical relevance: This study suggested that preclinical level of change in cognitive function affected oral perception. Dental practitioners and caregivers may need to pay attention to reduced oral perception among older people even if they do not have trouble in daily life.

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APOE Alleles and extreme human longevity

Sebastiani P., Gurinovich A., Nygaard M., Sasaki T., Sweigart B., Bae H., Andersen S., Villa F., Atzmon G., Christensen K., Arai Y., Barzilai N., Puca A., Christiansen L., Hirose N., Perls T.

Journals of Gerontology - Series A Biological Sciences and Medical Sciences (Journals of Gerontology - Series A Biological Sciences and Medical Sciences) 74 ( 1 ) 44 - 51 2019.01

ISSN 10795006

© 2018 The Author(s). Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. We assembled a collection of 28,297 participants from seven studies of longevity and healthy aging comprising New England Centenarian, Long Life Family, Longevity Gene Population, Southern Italian Centenarian, Japanese Centenarian, the Danish Longevity, and the Health and Retirement Studies to investigate the association between the APOE alleles ϵ 2 ϵ 3 and ϵ 4 and extreme human longevity and age at death. By using three different genetic models and two definitions of extreme longevity based on either a threshold model or age at death, we show that ϵ 4 is associated with a substantially decreased odds for extreme longevity, and increased risk for death that persists even beyond ages reached by less than 1% of the population. We also show that carrying the ϵ 2 ϵ 2 or ϵ 2 ϵ 3 genotype is associated with significantly increased odds to reach extreme longevity, with decreased risk for death compared with carrying the genotype ϵ 3 ϵ 3 but with only a modest reduction in risk for death beyond an age reached by less than 1% of the population.

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Relationship between oral stereognostic ability and dietary intake in older Japanese adults with complete dentures

Fukutake M., Ikebe K., Okubo H., Matsuda K., Enoki K., Inomata C., Takeshita H., Mihara Y., Hatta K., Gondo Y., Kamide K., Masui Y., Ishizaki T., Arai Y., Maeda Y.

Journal of Prosthodontic Research (Journal of Prosthodontic Research) 63 ( 1 ) 105 - 109 2019.01

ISSN 18831958

© 2018 Japan Prosthodontic Society Purpose: Oral stereognostic ability (OSA) is a useful indicator of oral perception to recognize food characteristics during mastication. Previous studies have shown associations between dietary intake and oral health status, such as taste perception. However, the effect of oral sensory ability on dietary intake is unclear. The purpose of this study was to investigate the association between oral sensory ability and dietary intake in older Japanese complete denture wearers. Methods: This cross-sectional study included 164 participants aged 69–71 or 79–81 years old, wearing both maxillary and mandibular complete dentures. OSA test was used to evaluate oral tactile perception. Diet during the preceding month was assessed using a self-administered diet history questionnaire. Multivariable linear regression analysis was conducted to assess the association between OSA score and food and nutrient intake after adjusting for age, sex, socioeconomic factors, and occlusal force. Results: The bivariate analysis showed that OSA score was significantly and positively correlated with intake of green and yellow vegetables and negatively correlated with intake of cereals among examined foods. OSA score was also positively correlated with intake of vitamins A, B 2 , and C and α-tocopherol (as a substitute for vitamin E) among examined nutrients. After adjusting for age, sex, socioeconomic factors, and occlusal force, OSA score remained significantly associated with intake of green and yellow vegetables and α-tocopherol. Conclusions: OSA was significantly associated with intake of green and yellow vegetables in older complete denture wearers.

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Lack of posterior occlusal support predicts the reduction in walking speed in 80-year-old Japanese adults: A 3-year prospective cohort study with propensity score analysis by the SONIC Study Group

Hatta K., Ikebe K., Mihara Y., Gondo Y., Kamide K., Masui Y., Sugimoto K., Matsuda K., Fukutake M., Kabayama M., Shintani A., Ishizaki T., Arai Y., Rakugi H., Maeda Y.

