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Individuals with mild cognitive impairment (MCI) often make qualitative errors on the Clock Drawing Test (CDT), and these errors are reported to be associated with lower scores on neuropsychological assessments. Gait speed is also closely associated with cognitive dysfunction. However, the association between CDT errors and gait speed has not been investigated in individuals with MCI. Therefore, in this study, we explored the association between gait speed and qualitative errors on the CDT. Participants were 196 outpatients at a memory clinic with a clinical dementia rating of 0.5. The CDT was evaluated using the method of Cahn et al. The participants were divided into tertiles of normal and maximum gait speeds. The CDT error types of stimulus-bound response, conceptual deficit (CD), and planning deficit were found in 24.5%, 29.6%, and 30.1% of the participants, respectively. CD was found in 43.6% of the slowest tertile of maximum gait and in 22.2% of the fastest tertile. Multiple linear regression analysis gait speeds as objective continuous variables revealed that CD was significantly negatively associated with maximum gait, but not with normal gait. No other error types were associated with gait speeds. Only CD type error on the CDT was negatively associated with maximum gait speed, but not normal gait speed in the current study. The association between the qualitative error on the CDT and gait speed provides further basis of the clinical importance of qualitative assessments of CDT., (© 2022. The Author(s).)

Objectives: Frailty is a state of increased vulnerability to poor resolution of homeostasis after a stressor. We hypothesized that frail older adults would tend to have electrolyte imbalances because they should have many stressors together with fragile physiological systems. In this study, we aimed to determine whether older adults with higher Frailty Index scores have electrolyte imbalances and to establish which domains of the Frailty Index are correlated with electrolyte imbalances., Design: A cross-sectional study., Setting and Participants: A total of 4204 older adults aged 70 years or over who visited the Japanese National Center for Geriatrics and Gerontology., Methods: We calculated the 50-item Frailty Index with the following domains: comorbidities, cognitive function and mood, basic and instrumental activities of daily living, physical function, nutrition, and fall risks from physical weakness and comorbidities. Participants were categorized into four groups: a non-frail group (Frailty Index ≤0.2), mildly frail group (0.20 < Frailty Index ≤0.3), moderately frail group (0.3 < Frailty Index ≤0.4), and severely frail group (0.4 < Frailty Index). Their serum sodium, potassium, calcium, and phosphorus concentrations were measured. A multiple regression model was used to explore the relationship of electrolyte imbalances with the Frailty Index and to determine which frailty domains are correlated with electrolyte imbalances., Results: Compared with the non-frail group, the mildly and moderately frail groups tended to have hypernatremia and hypophosphatemia, whereas the severely frail group tended to have dysnatremia, hypokalemia, and hypophosphatemia. The estimated odds ratios increased by 15%-52% for each electrolyte imbalance as the Frailty Index increased by 0.1. The Frailty Index domains of cognitive function, activities of daily living, and nutrition were correlated with more than three kinds of electrolyte imbalances, the domains of physical function and fall risks from physical weakness were correlated with three kinds of electrolyte imbalances, and the domains of comorbidities and fall risks from comorbidities were correlated with two kinds of electrolyte imbalances., Conclusions: Older adults with higher Frailty Index scores tend to have electrolyte imbalances., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Skeletal muscle mass and function losses in aging individuals are associated with quality of life deterioration and disability. Mesenchymal stromal cells exert immunomodulatory and anti-inflammatory effects and could yield beneficial effects in aging-related degenerative disease., Methods and Results: We investigated the efficacy of umbilical cord-derived mesenchymal stromal cells (UC-MSCs) on sarcopenia-related skeletal muscle atrophy and dysfunction in senescence-accelerated mouse prone 10 (SAMP10) mice. We randomly assigned 24-week-old male SAMP10 mice to a UC-MSC treatment group and control group. At 12 weeks post-injection, the UC-MSC treatment had ameliorated sarcopenia-related muscle changes in performance, morphological structures, and mitochondria biogenesis, and it enhanced the amounts of proteins or mRNAs for myosin heavy chain, phospho-AMP-activated protein kinase, phospho-mammalian target of rapamycin, phospho-extracellular signal-regulated kinase1/2, peroxisome proliferator-activated receptor-γ coactivator, GLUT-4, COX-IV, and hepatocyte growth factor in both gastrocnemius and soleus muscles, and it reduced the levels of proteins or mRNAs for cathepsin K, cleaved caspase-3/-8, tumor necrosis factor-α, monocyte chemoattractant protein-1, and gp91 phox mRNAs. The UC-MSC treatment retarded mitochondria damage, cell apoptosis, and macrophage infiltrations, and it enhanced desmin/laminin expression and proliferating and CD34 + /Integrin α 7 + cells in both types of skeletal muscle of the SAMP10 mice. In vitro, we observed increased levels of HGF, PAX-7, and MoyD mRNAs at the 4th passage of UC-MSCs., Conclusions: Our results suggest that UC-MSCs can improve sarcopenia-related skeletal muscle atrophy and dysfunction via anti-apoptosis, anti-inflammatory, and mitochondrial biogenesis mechanisms that might be mediated by an AMPK-PGC1-α axis, indicating that UC-MSCs may provide a promising treatment for sarcopenia/muscle diseases., (© 2022. The Author(s).)

Werner syndrome (WS) is a progeroid syndrome caused by mutations in the WRN gene, which encodes the RecQ type DNA helicase for the unwinding of unusual DNA structures and is implicated in DNA replication, DNA repair, and telomere maintenance. patients with WS are prone to develop malignant neoplasms, including hematological malignancies. However, the pathogenesis of WS-associated hematological malignancies remains uncharacterized. Here we investigated the somatic gene mutations in WS-associated myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). Whole-exome sequencing (WES) of 4 patients with WS with MDS/AML revealed that all patients had somatic mutations in TP53 but no other recurrent mutations in MDS/AML. TP53 mutations were identified at low allele frequencies at more than one year before the MDS/AML stage. All 4 patients had complex chromosomal abnormalities including those that involved TP53. Targeted sequencing of nine patients with WS without apparent blood abnormalities did not detect recurrent mutations in MDS/AML except for a PPM1D mutation. These results suggest that patients with WS are apt to acquire TP53 mutations and/or chromosomal abnormalities involving TP53, rather than other MDS/AML-related mutations. TP53 mutations are frequently associated with prior exposure to chemotherapy; however, all four patients with WS with TP53 mutations/deletions had not received any prior chemotherapy, suggesting a pathogenic link between WRN mutations and p53 insufficiency. These results indicate that WS hematopoietic stem cells with WRN insufficiency acquire competitive fitness by inactivating p53, which may cause complex chromosomal abnormalities and the subsequent development of myeloid malignancies. These findings promote our understanding of the pathogenesis of myeloid malignancies associated with progeria., (Copyright © 2022 ISEH -- Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)

