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In this randomized, double-blind, placebo-controlled study, we investigated the effects of collagen peptides (CP) containing high concentrations of prolyl-hydroxyproline and hydroxyprolyl-glycine on the advanced glycation end products (AGEs) levels in the skin and subcutaneous blood vessel walls. Thirty-one individuals aged 47–87 years were randomly assigned to receive either 5 g/day fish-derived CP or a placebo for 12 weeks. Body and blood compositions and AGEs levels were measured at the beginning and end of the study. No adverse events were observed, and both groups’ blood and body compositions did not change significantly. However, the CP group had significantly lower AGEs levels and a slightly lower insulin resistance index (HOMA-R) than the placebo group. In addition, the % changes in AGEs and HOMA-R levels were positively and strongly correlated in both groups. These findings suggest that fish-derived CP may be effective in reducing AGEs levels and improving insulin resistance.

We examined the effect of 5.0 g/day of collagen peptide (CP) or collagen peptide fermented with Aspergillus sojae (FCP) on skin pigmentation in healthy participants.In this randomized, double-blind, placebo-controlled study, 44 men and women aged 25-63 years were placed into three groups by stratified random allocation and treated with CP, FCP, or placebo (PL) at 5.0 g/day for 3 months. Their skin condition was measured monthly from baseline to 3 months of intake.No adverse events were identified in any group. The CP group showed a significant reduction in pigmented patches and redness after 1 and 3 months of intake, respectively. In the FCP group, pigmented macules were significantly reduced after 1 month, and pigmented patches after 2 months. Both the all-ages analysis and the hierarchical analysis below 55 years old yielded similar results.Intake of 5.0 g/day of FCP for 3 months is safe. CP and FCP intake is useful for suppressing pigmentation. In addition, CP intake may be useful for reducing redness. These results suggest a new beneficial effect on the skin of CP supplementation.UMIN clinical trials registry system, UMIN000040736.

Casein hydrolysate has been shown to improve arterial stiffness as estimated by brachial-ankle pulse wave velocity (baPWV) in untreated hypertensive patients. Facial pigmentation is associated with atherosclerosis, both of which are supposed to be modulated by tissue accumulation of advanced glycation end products (AGEs). However, effects of casein hydrolysate on facial pigmentation and AGEs remain largely unknown. This randomized double-blind placebo-controlled trial evaluated whether and how casein hydrolysate improves facial pigmentation in 80 nonhypertensive Japanese patients. Study participants were randomly assigned to receive either active tablets containing casein hydrolysate or placebo for 48 weeks. Facial pigmentation area, baPWV, and skin accumulation levels of AGEs were evaluated by Robo Skin Analyzer RSA50S II, volume-plethysmographic apparatus, and AGE Reader, respectively, at baseline and at the end of the intervention. Treatment with casein hydrolysate, but not placebo significantly reduced triglycerides and facial pigmentation area. There were significant differences of changes in triglycerides, facial pigmentation area, skin accumulation levels of AGEs, and baPWV between the two groups. Furthermore, changes in triglycerides and skin accumulation levels of AGEs were positively and independently associated with those in facial pigmentation area, whereas changes in baPWV were not. This study suggests that casein hydrolysate reduces facial pigmentation area in nonhypertensive participants partly by decreasing skin accumulation levels of AGEs. Clinical-Trials.gov ID: UMIN000027675.

Background: Tight junction (TJ) disruption and dysfunction are involved in the progression of arteriosclerosis. miR-501-3p regulates endothelial TJ protein-1, resulting in TJ disruption. Because exosomal microRNAs can travel to distant tissues and influence cell behavior, patients with elevated miR-501-3p may experience accelerated vascular disease progression secondary to miR-501-3p-induced reductions in TJ. This study investigated whether plasma exosome miR-501-3p levels are associated with vascular stiffness, an indicator for arteriosclerotic changes. Methods and Results: Fifty-one subjects (mean [±SD] age 70±8 years, 37% male) enrolled in a medical checkup program were recruited to the study. Brachial-ankle arterial pulse wave velocity (baPWV) and plasma exosome miR-501-3p expression were measured. Patients were divided into 2 groups depending on whether their miR-501-3p ∆Ct values were above (“High”; n=24) or below (“Low”; n=27) the cut-off levels determined by receiver operating characteristic (ROC) curve analysis. Median (interquartile range) baPWV levels were significantly higher in the miR-501-3p High than Low group (1,664 [1,496–1,859] vs. 1,450 [1,353–1,686] cm/s, respectively; P