Gerodontology (Gerodontology) 36 ( 2 ) 156 - 162 2019

ISSN 07340664

© 2019 Gerodontology Association and John Wiley & Sons Ltd Objective: To investigate the association between posterior occlusal support by residual teeth and the reduction in walking speed in 80-year-old Japanese adults using propensity score matching. Background data discussing the present status of the field: Previous studies have demonstrated an association between oral status and motor function; however, most of these studies had a cross-sectional design. Material and method: This study included 353 community-dwelling Japanese people aged 79-81 years. Low walking speed was defined as ≤0.8 m/s, and participants with a low walking speed at baseline were excluded. The participants were divided into two groups: with or without posterior occlusal support by residual teeth at baseline. Propensity score matching was used to reduce the effects of bias by matching participants with and without posterior occlusal support according to similar background factors at baseline. Conditional logistic regression was conducted to determine low walking speed at the 3-year follow-up, which included posterior occlusal support as an independent variable with matching data. Results: Before matching for posterior occlusal support, significant differences existed between the groups in terms of sex, years of education, height, weight and grip strength. However, after matching, there was no significant difference between the groups in any characteristic. Logistic regression analysis showed that posterior occlusal support is a significant variable (odds ratio = 1.88; P = 0.04) associated with reduced walking speed. Conclusion: Lack of posterior occlusal support at baseline independently predicted the incidence of reduced walking speed over 3 years.

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Serum albumin/globulin ratio is associated with cognitive function in community-dwelling older people: The Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study

Maeda S., Takeya Y., Oguro R., Akasaka H., Ryuno H., Kabayama M., Yokoyama S., Nagasawa M., Fujimoto T., Takeda M., Onishi-Takeya M., Itoh N., Takami Y., Yamamoto K., Sugimoto K., Inagaki H., Ogawa M., Nakagawa T., Yasumoto S., Masui Y., Arai Y., Ishizaki T., Ikebe K., Gondo Y., Kamide K., Rakugi H.

Geriatrics and Gerontology International (Geriatrics and Gerontology International) 2019

ISSN 14441586

© 2019 Japan Geriatrics Society Aim: The objective of this study was to clarify the relationship between cognitive function and the serum albumin/globulin ratio (A/G ratio) in community-dwelling Japanese older adults. Methods: Randomly extracted residents in both urban and rural parts of Japan were enrolled in this study. A total of 1827 participants with a mean age of 70 or 80 years were recruited. A venue survey method was carried out with comprehensive studies, including interviews, blood collection, physical examination and cognitive function tests. Results: Univariate analysis showed a significant positive correlation between the total Japanese version of the Montreal Cognitive Assessment score and the serum A/G ratio at the age of 70 and 80 years, in which better cognitive function was associated with a high serum A/G ratio. Multiple regression analysis with the total Japanese version of the Montreal Cognitive Assessment score as the dependent variable showed that the serum albumin level, serum globulin level, serum A/G ratio, C-reactive protein, years of formal education and sex were related to the Japanese version of the Montreal Cognitive Assessment total score at the age of 70 years, and that the serum albumin level, serum globulin level, serum A/G ratio, C-reactive protein, years of formal education and stroke were related at the age of 80 years. The serum A/G ratio showed a better correlation than the serum globulin levels at the age of 70 and 80 years (70 years: β = 0.131 vs –0.111, 80 years: β = 0.108 vs –0.071). Conclusions: We found a correlation between cognitive function and the serum A/G ratio in community-dwelling older people, suggesting that nutritional status and chronic inflammation might influence cognitive function. Geriatr Gerontol Int 2019; ••: ••–••.

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Adipokines and aging: Findings from centenarians and the very old

Arai Y., Kamide K., Hirose N.