To treat older patients with hypertension, it is important to detect cognitive impairment at an early stage because of its potential influence on treatment efficacy and functional prognosis. In this study, we aimed to identify the incidence and determinants of cognitive impairment in hypertensive patients aged 65 years and above who visited our outpatient clinic and were not previously diagnosed with cognitive impairment. Among 312 patients with hypertension, we found that 35% (n = 109) and 7.7% (n = 24) had cognitive impairment and dementia, respectively, as defined by the Mini-Mental State Examination (≤27 or ≤23, respectively). Patients with cognitive impairment were older, had lower levels of education, and had lower instrumental activities of daily living (IADL) scores than those without cognitive impairment. Multiple regression analysis revealed that age and IADL were associated with cognitive impairment in patients with hypertension. Regarding the treatment of hypertension, the office and home blood pressure levels, number of antihypertensive medications prescribed, and proportion of the use of each antihypertensive drug was equivalent between patients with and without cognitive impairment. Finally, patients with unrecognized cognitive impairment showed distinct clinical characteristics, including high antihypertensive medication burden and preserved IADL, when compared to hypertensive patients in the different cohorts of definitive mild cognitive impairment of a similar age. These findings suggest that older hypertensive patients are at a high risk of masked cognitive decline, even if they are functionally independent., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Cachexia is a complicated metabolic disorder that is characterize by progressive atrophy of skeletal muscle. Cathepsin K (CTSK) is a widely expressed cysteine protease that has garnered attention because of its enzymatic and non-enzymatic functions in signalling in various pathological conditions. Here, we examined whether CTSK participates in cancer-induced skeletal muscle loss and dysfunction, focusing on protein metabolic imbalance., Methods: Male 9-week-old wild-type (CTSK +/+ , n = 10) and CTSK-knockout (CTSK -/- , n = 10) mice were injected subcutaneously with Lewis lung carcinoma cells (LLC; 5 × 10 5 ) or saline, respectively. The mice were then subjected to muscle mass and muscle function measurements. HE staining, immunostaining, quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting were used to explore the CTSK expression and IRS1/Akt pathway in the gastrocnemius muscle at various time points. In vitro measurements included CTSK expression, IRS1/Akt pathway-related target molecule expressions, and the diameter of C2C12 myotubes with or without LLC-conditioned medium (LCM). An IRS1 ubiquitin assay, and truncation, co-immunoprecipitation, and co-localization experiments were also performed., Results: CTSK +/+ cachectic animals exhibited loss of skeletal muscle mass (muscle weight loss of 15%, n = 10, P < 0.01), muscle dysfunction (grip strength loss > 15%, n = 10, P < 0.01), and fibre area (average area reduction > 30%, n = 5, P < 0.01). Compared with that of non-cachectic CTSK +/+ mice, the skeletal muscle of cachectic CTSK +/+ mice exhibited greater degradation of insulin receptor substrate 1 (IRS1, P < 0.01). In this setting, cachectic muscles exhibited decreases in the phosphorylation levels of protein kinase B (Akt 308 , P < 0.01; Akt 473 , P < 0.05) and anabolic-related proteins (the mammalian target of rapamycin, P < 0.01) and increased levels of catabolism-related proteins (muscle RING-finger protein-1, P < 0.01; MAFbx1, P < 0.01) in CTSK +/+ mice (n = 3). Although there was no difference in LLC tumour growth (n = 10, P = 0.44), CTSK deletion mitigated the IRS1 degradation, loss of the skeletal muscle mass (n = 10, P < 0.01), and dysfunction (n = 10, P < 0.01). In vitro, CTSK silencing prevented the IRS1 ubiquitination and loss of the myotube myosin heavy chain content (P < 0.01) induced by LCM, and these changes were accelerated by CTSK overexpression even without LCM. Immunoprecipitation showed that CTSK selectively acted on IRS1 in the region of amino acids 268 to 574. The results of co-transfection of IRS1-N-FLAG or IRS1-C-FLAG with CTSK suggested that CTSK selectively cleaves IRS1 and causes ubiquitination-related degradation of IRS1., Conclusions: These results demonstrate that CTSK plays a novel role in IRS1 ubiquitination in LLC-induced muscle wasting, and suggest that CTSK could be an effective therapeutic target for cancer-related cachexia., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Pannexin (PANX) family proteins form large-pore channels that mediate purinergic signaling. We analyzed the cryo-EM structures of human PANX1 in lipid nanodiscs to elucidate the gating mechanism and its regulation by the amino terminus in phospholipids. The wild-type channel has an amino-terminal funnel in the pore, but in the presence of the inhibitor probenecid, a cytoplasmically oriented amino terminus and phospholipids obstruct the pore. Functional analysis using whole-cell patch-clamp and oocyte voltage clamp showed that PANX1 lacking the amino terminus did not open and had a dominant negative effect on channel activity, thus confirming that the amino-terminal domain played an essential role in channel opening. These observations suggest that dynamic conformational changes in the amino terminus of human PANX1 are associated with lipid movement in and out of the pore. Moreover, the data provide insight into the gating mechanism of PANX1 and, more broadly, other large-pore channels.

The aging brain undergoes structural changes even in very healthy individuals. Quantifying these changes could help disentangle pathologic changes from those associated with the normal human aging process. Using longitudinal magnetic resonance imaging (MRI) data from 227 carefully selected healthy human cohort with age ranging from 50 to 80 years old at baseline scan, we quantified age-related volumetric changes in the brain of healthy human older adults. Longitudinally, the rates of tissue loss in total gray matter (GM) and white matter (WM) were 2497.5 and 2579.8 mm 3 per year, respectively. Across the whole brain, the rates of GM decline varied with regions in the frontal and parietal lobes having faster rates of decline, whereas some regions in the occipital and temporal lobes appeared relatively preserved. In contrast, cross-sectional changes were mainly observed in the temporal-occipital regions. Similar longitudinal atrophic changes were also observed in subcortical regions including thalamus, hippocampus, putamen, and caudate, whereas the pallidum showed an increasing volume with age. Overall, regions maturing late in development (frontal, parietal) are more vulnerable to longitudinal decline, whereas those that fully mature in the early stage (temporal, occipital) are mainly affected by cross-sectional changes in healthy older cohort. This may suggest that, for a successful healthy aging, the former needs to be maximally developed at an earlier age to compensate for the longitudinal decline later in life and the latter to remain relatively preserved even in old age, consistent with both concepts of reserve and brain maintenance., (Copyright © 2022 Bagarinao et al.)

This prospective, cross-sectional, cohort observational study was conducted to evaluate the associations between sedentary behavior and arteriosclerosis-related vascular issues in community-dwelling frail older adults. We included 116 Japanese community-dwelling older adults (92 females and 24 males) who availed daycare at two long-term care insurance facilities in the cities of Yokkaichi and Handa between 2017 and 2019. An unpaired t -test and the chi-square test were used for intergroup comparisons. Logistic regression analysis was conducted with cardio-ankle vascular index as the dependent variable, sedentary behavior as the explanatory variable, and the other evaluated factors as covariates. Long-time sedentary behavior (based on the median value for all participants) was associated with high cardio-ankle vascular index after adjusting for age, sex, body mass index, ankle-brachial index, and walking MET-minutes in 1 week (odds ratio 3.086, 95% confidence interval 1.275-7.467, p =0.012). After adjusting for other variables (care needs certificate, skeletal muscle mass index, body fat percentage, grip strength, 4-m walking duration, etc), there was a significant association between long-time sedentary behavior and high cardio-ankle vascular index values (odds ratio 4.977, 95% confidence interval 1.497-16.554, p =0.009). The results study confirmed an association between long-time sedentary behavior in frail older adults and the degree of arterial stiffness assessed by the cardio-ankle vascular index. Interventions in older adults that focus on daily sedentary time to prevent the onset and exacerbation of geriatric syndromes secondary to the progression of arteriosclerosis warrant further investigation., Competing Interests: The authors report no conflicts of interest.