Summary Background Sarcopenia increases mortality risk in older adults. Loss of skeletal muscle mass is a cardinal feature of sarcopenia. The creatinine-to-cystatin C ratio (CCR) has been suggested as a marker of muscle mass. The present study investigated the usefulness of CCR in discriminating the risk of low muscle mass and weak muscle strength in an elderly population. Methods The present cross-sectional study included 1,329 apparently healthy community residents aged 60 years or older. The cross-sectional area (CSA) of muscle in the mid-thigh was measured using computed tomography. Clinical data recorded at routine medical check-ups were obtained from each participant's medical record. Results Mean muscle CSA was 109 ± 24 cm2. CCR by quartiles according to sex was strongly associated with muscle CSA (Q1: 104 ± 22, Q2: 108 ± 24, Q3: 110 ± 23, and Q4: 114 ± 25 cm2, F = 10.38, P Conclusion CCR was a simple marker of low muscle mass and weak muscle strength in older community-dwelling adults.

Sarcopenia is the age-associated atrophy of muscles, and advanced glycation end-products (AGEs) accumulate in patients with age-associated diseases. We aimed to investigate the relationship between AGE accumulation in the skin and sarcopenia in middle-aged and older Japanese people.We enrolled 240 participants in this cross-sectional study. The participants consisted of 120 men (mean age 68.8 ± 10.1 years) and 120 women (mean age 67.4 ± 9.0 years). The level of dermal AGE accumulation in the forearms was measured using skin autofluorescence (SAF) and many parameters associated with sarcopenia, including grip strength and thigh muscle cross-sectional area (CSA), were evaluated during medical check-ups at the Ehime University Hospital.Grip strength and thigh muscle CSA were significantly higher in men than women, but mean SAF did not significantly differ between them. There were significant correlations of age, height, C-reactive protein, glycated hemoglobin, grip strength, and thigh muscle CSA with SAF in men, but only age in women. Multivariate analysis showed that SAF was significantly independently associated with low grip strength in men (β =-0.211, p =0.046). The men were then allocated to four groups according to their grip strength and thigh muscle CSA, and SAF was significantly higher in the lowgrip strength/low-thigh muscle CSA group than in the high-grip strength/high-thigh muscle CSA group (low/low group 2.25 ± 0.37 and high/high group 1.93 ± 0.36, p =0.001).SAF is associated with sarcopenia-related measures, especially grip strength, in middle-aged and older Japanese men, but not women.

Background We assessed cases of incidental unruptured intracranial aneurysm (UIA) discovered on screening magnetic resonance angiography to identify hemodynamic and atherosclerotic risk factors. Methods and Results The data of 1376 healthy older subjects (age range, 31–91 years) without cerebro‐ or cardiovascular diseases who underwent brain magnetic resonance angiography as part of a medical checkup program at a health screening center were examined retrospectively. We looked for an increase in classical risk factors for UIAs (age, sex, hypertension, and smoking) and laboratory data related to lifestyle diseases among subjects with UIAs. Brachial‐ankle pulse wave velocity, central systolic blood pressure, radial augmentation index, and carotid flow pulsatility index were also compared between those with and without UIAs. We found UIAs in 79 (5.7%) of the subjects. Mean age was 67.1±9.0 years, and 55 (70%) were women. Of the 79 aneurysms, 75 (95%) were in the anterior circulation, with a mean diameter of 3.1 mm (range, 2.0–8.0 mm). Subjects with UIAs were significantly older and had more severe hypertension. The carotid flow pulsatility index was significantly lower in subjects with UIAs and negatively and independently correlated with UIAs. Tertile analysis stratified by carotid flow pulsatility index revealed that subjects with lower indices had higher levels of low‐density lipoprotein cholesterol. Conclusions The presence of UIAs correlated with lower carotid flow pulsatility index and elevated low‐density lipoprotein cholesterol in the data from a population of healthy older volunteers. A reduced carotid flow pulsatility index may affect low‐density lipoprotein cholesterol elevation by some molecular pathways and influence the development of cerebral aneurysms. This may guide aneurysm screening indications for institutions where magnetic resonance angiography is not routine.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