Frontiers in Endocrinology (Frontiers in Endocrinology) 10 ( MAR ) 2019

© 2019 Arai, Kamide and Hirose. Adipose tissue, which was once considered as a simple energy storage depot, is now recognized as an active endocrine organ that regulates the whole-body energy homeostasis by secreting hundreds of bioactive substances termed adipokines. Dysregulation of adipokines is a key feature of insulin resistance and a metabolic syndrome associated with obesity. Adipokine dysregulation and insulin resistance are also associated with energy-deprivation conditions, such as frailty in old age. Previous studies have demonstrated that preserved insulin sensitivity and low prevalence of diabetes are the metabolic peculiarities of centenarians, suggesting the possible role of adipokine homeostasis in healthy longevity. Among the numerous adipokines, adiponectin is regarded as unique and salutary, showing negative correlations with several age- and obesity-related metabolic disturbances and a positive correlation with longevity and insulin sensitivity among centenarians. However, large-scale epidemiological studies have implied the opposite aspect of this adipokine as a prognostic factor for all-cause and cardiovascular mortality in patients with heart failure or kidney disease. In this review, the clinical significance of adiponectin was comparatively addressed in centenarians and the very old, in terms of frailty, cardiovascular risk, and mortality.

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Deep whole-genome sequencing reveals recent selection signatures linked to evolution and disease risk of Japanese

Okada Y., Momozawa Y., Sakaue S., Kanai M., Ishigaki K., Akiyama M., Kishikawa T., Arai Y., Sasaki T., Kosaki K., Suematsu M., Matsuda K., Yamamoto K., Kubo M., Hirose N., Kamatani Y.

Nature Communications (Nature Communications) 9 ( 1 ) 2018.12

© 2018 The Author(s). Understanding natural selection is crucial to unveiling evolution of modern humans. Here, we report natural selection signatures in the Japanese population using 2234 high-depth whole-genome sequence (WGS) data (25.9×). Using rare singletons, we identify signals of very recent selection for the past 2000-3000 years in multiple loci (ADH cluster, MHC region, BRAP-ALDH2, SERHL2). In large-scale genome-wide association study (GWAS) dataset (n = 171,176), variants with selection signatures show enrichment in heterogeneity of derived allele frequency spectra among the geographic regions of Japan, highlighted by two major regional clusters (Hondo and Ryukyu). While the selection signatures do not show enrichment in archaic hominin-derived genome sequences, they overlap with the SNPs associated with the modern human traits. The strongest overlaps are observed for the alcohol or nutrition metabolism-related traits. Our study illustrates the value of high-depth WGS to understand evolution and their relationship with disease risk.

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Physical, sensory, and cognitive functioning among centenarians: a comparison between the Tokyo and Georgia centenarian studies

Martin P., Gondo Y., Arai Y., Ishioka Y., Woodard J., Poon L., Hirose N.

Quality of Life Research (Quality of Life Research) 27 ( 11 ) 3037 - 3046 2018.11

ISSN 09629343

© 2018, Springer Nature Switzerland AG. Purpose: The purpose of this study was to compare centenarians in the United States and Japan on sensory, cognitive, and physical functioning and to evaluate a model that tests the interrelationship between physical function, cognition, and sensory impairment in these two unique samples of the oldest old. Methods: The sample of U. S. centenarians included 245 centenarians, the sample of Japanese centenarians included 304 centenarians. Sensory impairment was assessed by general assessments of vision and hearing, and physical function was assessed with six physical activities of daily living (i.e., eating, grooming, dressing, transporting, bathing, and walking). Results: The results suggest that centenarians from the Georgia study showed higher levels of functioning in all domains when compared to the Tokyo sample. A structural equation model yielded stronger associations between cognitive and sensory function with physical function for the Tokyo sample. Conclusions: Functional differences may be due, in part, to different care patterns for the oldest old in the United States when compared to Japan.

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Relationship between gerotranscendence and oral health-related quality of life

Mihara Y., Matsuda K., Hatta K., Gondo Y., Masui Y., Nakagawa T., Kamide K., Ishizaki T., Arai Y., Maeda Y., Ikebe K.