Aim: This study performed anthropometric measurements for Werner syndrome (WS) using bioelectrical impedance analysis and compared them with the Japanese reference data., Methods: The analytical sample included nine participants with WS (four men, five women, 49.6 ± 9.3 years, SD). The height-corrected appendicular skeletal muscle mass index (SMI), upper- and lower-limb muscle mass index (USMI/LSMI) of the patients with WS were compared with the Japanese reference data (40-79 years). The body mass index, SMI, height-corrected fat mass index (FMI) and fat-free mass index (FFMI) were compared with the reference data of Japanese older adults (65-94 years). The SMIs of WS were also compared with the diagnostic criteria for sarcopenia., Results: The SMI and USMI/LSMI of all participants with WS were lower than the Japanese reference data corresponding to gender and age, and the rate of decrease was more pronounced for USMI than for LSMI. The body mass index, SMI and FFMI for all the WS cases were lower than those for the older Japanese, while the FMI was higher in men with WS but lower in women than the reference data of the older Japanese. The SMI was below the cut-off value for the diagnosis of sarcopenia in all patients with WS., Conclusion: The SMI for WS is comparable with that for sarcopenia and significantly lower than that for healthy individuals of the same age and older adults. The USMI was significantly lower than LSMI in patients with WS, and FMI was higher in male patients with WS and lower in women than in healthy older people. Geriatr Gerontol Int 2022; 22: 75-80., (© 2021 Japan Geriatrics Society.)

Older adults have physical and metabolic characteristics, and there are many differences in nutritional outcomes from middle-aged adults. In addition, there are many factors that cause malnutrition peculiar to the older adults, which are not seen in middle-aged adults, and it is easy for them to lose weight and become malnourished. Therefore, nutritional management needs to take into account the age of each subject. Uniform nutritional management can even cause poor health outcomes. The concept of frailty, especially phenotype frailty, and sarcopenia, which have been advocated with the aging of the population and the extension of life expectancy around the world, is very important in considering the extension of healthy life expectancy. In other words, in the super-aged society, frailty and sarcopenia have been emphasized as factors of functional decline, physical dysfunction, and the need for long-term care in addition to the well-known diseases such as cardiovascular disease, malignant tumors, and infectious disease. In fact, these two conditions are strongly associated with the increased risk of new disease development, falls, fractures, disability, hospitalization and death in the older adults. These two conditions are primarily associated with malnutrition and decreased dietary protein intake, and may recover to robustness again with appropriate interventions such as nutritional therapy. Therefore, undernutrition measures are more important for prevention of frailty and sarcopenia than measures for obesity against metabolic syndrome in the older adults, especially in the late-stage older people.

Background: Older adults, especially those with cognitive decline, often have poor gait performance, which results in poor clinical outcomes due to falls or decreased daily physical activity. The effects of various exercises on gait performance have been studied, whereas the short-term and long-term effects of different exercise modalities remain unknown., Objective: To compare the short- and long-term effects of aerobic training (AT), resistance training (RT), and combined training (CT) on the gait performance of community-dwelling older adults with subjective cognitive decline (SCD)., Design: A four-arm, randomized controlled trial., Setting and Subjects: 388 community-dwelling older adults with SCD (mean age, 72.3 years)., Methods: Participants attended an exercise or education class twice a week for 26 weeks. 10 gait performance parameters were examined at baseline, post-intervention (Week 26), and after 26 weeks of follow-up (Week 52) using an electronic walkway system., Results: The mean adherence of exercise sessions was 82.5 to 85.9%. All exercise intervention induced an improvement in gait speed, stride time, cadence, stride length, and double-support time at Week 26 (p < .05), without significant intergroup differences among exercise interventions. However, only RT showed a significant effect on some spatiotemporal gait parameters at Week 52. The analyses for the gait variability parameters showed mild effects of all exercise interventions., Conclusion: All of the exercise programs examined had a positive short-term effect on spatiotemporal gait parameters of older adults with SCD, despite no effect on gait variability parameters. RT are most recommended when long-lasting effects are the primary aim., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We recently demonstrated that proliferin-1 (PLF-1) functions as an apoptotic cell-derived growth factor and plays an important role in vascular pathobiology. We therefore investigated its role in muscle regeneration in response to cardiotoxin injury., Methods and Results: To determine the effects of PLF-1 on muscle regeneration, we used a CTX-induced skeletal muscle injury model in 9-week-old male mice that were administered with the recombinant PLF-1 (rPLF-1) or neutralizing PLF-1 antibody. The injured muscles exhibited increased levels of PLF-1 gene expression in a time-dependent manner. On day 14 after injury, rPLF-1 supplementation ameliorated CTX-induced alterations in muscle fiber size, interstitial fibrosis, muscle regeneration capacity, and muscle performance. On day 3 postinjury, rPLF-1 increased the levels of proteins or genes for p-Akt, p-mTOR, p-GSK3 α / β , p-Erk1/2, p-p38MAPK, interleukin-10, Pax7, MyoD, and Cyclin B1, and it increased the numbers of CD34 + /integrin- α 7 + muscle stem cells and proliferating cells in the muscles and/or bone marrow of CTX mice. An enzyme-linked immunosorbent assay revealed that rPLF-1 suppressed the levels of plasma tumor necrosis factor- α and interleukin-1 β in CTX mice. PLF-1 blocking accelerated CTX-related muscle damage and dysfunction. In C2C12 myoblasts, rPLF-1 increased the levels of proteins for p-Akt, p-mTOR, p-GSK3 α / β , p-Erk1/2, and p-p38MAPK as well as cellular functions; and these effects were diminished by the depletion of PLF-1 or silencing of its mannose-6-phosphate receptor., Conclusions: These findings demonstrated that PLF-1 can improve skeletal muscle repair in response to injury, possibly via the modulation of inflammation and proliferation and regeneration, suggesting a novel therapeutic strategy for the management of skeletal muscle diseases., Competing Interests: The authors declare that they have no conflicts of interest to disclose with respect to this manuscript., (Copyright © 2021 Hiroki Goto et al.)

Aim: Cerebral small vessel disease and lower urinary tract symptoms are common in older people. However, the association between white matter hyperintensity (WMH) and overactive bladder (OAB) is not fully understood. We aimed to identify the relationship between WMH and OAB., Methods: We carried out neuropsychological testing and head magnetic resonance imaging (T2-weighted and fluid-attenuated inversion recovery) of 72 outpatients at a memory clinic and evaluated their Overactive Bladder Symptom Score. WMH was assessed using the Fazekas scale, and WMH volumes were determined using Software for Neuro-Image Processing in Experimental Research. OAB was diagnosed based on a urinary urgency score (the third question of the Overactive Bladder Symptom Score) of two or higher and a total Overactive Bladder Symptom Score of three or higher. Multivariate logistic analysis was carried out, with the presence/absence of overactive bladder as the outcome variable, and age, sex, body mass index and diabetes mellitus as covariates., Results: Of the 72 participants, 17 (24%) were diagnosed with OAB. WMH assessed by the visual rating scale was not associated with OAB. However, participants with OAB showed significantly higher WMH volume than those without OAB. Regionally, participants with OAB showed high WMH volume in the frontal, occipital and parietal lobes. Multiple logistic regression analysis showed that WMH was significantly associated with OAB (OR 1.82, 95% CI 1.11-2.98), after adjustment for clinically important confounders., Conclusions: Cerebral WMH volume is associated with OAB, independent of age, sex, body mass index and diabetes mellitus. Geriatr Gerontol Int 2021; 21: 996-1002., (© 2021 Japan Geriatrics Society.)