Sarcopenia is a risk factor for poor outcomes in older adults. Identification of plasma markers may facilitate screening of sarcopenia. We previously reported that creatinine-to-cystatin C ratio is a simple marker of muscle mass. To further assess the clinical relevance of the creatinine-to-cystatin C ratio, we investigated its association with myosteatosis and physical performance.Observational study.Cross-sectional analysis of the dataset obtained from a Japanese population consisting of 1468 older (≥60 years of age) community residents.The mean attenuation values of the skeletal muscle calculated from computed tomography images of the midthigh were used as an index of myosteatosis, while the cross-sectional area of the muscle was used as a proxy for muscle mass. Physical performance was assessed by 1-leg standing time.Creatinine-to-cystatin C ratio was positively associated with the cross-sectional area of muscle fiber-rich muscles, while it showed an inverse association with fat-rich muscle areas, resulting in the positive association between creatinine-to-cystatin C ratio and the mean attenuation value of the skeletal muscle [creatinine-to-cystatin C ratio quartiles (Q), Q1: 47.4 ± 4.8, Q2: 48.9 ± 4.4, Q3: 49.8 ± 4.1, Q4: 50.9 ± 3.7, P .001]. The results of the linear regression analysis adjusted for major covariates (including muscle cross-sectional area) identified creatinine-to-cystatin C ratio as an independent determinant of the mean attenuation value (Q1: reference, Q2: β = 0.07, P = .019, Q3: β = 0.11, P .001, Q4: β = 0.16, P .001). Low creatinine-to-cystatin C ratio was independently associated with 1-leg standing time, although the association was attenuated substantially by adjusting for skeletal muscle cross-sectional area and mean attenuation value.Creatinine-to-cystatin C ratio was associated with myosteatosis in older adults, independent of the muscle mass. Creatinine-to-cystatin C ratio may serve as a convenient marker of sarcopenia.

Objectives Sarcopenia is defined as a combination of low skeletal muscle mass index (SMI), weak muscle strength, and reduced physical function. Recently, many studies have reported that the creatinine/cystatin C ratio (Cr/CysC) is useful for evaluating muscle mass. We designed a cross-sectional study with separate model development and validation groups to develop a prediction equation to estimate bioimpedance analysis (BIA)-measured SMI with Cr/CysC. Design The current study was a retrospective cross-sectional study. Setting and Participants The model development group included 908 subjects (288 men and 620 women) from the Frail Elderly in the Sasayama-Tamba Area (FESTA) study, and the validation group included 263 subjects (112 men and 151 women) from participants in the medical checkup program at the Anti-Aging Center in Ehime Prefecture. Measures Multivariate regression analysis indicated that age, hemoglobin (Hb), body weight (BW), and Cr/CysC were independently associated with SMI in both men and women. The SMI prediction equation was developed as follows: Men: 4.17 − 0.012 × Age + 1.24 × ( Cr / CysC ) − 0.0513 × Hb + 0.0598 × BW Women: 3.55 − 0.00765 × Age + 0.852 × ( Cr / CysC ) − 0.0627 × Hb + 0.0614 × BW Results The SMI prediction equation was applied to the validation group and strong correlations were observed between the BIA-measured and predicted SMI (pSMI) in men and women. According to the receiver operator characteristic (ROC) analysis, the areas under the curve were 0.93 (specificity 89.0%, sensitivity 87.2%) among men and 0.88 (specificity 83.6%, sensitivity 79.6%) among women for using pSMI to identify low SMI in the model development group. The pSMI also indicated high accuracy in ROC analysis for low SMI in the validation group. The Bland-Altman plot regression showed good agreement between BIA-measured and pSMI. Conclusions and Implications Our new prediction equation to estimate SMI is easy to calculate in daily clinical practice and would be useful for diagnosing sarcopenia.