Journal of Oral Rehabilitation (Journal of Oral Rehabilitation) 45 ( 10 ) 805 - 809 2018.10

ISSN 0305182X

© 2018 John Wiley & Sons Ltd Objectives: The purpose of our cross-sectional study was to investigate the relationship between gerotranscendence and oral health-related quality of life (OHR-QOL). To our knowledge, this is the first study to investigate the relationship between gerotranscendence and OHR-QOL. Methods: Participants (total n = 1969; 70-year-old group, n = 999; 80-year-old group, n = 970) were drawn from resident lists in four areas of Japan: one urban area and one rural area in each of two geographical regions. OHR-QOL was measured using the Geriatric Oral Health Assessment Index (GOHAI). Measurement of occlusal force was performed using pressure-sensitive sheets. Gerotranscendence was assessed with the Japanese Gerotranscendence Scale Revised (JGS-R). We used multiple linear regression analysis to examine the relationships among OHR-QOL and other variables. Results: Geriatric Oral Health Assessment Index score was significantly correlated with occlusal force, number of teeth, financial status and JGS-R score on linear regression analysis. Conclusion: Degree of gerotranscendence was significantly and independently correlated with degree of OHR-QOL in our sample.

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Influence of lack of posterior occlusal support on cognitive decline among 80-year-old Japanese people in a 3-year prospective study

Hatta K., Ikebe K., Gondo Y., Kamide K., Masui Y., Inagaki H., Nakagawa T., Matsuda K., Ogawa T., Inomata C., Takeshita H., Mihara Y., Fukutake M., Kitamura M., Murakami S., Kabayama M., Ishizaki T., Arai Y., Sugimoto K., Rakugi H., Maeda Y.

Geriatrics and Gerontology International (Geriatrics and Gerontology International) 18 ( 10 ) 1439 - 1446 2018.10

ISSN 14441586

© 2018 Japan Geriatrics Society Aim: Previous studies have reported significant associations between tooth loss or periodontal status and cognitive function; however, animal experimental studies have shown that occlusion might be a more important factor in cognitive decline. The purpose of the present study was to investigate the influence of a lack of posterior occlusal support by residual teeth on the decline of cognitive function over a 3-year period among 80-year-old Japanese people. Methods: Participants were community-dwelling older adults (n = 515, age 79–81 years). Cognitive function was measured using the Japanese version of the Montreal Cognitive Assessment. At baseline, participants were divided into two groups: those with and without posterior occlusal support. Participants whose Japanese version of the Montreal Cognitive Assessment score decreased by ≥3 points over the 3-year period were defined as the declined group. Logistic regression was carried out for the decline in Japanese version of the Montreal Cognitive Assessment scores, including dental status and possible risk factors as independent variables. Results: More participants without posterior occlusal support tended to be in the cognitive decline group (49.4%) than in the maintained group (38.5%; χ2-test, P = 0.02). Logistic regression analysis showed that a lack of posterior occlusal support was a significant variable (odds ratio 1.55, P = 0.03) for cognitive decline, even after adjusting for other risk factors. However, the number of teeth or mean periodontal pocket depth was not significantly correlated with cognitive decline. Conclusions: The present findings suggest that a lack of posterior occlusal support predicted the incidence of cognitive decline, even after adjusting for possible risk factors in community-dwelling old-old people. Geriatr Gerontol Int 2018; 18: 1439–1446.

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Increased oxidative stress and coenzyme Q10 deficiency in centenarians

Nagase M., Yamamoto Y., Matsumoto N., Arai Y., Hirose N.