Background: Social frailty is associated with poor health outcomes; however, its effects on healthy aging indicators have not been adequately investigated. This study assessed the longitudinal association between social frailty and the intrinsic capacity of community-dwelling older adults., Methods: A total of 663 participants (56.7% women) aged ≥60 years from in Nagoya, Japan, were included in the study. The first measurement occurred in 2014, and annual follow-ups occurred until 2017. Social frailty was determined based on four items: financial difficulty, household status, social activity, and regular contact with others. A deficit score of 0 represented social robustness, 1 represented social prefrailty, and ≥ 2 represented social frailty. Intrinsic capacity was evaluated by the locomotion, cognition, psychological function, vitality, and sensory function domains. The longitudinal association was analyzed using generalized estimating equations., Results: The prevalence of social prefrailty and social frailty at baseline was 31.2 and 6.3%, respectively. The social prefrailty group (β = - 0.132, P < 0.001) and social frailty group (β = - 0.258, P < 0.001) were associated with a greater reduction in the composite intrinsic capacity scores than the social robustness group, especially in the cognition, psychological function, and vitality domains. Men with social prefrailty/social frailty demonstrated a greater decrease in the psychological function domain score (- 0.512 vs. - 0.278) than women. Additionally, the cognition domain score only decreased in men in the social prefrailty/social frailty group (β = - 0.122, P = 0.016)., Conclusions: Social frailty was associated with intrinsic capacity and its subdomains longitudinally. Men with social frailty were more vulnerable than women to a decline in their psychological function and cognition domains. Therefore, the advanced management of social frailty is necessary to facilitate healthy aging., (© 2021. The Author(s).)

The thalamus is critical for the brain's integrative hub functions; however, the localization and characterization of the different thalamic hubs remain unclear. Using a voxel-level network measure called functional connectivity overlap ratio (FCOR), we examined the thalamus' association with large-scale resting-state networks (RSNs) to elucidate its connector hub roles. Connections to the core-neurocognitive networks were localized in the anterior and medial parts, such as the anteroventral and mediodorsal nuclei areas. Regions functionally connected to the sensorimotor network were distinctively located around the lateral pulvinar nucleus but to a limited extent. Prominent connector hubs include the anteroventral, ventral lateral, and mediodorsal nuclei with functional connections to multiple RSNs. These findings suggest that the thalamus, with extensive connections to most of the RSNs, is well placed as a critical integrative functional hub and could play an important role for functional integration facilitating brain functions associated with primary processing and higher cognition., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Purpose: The WHO has proposed a novel model of healthy aging called intrinsic capacity (IC). However, the association between dietary patterns and IC is unclear. We aimed to investigate the prospective associations between dietary patterns and IC trajectories over a 3-year period in community-dwelling Japanese adults aged ≥ 60 years., Methods: A prospective cohort study which contained nutritional status, mental status, and physical function was used. A validated 34-item food frequency questionnaire was used to determine dietary intake and to derive five dietary patterns ("fruits and vegetables", "sugar and fat", "salt and pickles", "noodle and alcohol", and "protein-rich") using principal component analysis. The composite IC score was calculated as the mean of the locomotion Z-score, cognition Z-score, psychological Z-score, vitality Z-score, and sensory regression score. A generalized estimating equation was applied for longitudinal analysis., Results: A total of 666 enrollees were included in the analysis. The mean baseline IC was 0.07 ± 0.47. The "fruits and vegetables" dietary pattern was positively associated with composite IC score changes after adjusting for confounders (Q4 vs. Q1: mean difference [0.069], P = 0.019). Similarly, a positive correlation was observed for the "protein-rich" dietary pattern with the composite IC score changes (Q4 vs. Q1: mean difference [0.092], Q3 vs. Q1: mean difference [0.101], Q2 vs. Q1: mean difference [0.083]; all P < 0.01). However, adherence to the "sugar and fat" dietary pattern was negatively associated with composite IC score changes (Q4 vs. Q1: mean difference [- 0.072], P = 0.026). Furthermore, the percentage of animal protein to total protein intake showed a significant incremental trend in the "protein-rich" dietary pattern (P for trend < 0.001)., Conclusion: The "fruits and vegetables" and "protein-rich" (animal-based protein in particular) dietary patterns were positively associated with IC changes, whereas the "sugar and fat" dietary pattern was negatively associated with IC changes. Identification and promotion of healthy dietary patterns in older adults may inform future health policies and research., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Aim: We examined the effects of active learning education on arterial stiffness and physical activity of community-dwelling older adults with low health literacy., Methods: This study is a secondary analysis of randomized controlled trial of 60 participants aged 65 and older with low health literacy. The intervention group (n=30) participated in a weekly 90-minute active learning program session for 24 weeks, which addressed health promotion in older age. The control group (n=30) attended a 90-minute health education class in a didactic manner. The outcomes were measured at baseline and in week 24. The degree of arterial stiffness was assessed based on the cardio-ankle vascular index (CAVI) using the VS-1500 device (Fukuda Denshi Co., Ltd., Tokyo, Japan). The shortened version of the self-reported International Physical Activity Questionnaire was used to assess the amount of total physical activity determined by the metabolic equivalent hours per week. We used analysis by intention-to-treat, with multiple imputation for missing data., Results: Seven participants (11.7%) dropped out prior to the post-intervention assessment. The multiple imputation analysis revealed that the intervention group showed significant improvement in CAVI [between-groups difference (95% confidence interval)=-0.78 (-1.25 to -0.31), Cohen's d=0.82] and physical activity [32.5 (0.3 to 64.7), Cohen's d=0.57] as compared with the control group. The sensitivity analysis for the complete cases showed similar results., Conclusion: Active learning health education may be effective in improving arterial stiffness and physical activity in older adults with low health literacy.

Objectives: Exposure to chronic psychosocial stress is a risk factor for atherosclerotic cardiovascular diseases. Given that the 3-hydroxy-3-methylglutaryl-coenzyme reductase inhibitor statins prevent atherogenesis, we evaluated whether pitavastatin prevents chronic stress- and high fat diet-induced vascular senescence and atherogenesis in apolipoprotein E -deficient ( ApoE -/- ) mice, with a special focus on glucagon-like peptide-1 (GLP-1)/adiponectin (APN) axis., Methods and Results: 6-week-old ApoE -/- mice loaded a high-fat diet were randomly assigned into non-stress ( n = 12) and stress ( n = 13) groups for 12 weeks. Non-stress control mice were left undisturbed. Chronic stress accelerated high fat diet-induce arterial senescence and atherosclerotic plaque growth. The chronic stress lowered the levels of circulating GLP-1 as well as adipose and plasma APN. As compared with the stress alone mice, the pitavastatin-treated mice had reduced macrophage infiltration, elastin fragments, and increased plaque collagen volume, and lowered levels of osteopontin, toll-like receptor-2/-4, macrophage chemoattractant protein-1, C-X-C chemokine receptor-4, p47 phox , p47 phox , gp91 phox , cathepsins S, p16, and p21, mRNAs and/or proteins. Pitavastatin increased plasma GLP-1 and APN levels and suppressed matrix metalloproteinase-2/-9 gene expressions and activities in the aortas. Finally, the protective effect of pitavastatin was abrogated by APN blocking., Conclusion: These findings suggested that the pitavastatin-mediated pleiotropic vasculoprotective effects are likely attributable, at least in part, to the elevation of GLP-1 and APN levels and the inhibition of diet-induced plaque inflammation, oxidative stress, and proteolysis in ApoE -/- mice received chronic stress conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lei, Cui, Yang, Piao, Inoue, Wu, Li, Kuzuya and Cheng.)