The elderly experience numerous physiological alterations. In the brain, aging causes degeneration or loss of distinct populations of neurons, resulting in declining cognitive function, locomotor capability, etc. The pathogenic factors of such neurodegeneration are oxidative stress, mitochondrial dysfunction, inflammation, reduced energy homeostatis, decreased levels of neurotrophic factor, etc. On the other hand, numerous studies have investigated various biologically active substances in fruit and vegetables. We focused on the peel of citrus fruit to search for neuroprotective components and found that: 1) 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) and auraptene (AUR) in the peel of Kawachi Bankan (Citrus kawachiensis) exert neuroprotective effects; 2) both HMF and AUR can pass through the blood-brain barrier, suggesting that they act directly in the brain; 3) the content of AUR in the peel of K. Bankan was exceptionally high, and consequently the oral administration of the dried peel powder of K. Bankan exerts neuroprotective effects; and 4) intake of K. Bankan juice, which was enriched in AUR by adding peel paste to the raw juice, contributed to the prevention of cognitive dysfunction in aged healthy volunteers. This review summarizes our studies in terms of the isolation/characterization of HMF and AUR in K. Bankan peel, analysis of their actions in the brain, mechanisms of their actions, and trials to develop food that retains their functions.

We describe a 61-year-old woman with bilateral parkinsonism caused by unilateral infarction limited to the territory of the lenticulostriate arteries. Although dopamine transporter imaging with single-photon emission computed tomography (DaTSPECT) demonstrated reduced putaminal tracer binding concordant with the size and location of the vascular lesion, the specific binding ratio was within the normal range. Five months after onset, the patient was free from parkinsonism without the use of any antiparkinsonian agents. When patients show bilateral parkinsonism, it is important to consider infarction of the lenticulostriate arteries. Additionally, DaTSPECT might be useful for predicting the prognosis of parkinsonism caused by infarction., Highlights • We present a case with bilateral parkinsonism caused by unilateral striatum infarcts. • DaTSPECT showed right putamen hypoactivity. • However, specific binding ratio was within the normal range. • Her symptoms fully recovered without antiparkinsonian agents. • DaTSPECT may be useful for us to predict a patient's prognosis.

Background Glomus tumors are soft tissue neoplasms comprised of glomus cells, vasculature, and smooth muscle cells, which occur commonly in a single subungual area of the digits, and their main clinical features include severe paroxysmal pain, localized tenderness, and cold hypersensitivity. Case presentation A 47-year-old Japanese man had suffered from chronic progressive paroxysmal shooting pain in his right leg since childhood. He avoided putting weight on his right foot whenever he walked. The frequency of paroxysmal pain and the number of tender points both gradually increased with age, and his right leg gradually atrophied. Magnetic resonance imaging of the lower extremity demonstrated multiple gadolinium-enhanced nodules that corresponded with his tender points. Excisional biopsy relieved his pain and provided a histopathological diagnosis of glomus tumors. Conclusion This case suggests that small glomus tumors located in deep tissue may cause disuse atrophy because of their long delay before diagnosis. Clinicians should consider the potential for glomus tumors when patients exhibit unilateral lower limb muscular atrophy with pain.