Journal of Clinical Biochemistry and Nutrition (Journal of Clinical Biochemistry and Nutrition) 63 ( 2 ) 129 - 136 2018.09

ISSN 09120009

©2018 JCBN. Aging populations are expanding worldwide, and the increasing requirement for nursing care has become a serious problem. Furthermore, successful aging is one of the highest priorities for individuals and societies. Centenarians are an informative cohort to study and inflammation has been found to be a key factor in predicting cognition and physical capabilities. Inflammation scores have been determined based on the levels of cytokines and C reactive protein, however, serum antioxidants and lipid profiles have not been carefully examined. We found that the redox balance of coenzyme Q10 significantly shifted to the oxidized form and levels of strong antioxidants, such as ascorbic acid and unconjugated bilirubin, decreased significantly compared to 76 yearold controls, indicating an increased oxidative stress in centenarians. Levels of uric acid, an endogenous peroxynitrite scavenger, remained unchanged, suggesting that centenarians were experiencing moderate, chronic inflammatory conditions. Centenarians exhibited a hypocholesterolemic condition, while an increase in the ratio of free cholesterol to cholesterol esters sug gests some impairment of liver function. Serum free fatty acids and monoenoic acid composition, markers of tissue oxidative damage, were significantly decreased in centenarians, indicating an impairment in the tissue repair system. Despite an elevation of the coenzyme Q10 binding protein Psap, serum total coenzyme Q10 levels decreased in centenarians. This suggests a serious deficiency of coenzyme Q10 in tissues, since tissue levels of coenzyme Q10 significantly decrease with age. Therefore, coenzyme Q10 supple mentation could be beneficial for centenarians.

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Association of handgrip strength with various oral functions in 82- to 84-year-old community-dwelling Japanese

Mihara Y., Matsuda K., Ikebe K., Hatta K., Fukutake M., Enoki K., Ogawa T., Takeshita H., Inomata C., Gondo Y., Masui Y., Kamide K., Sugimoto K., Kabayama M., Ishizaki T., Arai Y., Maeda Y.

Gerodontology (Gerodontology) 35 ( 3 ) 214 - 220 2018.09

ISSN 07340664

© 2018 Gerodontology Association and John Wiley & Sons Ltd Objective: The purpose of this study was to elucidate the associations between muscle strength and several oral functions in a large cohort of community-dwelling, 82- to 84-year-old community-dwelling Japanese people. Background data discussing the present status of the field: Several studies have examined the relationships between physical performance and oral functions. However, no studies have investigated the associations of muscle strength with various objectively evaluated oral functional parameters in a large cohort of very old adults. Materials and Methods: This study included 809 community-dwelling Japanese people (407 men and 402 women) aged 82-84 years. The oral functions examined were the maximal occlusal force, masticatory performance, stimulated salivary flow rate, repetitive saliva-swallowing test (RSST) score, tongue pressure and mouth-opening distance. Handgrip strength was measured, and its correlations with oral functions were assessed. Multiple linear and logistic regression analyses were performed to investigate the relationships between oral functions and handgrip strength. Results: Multivariate analysis revealed that handgrip strength was correlated with not only the maximal occlusal force, masticatory performance and tongue pressure but also the RSST score and mouth-opening distance after adjustment for sex, number of teeth, use of removable denture, periodontal condition, instrumental activities of daily living, body mass index. When we examine the elderly people whose handgrip strength is declining, we should predict that their various oral functions may be declining. Conclusion: Handgrip strength was related to various oral functions after adjustment for the number of teeth in this population of community-dwelling 82- to 84-year-old Japanese.

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Relationships between socio-clinico-demographic factors and global cognitive function in the oldest old living in the Tokyo Metropolitan area: Reanalysis of the Tokyo Oldest Old Survey on Total Health (TOOTH)

Eguchi Y., Tasato K., Nakajima S., Noda Y., Tsugawa S., Shinagawa S., Niimura H., Hirose N., Arai Y., Mimura M.