Background: Hospital-associated complications are associated with adverse outcomes after discharge, and a method to help predict the occurrence of these complications needs to be established. Sarcopenia is thought to be one of the factors associated with hospital-associated complication, but sarcopenia assessment in hospitalized patients is often difficult. Focus has recently been placed on morphological and qualitative evaluation of muscle by ultrasound as an index of sarcopenia. Therefore, in this study, we sought to clarify the association of hospital-associated complication with muscle thickness or echo intensity measured by ultrasound and with commonly used sarcopenia-related parameters., Methods: This is a prospective observational cohort study with 156 hospitalized older patients recruited over a year. Bilateral thigh muscle thickness of rectus femoris and vastus intermedius, echo intensity and corrected echo intensity of rectus femoris were measured by ultrasound. Also measured were the sarcopenia-related parameters of handgrip strength, skeletal muscle index, and maximum calf circumference. Hospital-associated complication was defined as the occurrence of any of the following complications: delirium, functional decline, incontinence, falls, pressure injuries, and nosocomial infections., Results: Of 156 patients enrolled at admission, hospital-associated complication was observed in 70 (54.3%). With-hospital-associated complication group had a higher prevalence of emergency admission and a higher corrected echo intensity than without-hospital-associated complication group. Multivariate logistic regression analysis showed that only higher corrected echo intensity was associated with hospital-associated complication (odds ratio 1.036; 95% confidence interval, 1.001-1.072), while handgrip strength, bilateral thigh muscle thickness, skeletal muscle index, and maximum calf circumference were not., Conclusions: Corrected echo intensity might be a useful parameter to help predict hospital-associated complication in acute hospitalized older patients and might contribute to establishing a strategy to prevent hospital-associated complication., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Neighborhood physical characteristics have been consistently associated with the health of older adults. This article investigates links between frailty and perceptions of the neighborhood environment. Using a cross-sectional analysis of 370 community-dwelling older adults from Nagoya, Japan, neighborhood perceptions were assessed using the Neighborhood Environmental Walkability Scale (NEWS) in addition to frailty, using a frailty index. Frailty was associated with the NEWS composite index, land use mix diversity, land use mix access, street connectivity, walking infrastructure, aesthetics, and crime safety, after adjustment for covariates. Older adults with increasing frailty have poorer perceptions of their neighborhoods, which could lead to further constriction of the life-space, less social and physical engagement, and worsening of frailty status.

Purpose: Social factors are often overlooked when considering physical frailty. The purpose of this study was to determine whether social isolation is associated with new onset of physical frailty among healthy Japanese older adults., Methods: This was a 1-year prospective cohort study conducted in Japan from August 2014 to August 2015. The participants were 229 Japanese older people (106 men, 123 women, mean age = 69.3 ± 4.2 years) who did not have prefrailty or frailty at baseline and who were current students or graduates of a community college for older people in Japan. Social isolation was assessed using the Lubben Social Network Scale-6 in terms of overall social isolation, family-related social isolation, and friendship-related social isolation. Frailty was categorized using the Fried frailty criteria. The association between new onset of physical frailty and baseline characteristics, including social isolation, was investigated., Results: At 1-year follow-up, 180 (78.6%) of the participants remained robust, while 49 (21.4%) were identified as prefrail; no participants were identified as frail. Prefrailty was only associated with friendship-related social isolation (odds ratio: 4.58, 95% confidence interval 2.11-9.92, P < 0.001) at baseline. No significant associations were observed for any other baseline characteristics, including overall social isolation, family-related social isolation, comorbidities, body composition, and physical function., Conclusion: Older adults with friendship-related social isolation are four times more likely to develop prefrailty from robust during the 1-year follow-up. The results suggest that friendship-related social isolation increases the risk of healthy older adults transitioning from robust to prefrail.

Objectives: Physical activity is associated with improvement in overall health and well-being, but robust evidence with comprehensive assessment of general health is lacking. This study aimed to clarify the effects of physical activity on intrinsic capacity among community-dwelling older adults with subjective memory concerns., Design: A single-blind randomized controlled trial compared aerobic training (AT), resistance training (RT), and combined training (AT+RT) programs for improving general health evaluated by intrinsic capacity., Setting: Toyota, Japan., Participants: Residents (65-85 years old) who screened positive for subjective memory concerns using the Kihon checklist were invited for eligibility assessment. In total, 415 community-dwelling older adults were enrolled and randomized into the AT, RT, AT+RT, and control groups., Methods: Participants in the intervention groups underwent a group training program and self-paced home training for 26 weeks. The control group received lectures about health promotion. Intrinsic capacity (IC), constructed based on locomotion, cognition, psychological function, and vitality domains, was used to assess general health at baseline, week 26, and week 52. Between-group differences were exhibited with Z-score change in individual domain and combination of all domains., Results: At baseline, mean age of all participants (47% women) was 72.3 ± 4.6 years, with a mean composited IC Z-score of -0.2 ± 0.5. Overall, AT and RT improved composite IC Z-scores by 0.17 (95% confidence interval [CI] 0.03-0.30) and 0.17 (95% CI 0.05-0.28) at week 26, respectively, but the beneficial effects waned at week 52. No significant differences in composite IC Z-scores were found in the AT+RT group at weeks 26 and 52., Conclusions and Implications: Twenty-six-week AT with self-paced home training and RT with self-paced home training improve IC among community-dwelling older adults with subjective memory concerns, but the benefits waned subsequently. It will be required to develop optimal interventions that have a continuous beneficial effect on IC among community-dwelling older adults., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: This study addressed a two-part question. First, is cognitive decline associated with fear of falling (FoF)? Second, if this association is observed, is there also an association between FoF and physical activity (PA) independent of cognitive decline?, Methods: Participants in the study were community-dwelling Japanese residents between 65 and 85 years of age (N = 458, mean age = 72.4 ± 4.6, male = 53.7%). Step counts were recorded, as was objectively measured PA, divided into (1) low-intensity PA and (2) moderate- and vigorous-intensity PA. Three groups were determined based on FoF: low, moderate, and high. Neuropsychological tests were also conducted., Results: Participants with high FoF had slower processing speed. low-intensity PA was associated with only high FoF, but after controlling for processing speed, the significance of this association was attenuated. Shorter time of moderate- and vigorous-intensity PA was associated with high FoF, even in the full model controlling for other factors. All FoF levels were associated with lower step counts., Conclusion: older community-dwelling adults with high FoF were found to have had declined cognitive speed/ Second, both moderate and high FoF were associated with moderate- and vigorous-intensity PA and step counts in older community-dwelling adults, with the high FoF group performing shorter time of moderate- and vigorous-intensity PA and fewer steps.

Aim: Sarcopenia is defined as a condition that combines decreased skeletal muscle mass with weakness or decreased physical function. It is well known that in older adults, the presence of sarcopenia is a risk of frailty, falls and physical dysfunction. Patients with Werner syndrome are characterized by visceral fat accumulation and thin limbs, but the prevalence of sarcopenia in patients with Werner syndrome has not been investigated., Methods: A literature search was conducted using Werner syndrome and skeletal muscle as keywords. We also analyzed data from our 7 Werner syndrome patients., Results: A literature search on the relationship between Werner syndrome and skeletal muscle yielded only one article reported from Japan. According to this paper, a decrease in skeletal muscle mass (appendicular skeletal muscle index) was observed in all 9 Werner syndromes investigated. On the other hand, in our 7 Werner syndrome patients, their appendicular skeletal muscle indexes were below the standard value except for one male patient who had continued resistance exercise., Conclusion: The decrease in skeletal muscle mass frequently occurs in patients with Werner syndrome. However, resistance exercise may prevent the appearance of sarcopenia and requires early intervention in patients with Werner syndrome. Geriatr Gerontol Int 2021; 21: 139-141., (© 2020 Japan Geriatrics Society.)