We assembled an ancestrally diverse collection of genome-wide association studies of type 2 diabetes (T2D) in 180,834 cases and 1,159,055 controls (48.9% non-European descent). We identified 277 loci at genome-wide significance (p-8), including 237 attaining a more stringent trans-ancestry threshold (p-9), which were delineated to 338 distinct association signals. Trans-ancestry meta-regression offered substantial enhancements to fine-mapping, with 58.6% of associations more precisely localised due to population diversity, and 54.4% of signals resolved to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying foundations for functional investigations. Trans-ancestry genetic risk scores enhanced transferability across diverse populations, providing a step towards more effective clinical translation to improve global health.

The clinical implications of alcohol consumption have been extensively examined; however, its effects on brain structures in apparently healthy community-dwellers remain unclear. Therefore, we investigated the relationship between alcohol consumption and brain gray matter volume (GMV) in community-dwelling Japanese men using voxel-based morphometry (VBM). We recruited cognitively intact Japanese men, aged 40-79 years, from a population-based cohort in Shiga, Japan. Brain magnetic resonance imaging was performed, on average, 2 years after demographic and medical information was obtained in 2010-2014. A multivariable linear regression analysis of 639 men was conducted to elucidate the relationship between the amount of alcohol consumed and GMV. VBM statistics were analyzed by threshold-free cluster enhancement with a family-wise error rate of, Research members：Minoru Horie, Yoshihisa Nakagawa, Takashi Yamamoto, Yasutaka Nakano, Emiko Ogawa, Hiroshi Maegawa, Katsutaro Morino, Itsuko Miyazawa, Yoshiyuki Watanabe, Kazuhiko Nozaki, Ikuo Tooyama, Akihiko Shiino, Akira Andoh, Teruhiko Tsuru, Hisakazu Ogita, Naomi Miyamatsu, Yasuyuki Nakamura, Aya Kadota, Keiko Kondo, Sayuki Torii, Takashi Kadowaki, Sayaka Kadowaki, Sentaro Suzuki, Takahiro Ito, Ayako Kunimura, Hiroyoshi Segawa, Akira Fujiyoshi, Aya Higashiyama, Tomonori Okamura, Koichiro Azuma, Tatsuya Sawamura, Michiya Igase, Yasuharu Tabara, Akira Sekikawa, Emma J M Barinas-Mitchell, Daniel Edmundowicz, Takayoshi Ohkubo, Atsushi Hozawa, Yoshitaka Murakam, Nagako Okuda, Hisatomi Arima, Atsushi Satoh, Yoshikuni Kita, Takashi Hisamatsu, Masahiko Yanagita, Robert D Abbott, Seiko Ohno, Naoyuki Takashima, Naoko Miyagawa, Maryam Zaid, Yoshino Saito

Glycaemic traits are used to diagnose and monitor type 2 diabetes, and cardiometabolic health. To date, most genetic studies of glycaemic traits have focused on individuals of European ancestry. Here, we aggregated genome-wide association studies in up to 281,416 individuals without diabetes (30% non-European ancestry) with fasting glucose, 2h-glucose post-challenge, glycated haemoglobin, and fasting insulin data. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P-8), 80% with no significant evidence of between-ancestry heterogeneity. Analyses restricted to European ancestry individuals with equivalent sample size would have led to 24 fewer new loci. Compared to single-ancestry, equivalent sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase understanding of diabetes pathophysiology by use of trans-ancestry studies for improved power and resolution.

Casein hydrolysate improves arterial stiffness, as estimated by brachial ankle pulse wave velocity (baPWV), in untreated hypertensive subjects. Facial pigmentation is a useful biomarker for arterial stiffness. This trial evaluated whether casein hydrolysate improves facial pigmentation in association with changes in arterial stiffness. A randomized, double-blind, placebo-controlled trial was conducted in 80 non-hypertensive Japanese participants randomly assigned to receive either active tablets containing casein hydrolysate or placebo for 48 weeks. Facial pigmentation and baPWV were measured at baseline and at the end of the intervention. Other biochemical atherosclerosis-related parameters were also measured, including advanced glycation end products (AGEs). Changes in facial pigmentation showed a significant difference between the groups. Change in baPWV was significantly better in the active than in the placebo group. In contrast, no significant association was seen between changes in facial pigmentation and those in baPWV. Among other atherosclerosis-related factors, changes in advanced glycation products (AGEs) were significantly decreased in the active compared to the placebo group. Further, changes in facial pigmentation were positively correlated with those in AGEs. Changes in AGEs were independently associated with changes in facial pigmentation. Casein hydrolysate improves facial pigmentation in non-hypertensive participants. Casein hydrolysate may have beneficial effects on glycation stress.