International Journal of Geriatric Psychiatry (International Journal of Geriatric Psychiatry) 33 ( 7 ) 926 - 933 2018.07

ISSN 08856230

Copyright © 2018 John Wiley & Sons, Ltd. Background: Despite a steady increase in life expectancy, a few studies have investigated cross-sectional correlates and longitudinal predictors of cognitive function, a core domain of the successful aging, among socio-clinico-demographic factors in the oldest-old exclusively. Objectives: The aims of this study were to examine socio-clinico-demographic characteristics associated with global cognition and its changes in the oldest-old. Methods: We reanalyzed a dataset of cognitively preserved community-dwelling subjects aged 85 years and older in the Tokyo Oldest Old Survey on Total Health, a 6-year longitudinal observational study. This study consisted of (1) baseline cross-sectional analyses examining correlates of global cognition (n = 248) among socio-clinico-demographic factors and (2) longitudinal analyses examining baseline predictors for changes of global cognition in 3-year follow-up (n = 195). The Mini-Mental State Examination was used as a screening test to assess global cognition. Results: At baseline, higher weights were related to higher cognitive function in the oldest-old. The baseline predictors of global cognitive decline in 3-year follow-up were higher global cognition, shorter education period, and lower sociocultural activities and lower instrumental activity of daily living, in this order. Conclusions: The present study suggests that it is crucial to attain higher education during early life and avoid leanness or obesity, participate in sociocultural cognitive activities during late life, and maintain instrumental activity of daily living to preserve optimal cognitive function in the oldest-old, which will facilitate developing prevention strategies for cognitive decline and promoting successful aging in this increasing population.

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Characteristic glycopeptides associated with extreme human longevity identified through plasma glycoproteomics

Miura Y., Hashii N., Ohta Y., Itakura Y., Tsumoto H., Suzuki J., Takakura D., Abe Y., Arai Y., Toyoda M., Kawasaki N., Hirose N., Endo T.

Biochimica et Biophysica Acta - General Subjects (Biochimica et Biophysica Acta - General Subjects) 1862 ( 6 ) 1462 - 1471 2018.06

ISSN 03044165

© 2018 Elsevier B.V. Background: Glycosylation is highly susceptible to changes of the physiological conditions, and accordingly, is a potential biomarker associated with several diseases and/or longevity. Semi-supercentenarians (SSCs; older than 105 years) are thought to be a model of human longevity. Thus, we performed glycoproteomics using plasma samples of SSCs, and identified proteins and conjugated N-glycans that are characteristic of extreme human longevity. Methods: Plasma proteins from Japanese semi-supercentenarians (SSCs, 106–109 years), aged controls (70–88 years), and young controls (20–38 years) were analysed by using lectin microarrays and liquid chromatography/mass spectrometry (LC/MS). Peak area ratios of glycopeptides to corresponding normalising peptides were subjected to orthogonal projections to latent structures discriminant analysis (OPLS-DA). Furthermore, plasma levels of clinical biomarkers were measured. Results: We found two lectins such as Phaseolus vulgaris, and Erythrina cristagalli (ECA), of which protein binding were characteristically increased in SSCs. Peak area ratios of ECA-enriched glycopeptides were successfully discriminated between SSCs and controls using OPLS-DA, and indicated that tri-antennary and sialylated N-glycans of haptoglobin at Asn207 and Asn211 sites were characterized in SSCs. Sialylated glycans of haptoglobin are a potential biomarker of several diseases, such as hepatocellular carcinoma, liver cirrhosis, and IgA-nephritis. However, the SSCs analysed here did not suffer from these diseases. Conclusions: Tri-antennary and sialylated N-glycans on haptoglobin at the Asn207 and Asn211 sites were abundant in SSCs and characteristic of extreme human longevity. General significance: We found abundant glycans in SSCs, which may be associated with human longevity.

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High plasma adiponectin levels are associated with frailty in a general old-old population: The Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study

Nagasawa M., Takami Y., Akasaka H., Kabayama M., Maeda S., Yokoyama S., Fujimoto T., Nozato Y., Imaizumi Y., Takeda M., Itoh N., Takeya Y., Yamamoto K., Sugimoto K., Nakagawa T., Masui Y., Arai Y., Ishizaki T., Ikebe K., Gondo Y., Kamide K., Rakugi H.