Aim: To clarify the diagnostic value of the calcification in the Achilles tendon for Werner syndrome., Methods: Calcification of the Achilles tendon in the plain radiograph was investigated in 92 patients with Werner syndrome provided from the nationwide secondary survey in 2010. And the same investigation was performed for 2151 feet in 1853 patients without Werner syndrome, who underwent foot and ankle surgeries at the department of orthopaedic surgery in Nara Medical University from 2004 to 2015., Result and Conclusion: Achilles tendon calcification was observed in 70 (76.1%) out of 92 patients with Werner syndrome, whereas that was observed only in 19 feet (0.88%) without Werner syndrome, accompanied by 1 to 4 calcified masses with a maximum diameter ranging from 9.7mm to 63.2mm. The frequency of Achilles tendon calcification in patients with Werner syndrome is far higher than that of patients without Werner syndrome. Achilles tendon calcification could be included in the diagnostic criteria for Werner syndrome. Geriatr Gerontol Int 2021; 21: 163-165., (© 2020 Japan Geriatrics Society.)

Aims: To evaluate the characteristics of diabetes associated with Werner syndrome., Methods: A literature search was done with search term "Werner syndrome" and "Diabetes"., Results and Conclusions: Prevalence of diabetes is extremely high in Werner syndrome. Diabetes associated with Werner syndrome is classified as "accompanied with other diseases and conditions and the one occurring mainly in association with other genetic syndromes." This type of diabetes is marked by accumulated visceral fat and high insulin resistance, despite low body mass index. Thiazolidine derivatives and metformin are effective for glycemic control. New antidiabetic drugs, such as dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists, could be potentially beneficial for patients with Werner syndrome. Furthermore, the establishment of diet therapy as well as exercise therapy is warranted. Geriatr Gerontol Int 2021; 21: 142-145., (© 2020 Japan Geriatrics Society.)

Skin ulcers in Werner's syndrome often arise from hyperkeratotic lesions and trauma to pressure points such as the plantar region, and are more difficult to treat than wound healing in healthy individuals. Multiple factors contribute to the intractable skin ulcers in Werner's syndrome, including skin thinning, sclerosis, fatty tissue loss, impaired blood flow, calcification, and excessive pressure due to osteoarticular deformity. Treatment includes topical application of a keratolytic agent for keratosis around the ulcer. Treatment of ulcers is the same as for normal ulcers, and if the ulcer is associated with infection and necrotic tissue, surgical debridement with a scalpel or scissors should be performed as much as possible after washing with saline or mildly warm water or with an antibacterial agent. Topical medications that promote softening and debridement of the necrotic tissue are used with careful control of moisture in the wound. Topical agents that promote granulation should be used in wounds where necrotic tissue has been removed without infection. Dressings to maintain a moist environment in the wound may also be useful. If the wound does not improve with conservative treatment, surgical treatment should be considered. Geriatr Gerontol Int 2021; 21: 160-162., (© 2020 Japan Geriatrics Society.)

For the purpose of examining the characteristics of dyslipidemia and fatty liver in patients with Werner syndrome in Japan in recent years, we searched all case reports of Japanese Werner syndrome reported on Medical Online and PubMed since 1996, and collected and examined the data and clinical features described in these reports. In addition, as there are few descriptions of treatment methods in these reports from Medical Online and PubMed, we analyzed 12 cases for which detailed data on treatment methods are available at Chiba University. Geriatr Gerontol Int 2021; 21: 133-138., (© 2020 Japan Geriatrics Society.)

Aim: To provide guidelines on the diagnosis, treatment, and prevention of skin ulcers in Werner syndrome., Methods: This article was based on literature from 1996, when WRN was identified as a gene responsible for Werner syndrome, and we evaluated several authentic clinical cases of genetically diagnosed patients. There were 63 patients with Werner syndrome in the Japanese reports retrieved from Medical Online between January 1996 and December 2017. There were 56 patients with Werner syndrome in English reports written by Japanese authors and retrieved from PubMed during the same period., Results: Records on skin ulcers were found in 27 (43%) out of 63 patients and 22 (40%) out of 56 patients from the Japanese and English reports, respectively. The reported ulcers were often located at the distal one-third of the lower legs. There were 8 patients with callosities in the foot in the Japanese reports and 9 patients in the English reports. A skin ulcer in Werner syndrome is generally intractable. Weight-bearing ulcers or callosity should be critically assessed in surgical procedures because they have effects on patient pain and gait. By adopting a recently advanced technique to facilitate wound healing, the cases of ulcers that were difficult to treat and those requiring major operations can be closed with minimally invasive surgery., Conclusions: Skin ulcers in Werner syndrome are refractory, and they lead to reduced quality of life of patients. A callosity in Werner syndrome is an important therapeutic target for the prevention of ulcers. Geriatr Gerontol Int 2021; 21: 153-159., (© 2020 Japan Geriatrics Society.)

Background: Mild hyponatremia (serum sodium 130-135 mEq/L) is a common electrolyte disorder in the elderly. However, its association with both sarcopenia and cognitive function remains to be clarified. Therefore, here we investigated the association of mild hyponatremia with skeletal muscle mass, physical function, and cognitive function in the elderly., Methods: We enrolled 75 participants with mild hyponatremia and 2907 with normonatremia (serum sodium, 136-145 mEq/L) aged ≥70 years who visited the Memory Disorder Outpatient Center of Japan's National Center for Geriatrics and Gerontology. Skeletal muscle mass index (SMI), grip strength (GS), walking speed (WS), one-leg standing (OLS) test times, and neuropsychological test scores were determined., Results: One-way analysis of covariance showed that elderly participants with mild hyponatremia had lower SMI (7.1 ± 0.2, 7.2 ± 0.2 kg/m 2 , p = 0.04), weaker GS (19.1 ± 1.9 vs 21.4 ± 1.8 kg, p = 0.01), slower WS (0.9 ± 0.1 vs 1.1 ± 0.1 m/s, p = 0.001), and higher GDS- 15 score (6.4 ± 0.9 vs 5.2 ± 0.9, p = 0.002) than those with normonatremia. Multiple logistic regression analysis indicated that mild hyponatremia was independently associated with sarcopenia (odds ratio [OR]: 2.2, p = 0.02), slower WS (OR: 5.3, p = 0.04) and shorter OLS time (OR: 2.5, p = 0.02) as well as with severe depressive mood (OR: 2.6 p = 0.006) but not with SMI (OR: 1.6, p = 0.2) or GS (OR: 1.9, p = 0.09)., Conclusions: Our results suggest that elderly people with even mild hyponatremia had physical function impairment and depressive mood.

Background: Physical exercise is suggested to be effective for preventing cognitive decline in older adults, but the relative efficacy of different types of exercise have yet to be clarified., Objective: This single-blinded randomized controlled trial was designed to investigate the differential effects of aerobic exercise training (AT), resistance exercise training (RT), and combined exercise training (CT) on cognition in older adults with subjective memory complaints (SMC)., Methods: Community-dwelling older adults with SMC (n = 415; mean age = 72.3 years old) were randomly assigned to one of the four groups: AT, RT, CT, or control group. The study consisted of two phases: a 26-week intervention and a 26-week follow-up. The participants were evaluated at baseline, 26 weeks (postintervention), and 52 weeks (follow-up). The primary outcome of this study was memory function, which was assessed using the Logical Memory II subtest of the Wechsler Memory Scale-Revised (WMS-R) score. The secondary outcomes included global cognitive function, verbal fluency, working memory, processing speed, and executive functions., Results: Intention-to-treat analysis by a mixed-effect model repeated measure showed that the AT group had significantly improved performance on the WMS-R Logical Memory II test (2.74 [1.82-3.66] points) than the control group (1.36 [0.44-2.28] points) at the postintervention assessment (p = 0.037). The effect was more pronounced in those without amnesia than those with amnesia. No significant improvement was observed in the RT and CT groups., Conclusion: This study suggests that AT intervention can improve delayed memory in community-dwelling older adults, particularly in individuals without objective memory decline.