To clarify whether serum creatinine to cystatin C ratio (CCR), a marker of muscle mass and muscle function may be used as a simple marker of bone property. A cross-sectional analysis. A general population-based observation study. Participants: 1,606 middle-aged to elderly (≥50 years, mean age: 66.9 ± 7.5 years old) men (n = 642) and post-menopausal women (n = 964). Speed of sound (SOS) at the calcaneal bone was used as a surrogate marker of bone mineral density. The cross-sectional area of the muscle at the mid-thigh was measured using computed tomography. There was significant linear correlation between the quartiles of CCR and SOS (Q1: 1,495 ± 25, Q2: 1,499 ± 24, Q3: 1,507 ± 26, Q4: 1,511 ± 25 m/sec; P < 0.001) even in a sex-separated analysis. This association was independent of major covariates (Q1: β = −0.126, P < 0.001; Q2: β = −0.096, P = 0.001; Q3: β = −0.022; P = 0.412, Q4: reference) and the mid-thigh muscle mass, while creatinine alone or eGFR did not show clear association with SOS. The CCR may be used as a simple marker of bone property independently of muscle mass in a general population with preserved renal function.

Our previous report indicated that sarcopenia is associated with arterial stiffness and cardiovascular death. The renin-angiotensin system (RAS) plays an important role in cardiovascular disease and its activation may be correlated with sarcopenia according to basic research. However, few clinical studies have assessed the correlation between skeletal muscle loss and RAS component concentrations in healthy subjects. The purpose of this study was to investigate the relationships between the excretion of angiotensinogen (AGT) and aldosterone (Ald) in 24-h urine samples and clinical and sarcopenic indices. A total of 344 people participated in a voluntary medical check-up program, "Anti-Aging Doc", and underwent measurement of their sarcopenia-related indices. Urine samples were collected for 24-h within 8 weeks after a medical check-up using a partition cup and a proportional sampling method. Urine AGT and Ald levels were evaluated by enzyme-linked immunosorbent assay (ELISA). After compensating for possible confounding parameters, including baPWV, the 24-h urinary excretion of AGT was independently and negatively associated with the thigh muscle cross-sectional area. On the other hand, urinary Ald excretion was not associated with sarcopenia-related indices after compensation, even though it showed a modest but significantly positive association with sarcopenic indices in single regression analysis. Urinary AGT was related to sarcopenic indices and may be involved in the pathogenesis of sarcopenia. On the other hand, urinary Ald was not related to sarcopenic indices when considering other risk factors.

Background Impairment of cerebrovascular reactivity (CVR) has been reported in patients with multiple sclerosis (MS). Chronic inflammation and endothelial dysfunction are possible mechanisms underlying this hemodynamic impairment. This study aimed to evaluate CVR and endothelial function in patients with MS and explore their relationships with disease progression using functional sonographic procedures. Methods Patients with MS and age-/sex-matched healthy controls were assessed for endothelial function, determined by flow-mediated dilation (FMD), and CVR, measured using the breath-holding index (BHI). Results Twenty-seven patients with MS and 24 healthy controls were enrolled. FMD was significantly lower in MS subjects than in control subjects (6.0 ± 0.6 vs. 8.6 ± 0.7, p = 0.006); furthermore, BHI was similarly lower in MS than in controls, but insignificant. Remarkably, FMD was significantly lower in secondary progressive MS subjects than in relapse-remitting MS subjects (3.7 ± 1.3 vs. 6.7 ± 0.7, p = 0.045). In addition, FMD was inversely correlated with the disability score as per the expanded disability status scale (R2 = 0.170, p = 0.033) and modified Rankin scale (R2 = 0.187, p = 0.027). Conclusion In patients with MS, endothelial dysfunction was more noticeable than CVR impairment, correlating with the severity and progression of MS.