Geriatrics and Gerontology International (Geriatrics and Gerontology International) 18 ( 6 ) 839 - 846 2018.06

ISSN 14441586

© 2018 Japan Geriatrics Society Aim: The objective of the present study was to investigate the association between frailty and plasma adiponectin levels in a general population of Japanese older adults. Methods: The volunteer older adults, aged approximately 83 years, were recruited randomly from a general population in the Japanese Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study. We used the modified Cardiovascular Health Study criteria to assess the frailty status of the study participants. The study participants were classified as non-frail, pre-frail and frail according to their physical activities. We compared plasma adiponectin levels among these three groups and applied a multivariate logistic regression analysis including plasma adiponectin levels to clarify the factors associated with frailty status in the cross-sectional design. Results: The mean age of the participants was 83.1 ± 0.9 years, and 51.8% were men. The frailty index was available to assess 353 participants, of whom 24.6% were classified as non-frail, 62.3% as prefrail and 13.0% as frail. The log-transformed plasma adiponectin levels increased stepwise in the following order: non-frail, pre-frail and frail. A multivariate logistic regression analysis showed that higher plasma adiponectin levels, a higher estimated glomerular filtration rate and lower hemoglobin levels were independent determinants for pre-frail/frail status compared with non-frail status. Conclusions: The present study showed that higher plasma adiponectin levels were associated with frailty status in older Japanese adults in the general population. Further longitudinal study is essential to clarify the role of plasma adiponectin in the progression of frailty. Geriatr Gerontol Int 2018; 18: 839–846.

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Inverse Association between Height-Increasing Alleles and Extreme Longevity in Japanese Women

Tanisawa K., Hirose N., Arai Y., Shimokata H., Yamada Y., Kawai H., Kojima M., Obuchi S., Hirano H., Suzuki H., Fujiwara Y., Taniguchi Y., Shinkai S., Ihara K., Sugaya M., Higuchi M., Arai T., Mori S., Sawabe M., Sato N., Muramatsu M., Tanaka M.

Journals of Gerontology - Series A Biological Sciences and Medical Sciences (Journals of Gerontology - Series A Biological Sciences and Medical Sciences) 73 ( 5 ) 588 - 595 2018.04

ISSN 10795006

© 2018 Oxford University Press. All rights reserved. Growth hormone (GH)/insulin-like growth factor-1 (IGF-1)/insulin signaling is one of the most plausible biological pathways regulating aging and longevity. Previous studies have demonstrated that several single nucleotide polymorphisms (SNPs) in the GH/IGF-1/insulin signaling-associated genes influence both longevity and adult height, suggesting the possibility of a shared genetic architecture between longevity and height. We therefore examined the relationship between 30 height-associated SNPs and extreme longevity in a Japanese population consisting of 428 centenarians and 4,026 younger controls. We confirmed that height-increasing genetic scores (HGSs) constructed based on 30 SNPs were significantly associated with height in the controls (p = 6.951023). HGS was significantly and inversely associated with extreme longevity in women (p = .011), but not in men, although no SNPs were significantly associated with extreme longevity after Bonferroni correction. The odds ratio for extreme longevity in the lowest HGS group (=27) and the second lowest HGS group (2830) relative to the highest HGS group (=37) was 1.71 (p = .056) and 1.69 (p = .034), respectively, for women. In conclusion, the present study demonstrated an inverse association between height-increasing alleles with extreme longevity in Japanese women, providing novel insight into the genetic architecture of longevity and aging.

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Occlusal force is correlated with cognitive function directly as well as indirectly via food intake in community-dwelling older Japanese: From the SONIC study

Ikebe K., Gondo Y., Kamide K., Masui Y., Ishizaki T., Arai Y., Inagaki H., Nakagawa T., Kabayama M., Ryuno H., Okubo H., Takeshita H., Inomata C., Kurushima Y., Mihara Y., Hatta K., Fukutake M., Enoki K., Ogawa T., Matsuda K., Sugimoto K., Oguro R., Takami Y., Itoh N., Takeya Y., Yamamoto K., Rakugi H., Murakami S., Kitamura M., Maeda Y.