Objectives: Previous studies have reported a relationship between low protein intake and cognitive decline and have suggested that this association may be related to specific amino acid intake. However, the effects of amino acid intake on the maintenance of cognitive function have yet to be clarified. We examined the longitudinal association between dietary amino acid intake and cognitive function in community-dwelling older adults., Design: Longitudinal epidemiological study., Setting: Community-based setting., Participants: This study comprised 427 study participants aged 60-82 years with no cognitive decline, defined as a Mini-Mental State Examination (MMSE) score of >27 at baseline, who also participated in a follow-up. The average and standard deviation of the follow-up period was 8.2 ± 0.3 years., Measurements: Dietary intake was assessed using three-day dietary records at baseline. Participants were classified into quartiles (Q1-Q4) based on the intake of 19 amino acids for males and females. Next, we classified participants into Q1 and Q2-Q4 groups. Cognitive function was assessed using the MMSE both at baseline and at follow-up. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between the Q1 group and cognitive decline (MMSE ≤27), using the Q2-Q4 group as a reference group. Covariates were age, sex, body mass index, years of education, severity of depressive symptoms, history of lifestyle diseases (hypertension, dyslipidemia, diabetes mellitus, stroke, and ischemic heart disease), energy intake (kcal/d), protein intake (g/d), and MMSE score at baseline., Results: Cognitive decline was present in 133 (31.1%) participants. After adjustment for covariates, including total protein intake, the ORs (95% CIs) for cognitive decline were 2.40 (1.21-4.75) for lysine, 2.05 (1.02-4.09) for phenylalanine, 2.18 (1.09-4.34) for threonine, and 2.10 (1.06-4.15) for alanine., Conclusion: The results suggest that lysine, phenylalanine, threonine, and alanine intake is important for the maintenance of cognitive function in older people, independent of total protein intake., Competing Interests: Michihiro Takada, Akira Imaizumi, and Masako Tsukamoto-Yasui are employees of Ajinomoto Co., Inc., Kaori Kinoshita, Rei Otsuka, and Hidenori Arai received grants from Ajinomoto Co., Inc. Kaori Kinoshita, Rei Otsuka, Michihiro Takada, Masako Tsukamoto-Yasui, Akira Imaizumi, and Hidenori Arai have applied for patents for “Food evaluation methods for cognitive function”.

Background: Polypharmacy, usually defined as the use of 5 or more drugs, is associated with reduced quality of life, adverse events, and frailty. Slow gait speed is a component of physical frailty, and some studies have suggested an association between polypharmacy and slow gait speed., Objective: We aimed to determine the effects of polypharmacy on the gait difference according to stages of cognitive decline in a cross-sectional study of memory clinic patients., Methods: Participants were 431 outpatients aged 65 year or older who were cognitively normal (CN) or had mild cognitive impairment (MCI) or dementia due to Alzheimer's disease. Participants were divided into a polypharmacy group and a non-polypharmacy group in each group. Multiple regression analysis and logistic analysis were used for data analysis., Results: There were 182 patients in the polypharmacy group and 249 patients in the non-polypharmacy group. Multiple regression analysis revealed that gait speed had significant negative associations with number of medications and polypharmacy status in the CN group (β: -0.026 [-0.041 to -0.0018] and -0.128 [-0.022 to -0.0033], respectively) and MCI group (-0.018 [-0.028 to -0.0009] and -0.100 [-0.166 to -0.0034]). Logistic regression analysis also showed that number of medications was associated with slow gait status (< 1 m/s) in the CN group (OR: 1.336 [1.115 to 1.601]) and MCI group (1.128 [1.022 to 1.244])., Conclusion: CN and MCI patients with polypharmacy have slower gait speed. Attention should be paid to decreased gait speed in older adults with polypharmacy even when their cognitive function is relatively preserved.

Background: Few studies have investigated associations between types of clock drawing test (CDT) errors and cognitive impairment., Objective: To explore associations of qualitative errors in the CDT with comprehensive neurocognitive assessment scores and clinical diagnosis., Methods: Outpatients at a memory clinic were enrolled. Frequencies of errors determined by Cahn's method were explored according to cognitive status (cognitively normal [CN] (n = 279), mild cognitive impairment [MCI] (n = 321), and Alzheimer's disease [AD]) (n = 575). Neuropsychological assessment scores were compared between participants with and without errors., Results: Stimulus-bound response (SB) was relatively rare (6.8%) in the CN group but was markedly more common in the MCI (23.4%) and AD (33.2%) groups. Conceptual deficit (CD) was found in more than 20%of CN individuals, as well as about 50%of AD patients. Planning deficit (PD) frequencies were relatively similar among the groups. SB in both of CN and MCI individuals, and CD in both of CN and MCI individuals were associated with lower scores in several neuropsychological assessments. Meanwhile, PD was not associated with lower assessment scores in any of CN, MCI, or AD individuals., Conclusion: The frequencies of SB and CD increased from CN, MCI, to AD but showed somewhat different patterns. Both SB and CD were associated with lower cognition in all three cognitive stages.

Background/objectives: The Japan-multimodal intervention trial for prevention of dementia (J-MINT) is intended to verify the effectiveness of multi-domain interventions and to clarify the mechanism of cognitive improvement and deterioration by carrying out assessment of dementia-related biomarkers, omics analysis and brain imaging analysis among older adults at high risk of dementia. Moreover, the J-MINT trial collaborates with partnering private enterprises in the implementation of relevant interventional measures. This manuscript describes the study protocol., Design/setting: Eighteen-month, multi-centered, randomized controlled trial., Participants: We plan to recruit 500 older adults aged 65-85 years with mild cognitive impairment. Subjects will be centrally randomized into intervention and control groups at a 1:1 allocation ratio using the dynamic allocation method with all subjects stratified by age, sex, and cognition., Intervention: The multi-domain intervention program includes: (1) management of vascular risk factors; (2) group-based physical exercise and self-monitoring of physical activity; (3) nutritional counseling; and (4) cognitive training. Health-related information will be provided to the control group every two months., Measurements: The primary and secondary outcomes will be assessed at baseline, 6-, 12-, and 18-month follow-up. The primary outcome is the change from baseline to 18 months in a global composite score combining several neuropsychological domains. Secondary outcomes include: cognitive change in each neuropsychological test, incident dementia, changes in blood and dementia-related biomarkers, changes in geriatric assessment including activities of daily living, frailty status and neuroimaging, and number of medications taken., Conclusions: This trial that enlist the support of private enterprises will lead to the creation of new services for dementia prevention as well as to verify the effectiveness of multi-domain interventions for dementia prevention., Competing Interests: The authors have no conflict of interest to declare.

Good nutritional status is crucial for maintaining growth and health in all stages of life. However, the relationship between nutritional status and health and the effect on various health-related outcomes differ, depending on the life stage. Many adverse outcomes in older adults, directly linked to different nutritional status, are not present in middle-aged adults, and their ideal nutritional status may differ. This article will review the optimal nutritional status, mainly evaluated by anthropometric measurements such as body mass index, for older adults from various perspectives. Overall, in older adults low body mass index is at higher risk of health problems such as mortality and difficulties in physical functioning compared with middle-aged adults, reducing the risk of health problems for overweight and (abdominal) obesity. Overweight may be more beneficial than lower level of normal weight in older-old and vulnerable older people. While, with or without obesity, skeletal muscle loss or weakness as well as unintentional weight loss induces health problems in older adults. The impact of metabolic syndrome on the prognosis of older adults is clearly reduced compared with middle-aged adults, requiring a shift in medical attention in older adults from metabolic syndrome to frailty. There are still many unclear points regarding the optimal nutritional status of older people, and further research is needed to support healthy longevity. Geriatr Gerontol Int 2021; 21: 5-13., (© 2020 Japan Geriatrics Society.)