Background There is a close association between frailty and cognitive impairment. However, the underlying contribution of sarcopenia to the development of cognitive impairment is unclear. We investigated the possible association between muscle mass decline and cognitive impairment in a cross-sectional study of 1518 subjects aged 55 years or above. We also evaluated arterial stiffness and white matter hyperintensities (WMHs) as possible underlying mechanisms for this association. Methods Two sarcopenic indices were measured: thigh muscle cross-sectional area (CSA; calculated by computed tomography) and skeletal muscle mass (bioelectric impedance). Muscle mass decline was defined as either the bottom 10% or 20% of participants for each sex. Cognitive function was assessed using the Touch Panel-type Dementia Assessment Scale, and brachial–ankle pulse wave velocity was measured as an index of arterial stiffness. Results Both sarcopenic indices were modestly but significantly associated with brachial–ankle pulse wave velocity in male and female subjects. The presence of WMHs was significantly associated with low thigh muscle CSA in men and with low skeletal muscle mass in women. The Touch Panel-type Dementia Assessment Scale score was modestly but significantly and positively associated with thigh muscle CSA in men and skeletal muscle mass in women. Muscle mass decline in the bottom 10% of participants on both sarcopenic indices was significantly and independently related to cognitive impairment in women. Conclusions Lower sarcopenic indices are significantly related to lower cognitive scores. Arterial stiffness and WMHs could account, at least in part, for this association.

AIM It is well known that consumption of isoflavones reduces the risk of cardiovascular disease. However, the effectiveness of isoflavones in preventing dementia is controversial. A number of intervention studies have produced conflicting results. One possible reason is that the ability to produce equol, a metabolite of a soy isoflavone, differs greatly in individuals. In addition to existing data, we sought to confirm whether an apparent beneficial effect in cognitive function is observed after soy consumption in equol producers compared with non-producers. METHODS The present study was a cross-sectional, observational study of 152 (male/female = 61/91, mean age 69.2 ± 9.2 years) individuals. Participants were divided into two groups according to equol production status, which was determined using urine samples collected after a soy challenge test. Cognitive function was assessed using two computer-based questionnaires (touch panel-type dementia assessment scale [TDAS] and mild cognitive impairment [MCI] screen). RESULTS Overall, 60 (40%) of 152 participants were equol producers. Both TDAS and prevalence of MCI were significantly higher in the equol producer group than in the non-producer group. In univariate analyses, TDAS significantly correlated with age, serum creatinine, estimated glomerular filtration rate and low-density lipoprotein cholesterol. In multiple regression analysis using TDAS as a dependent variable, equol producer (β = 0.236, P = 0.005) was selected as an independent variable. In addition, multiple logistic regression analysis to assess the presence of MCI showed that being an equol producer was an independent risk factor for MCI (odds ratio 3.961). CONCLUSIONS Compared with equol non-producers, equol producers showed an apparent beneficial effect in cognitive function after soy intake. Geriatr Gerontol Int 2017; 17: 2103-2108.

This study investigated the effects of collagen hydrolysates (CH) on language cognitive function and brain structure. In this open-label study, 5 g CH was administered once a day for 4 weeks to 30 healthy participants aged 49&ndash, 63 years. The primary outcome measures were the brain healthcare quotients based on gray matter volume (GM-BHQ) and fractional anisotropy (FA-BHQ). The secondary outcome measures were changes in scores between week 0 and week 4 for word list memory (WLM) and standard verbal paired associate learning (S-PA) tests as well as changes in the physical, mental, and role/social component summary scores of the Short Form-36(SF-36) quality of life instrument. CH ingestion resulted in significant improvements in FA-BHQ (p = 0.0095), a measure of brain structure, as well in scores for the WLM (p = 0.0046) and S-PA (p = 0.0007) tests, which measure cognitive function. There were moderate correlations between the change in WLM score and the change in GM-BHQ (r = 0.4448, Spearman&rsquo, s rank correlation) and between the change in S-PA score and the change in FA-BHQ (r = 0.4645). Daily ingestion of CH changed brain structure and improved language cognitive function.