PLoS ONE (PLoS ONE) 13 ( 1 ) 2018.01

© 2018 Ikebe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Growing evidence suggests that oral health may be an important factor associated with cognitive function in aged populations. However, many previous studies on this topic used insensitive oral indicators or did not include certain essential covariates. Thus, we examined the association between occlusal force and cognitive function in a large sample of older adults, controlling for dietary intake, vascular risk factors, inflammatory biomarkers, depression, and genetic factors. Methods In this cross-sectional study of older community-dwelling Japanese adults, we examined data collected from 994 persons aged 70 years and 968 persons aged 80 years. Cognitive function was measured using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Oral status and function were evaluated according to the number of remaining teeth, periodontal pocket depth, and maximal occlusal force. Associations between MoCA-J scores and occlusal force were investigated via bivariate and multivariate analyses. Results Education level, financial status, depression score, and intake of green and yellow vegetables, as well as number of teeth and occlusal force, were significantly correlated with MoCA-J scores in both age groups. Among individuals aged 80 years, CRP and periodontal status were weakly but significantly associated with MoCA-J score. After controlling for all significant variables via bivariate analyses, the correlation between maximal occlusal force and cognitive function persisted. A path analysis confirmed the hypothesis that cognitive function is associated with occlusal force directly as well as indirectly via food intake. Conclusions After controlling for possible factors, maximal occlusal force was positively associated with cognitive function directly as well as indirectly through dietary intake.

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Carotid plaque score and risk of cardiovascular mortality in the oldest old: Results from the TOOTH study

Hirata T., Arai Y., Takayama M., Abe Y., Ohkuma K., Takebayashi T.

Journal of Atherosclerosis and Thrombosis (Journal of Atherosclerosis and Thrombosis) 25 ( 1 ) 55 - 64 2018

ISSN 13403478

© 2018 Japan Atherosclerosis Society. Aim: Accumulating evidence suggests that predictability of traditional cardiovascular risk factors declines with advancing age. We investigated whether carotid plaque scores (CPSs) were associated with cardiovascular disease (CVD) death in the oldest old, and whether asymmetrical dimethylarginine (ADMA), a marker of endothelial dysfunction, moderated the association between the CPS and CVD death. Methods: We conducted a prospective cohort study of Japanese subjects aged ≥85 years without CVD at baseline. We followed this cohort for 6 years to investigate the association of CPS with CVD death via multivariable Cox proportional hazard analysis. We divided participants into three groups according to CPS (no, 0 points; low, 1.2–4.9 points; high, ≥5.0 points). The predictive value of CPS for estimating CVD death risk over CVD risk factors, including ADMA, was examined using C-statistics. Results: We analyzed 347 participants (151 men, 196 women; mean age, 87.6 years), of which 135 (38.9%) had no carotid plaque at baseline, and 48 (13.8%) had high CPS. Of the total, 29 (8.4%) participants experienced CVD-related death during the study period. Multivariable analysis revealed a significant association of high CPS with CVD-related mortality relative to no CPS (hazard ratio, 3.90; 95% confidence interval: 1.47–10.39). ADMA was not associated with CVD death, but the significant association between CPS and CVD death was observed only in lower ADMA level. The addition of CPS to other risk factors improved the predictability of CVD death (p=0.032). Conclusions: High CPS correlated significantly with a higher CVD death risk in the oldest old with low cardiovascular risk. Ultrasound carotid plaque evaluation might facilitate risk evaluations of CVD death in the very old.

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Deficiency of Choresteryl Ester Transfer Protein and Gene Polymorphisms of Lipoprotein Lipase and Hepatic Lipase are not associated with Longevity

Arai Y, Hirose N, Yamamura K, Nakazawa Susumu, Shimizu Kenichirou, Takayama Michiyo, Ebihara Yoshinori, Homma Satoshi, Gondo Yasuyuki, Masui Yukie, Inagaki Hiroki

Journal of molecular medicine 81 ( 1 ) 102 2003.01