Background & Aims: The association between dietary patterns and frailty is less investigated in Asia. We aimed to investigate the prospective associations between dietary patterns and frailty index (FI) in community-dwelling Japanese older adults aged 60 years or older., Methods: A 3-year cohort collected the data on sociodemographic information, lifestyle behaviors, comorbidities, medication history, depression status, nutrition, and physical function from 2014 to 2017. Five dietary patterns including "Mediterranean-style," "sugar and fat," "salt and pickles," "noodle and alcohol," and "protein-rich" dietary patterns were identified using principal component analysis from 20 food groups obtained using a validated food frequency questionnaire. A 54-item FI was constructed on the basis of a deficit accumulation model. This project aimed to investigate the longitudinal association between dietary pattern and frailty trajectories with annual measurements over a 3-year period using a generalized estimating equation., Result: After excluding 108 participants with incomplete data at baseline, 666 participants (56.5% female, 69.4 ± 4.4 years) were included for longitudinal analysis. Our results demonstrated that adherence score to "sugar and fat" dietary pattern" (Q4 vs. Q1: mean difference [0.017], 95% CI [0.006 to 0.029]) and "salt and pickles" dietary pattern (Q3 vs. Q1: mean difference [0.010], 95% CI [0.001 to 0.020]; Q4 vs. Q1: mean difference [0.014], 95% CI [0.003 to 0.025]) were positively associated with change in FI. Adherence score to a "protein-rich" dietary pattern was negatively associated with change in FI (Q4 vs. Q1: mean difference [-0.013], 95% CI [-0.025 to -0.002])., Conclusions: "Salt and pickles" dietary pattern and "sugar and fat" dietary pattern were positively associated with frailty. In contrast, "protein-rich" dietary pattern was negatively associated with frailty., Competing Interests: Conflict of Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objectives: Nutritional support effectively prevents and treats sarcopenia; however, the influence of overall dietary patterns on sarcopenia parameters is less investigated. This study aimed to determine the association between adherence to Mediterranean-style diet (MD), Dietary Approaches to Stop Hypertension (DASH), Japanese Food Guide Spinning Top (JFG-ST), and modified JFG-ST (mJFG-ST) and muscle mass, muscle strength, and physical performance in community-dwelling Japanese elderly., Design and Settings: This prospective cohort study recruited individuals aged over 60 years from a community college in Nagoya, Japan., Participants and Measurements: A total of 666 participants were followed up annually from 2014 to 2017. Demographic data, anthropometric measurements, and sarcopenia parameters including walking speed (WS), hand grip strength in the dominant hand (HGS), and skeletal mass index (SMI) were recorded. Self-recall dietary intake was assessed using a validated food frequency questionnaire comprising 29 food groups. Adherence to MD, DASH, JFG-ST, and mJFG-ST was determined by tertiles., Results: At baseline, the mean age of all participants (56.5% women) was 69.4±4.4 years. WS, HGS, and SMI were 1.4±0.2 (m/s), 28.9±8.1 (kg), and 6.7±1.0 (kg/m2), respectively. In longitudinal analysis, participants with higher JFG-ST adherence scores were more likely to have higher SMI (Q3 vs. Q1: mean difference, 0.048; p=0.04) after adjustment, and its benefits were more evident in men (Q2 vs. Q1: mean difference, 0.098; p=0.047; Q3 vs. Q1: mean difference, 0.091; p=0.017) than in women. WS and HGS were not associated with any type of dietary pattern., Conclusions: Adherence to JFG-ST was positively associated with SMI in Japanese community-dwelling elderly adults aged over 60 years, specifically in men. The country-specific dietary recommendations are required to be developed for sarcopenia prevention., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Homocysteine is a common risk factor for cognitive impairment and sarcopenia. However, very few studies have shown an association between sarcopenia and serum homocysteine levels after adjustment for cognitive function., Objective: The purpose of this study was to investigate the relationship between homocysteine and sarcopenia in memory clinic patients., Methods: This cross-sectional study investigated outpatients in a memory clinic. We enrolled 1,774 participants (≥65 years old) with measured skeletal muscle mass index (SMI), hand grip strength (HGS), and homocysteine. All participants had undergone cognitive assessments and were diagnosed with dementia, mild cognitive impairment, or normal cognition. Patient characteristics were compared according to sarcopenia presence, SMI level, or HGS. Multivariate logistic regression analysis was performed to determine the association of homocysteine with sarcopenia, low SMI, or low HGS. Next, linear regression analysis was performed using HGS as a continuous variable., Results: Logistic regression analysis showed that low HGS was significantly associated with homocysteine levels (p = 0.002), but sarcopenia and low SMI were not. In linear regression analysis, HGS was negatively associated with homocysteine levels after adjustment for Mini-Mental State Examination score (β= -2.790, p < 0.001) or clinical diagnosis of dementia (β= -3.145, p < 0.001). These results were similar for men and women., Conclusion: Our results showed a negative association between homocysteine and HGS after adjustment for cognitive function. Our findings strengthen the assumed association between homocysteine and HGS. Further research is needed to determine whether lower homocysteine levels lead to prevent muscle weakness.

In Japan, which has become a super-aged society, medical care for the elderly is more important than ever before. Geriatric education for medical students and young doctors is essential to ensure the best medical care possible for the elderly. In this paper, the Working Group for Education of the Japan Geriatrics Society collected and analyzed data and information on undergraduate education in the fields of geriatrics and gerontology at medical schools in various countries through the Internet, comparing the findings with those in Japan. Of the countries surveyed, 62% had undergraduate education in geriatrics and gerontology as mandatory subjects in medical school. Countries with advanced welfare programs, such as the United Kingdom, Germany, Austria, Denmark, Finland, Sweden, the Netherlands, Spain, Canada and New Zealand, performed substantial undergraduate education in geriatrics and gerontology. A lack of available staff and time for education was cited as a hurdle in many countries. The importance of education in geriatrics and gerontology is being emphasized in many countries, but few programs are satisfactory at present. The "struggle" to improve undergraduate education in geriatrics and gerontology therefore continues. We should endeavor to improve education in the fields of geriatrics and gerontology by working hand in hand with geriatricians and gerontologists around the world.

Patients with Werner syndrome present with diverse signs of aging that begin in adolescence. A Japanese nationwide survey was conducted to establish a registry that could clarify the disease profile of patients with Werner syndrome. The questionnaires were sent to 7888 doctors. The survey identified 116 patients diagnosed with Werner syndrome based on the diagnosis criteria. Forty patients were enrolled in the registry. Data on clinical symptoms, treatment information, and laboratory examination from patients who provided informed consent were collected. The data at enrollment were analyzed. The patients' average age at enrollment was 50.1±7.5 years. The mean onset age was 26.1±9.5 years, but the mean age at diagnosis was 42.5±8.6 years. Average height and weight of the study patients were lower than those of Japanese individuals. Almost all patients experienced hair change and cataracts. More than 60% of patients presented with glycolipid abnormalities. Overall, 15% of patients had a history of foot amputation. Approximately 30% of the patients' parents had a consanguineous marriage. The average grip strength, walking speed, and skeletal muscle mass index met the diagnostic criteria for sarcopenia. The registry revealed that there are opportunities for early diagnosis and intervention; therefore, sensitization about the disease is needed.