SUMMARYMeta-analyses of genome-wide association studies (GWAS) have identified >240 loci associated with type 2 diabetes (T2D), however most loci have been identified in analyses of European-ancestry individuals. To examine T2D risk in East Asian individuals, we meta-analyzed GWAS data in 77,418 cases and 356,122 controls. In the main analysis, we identified 298 distinct association signals at 178 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 56 loci newly implicated in T2D predisposition. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. New associations include signals in/near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect muscle and adipose differentiation. At another locus, eQTLs at two overlapping T2D signals act through two genes, NKX6-3 and ANK1, in different tissues. Association studies in diverse populations identify additional loci and elucidate disease genes, biology, and pathways.Type 2 diabetes (T2D) is a common metabolic disease primarily caused by insufficient insulin production and/or secretion by the pancreatic β cells and insulin resistance in peripheral tissues1. Most genetic loci associated with T2D have been identified in populations of European (EUR) ancestry, including a recent meta-analysis of genome-wide association studies (GWAS) of nearly 900,000 individuals of European ancestry that identified >240 loci influencing the risk of T2D2. Differences in allele frequency between ancestries affect the power to detect associations within a population, particularly among variants rare or monomorphic in one population but more frequent in another3,4. Although smaller than studies in European populations, a recent T2D meta-analysis in almost 200,000 Japanese individuals identified 28 additional loci4. The relative contributions of different pathways to the pathophysiology of T2D may also differ between ancestry groups. For example, in East Asian (EAS) populations, T2D prevalence is greater than in European populations among people of similar body mass index (BMI) or waist circumference5. We performed the largest meta-analysis of East Asian individuals to identify new genetic associations and provide insight into T2D pathogenesis.

We investigated changes in blood pressure (BP) and metabolic adverse effects, especially elevation of uric acid (UA), after treatment with a thiazide-like diuretic (TD) in patients with essential hypertension. Furthermore, the role of genetic factors in the elevation of UA by TD was assessed by a 500 K SNP DNA microarray. The subjects included 126 hypertensive patients (57 women and 69 men, mean age 59 ± 12 years) who registered for the GEANE (Gene Evaluation for ANtihypertensive Effects) study. After one month of the nontreatment period, TD, indapamide, angiotensin II receptor antagonist valsartan, and Ca channel blocker amlodipine were administered to all patients for 3 months each in a randomized crossover manner. BP, renal function, serum UA level, and electrolytes were measured at baseline and at the end of each treatment period. Single nucleotide polymorphisms (SNPs) associated with UA elevation after treatment with indapamide were investigated by a genome-wide association study (GWAS). Indapamide significantly decreased both office and home BP levels. Treatment with indapamide also significantly reduced the estimated glomerular filtration rate and serum potassium and increased serum UA. Patients whose UA level increased more than 1 mg/dl showed significantly higher baseline office SBP and plasma glucose and showed greater decline in renal function compared with those who showed less UA increase (

Frailty, a geriatric syndrome reflecting a state of reduced physiological reserve and increased vulnerability, is an independent risk factor for cardiovascular morbidity and mortality. However, the relationship between frailty and hypertensive end-organ damage is not fully established.We performed a cross-sectional study to investigate the association between frailty and end-organ damage in 1125 apparently healthy middle-aged to elderly subjects. We performed a simple frailty (SF) score that was easily obtainable in the office, in combination with low hand grip power and short one-leg standing (OLS) time. The association between SF score and hypertensive end-organ damage and other frailty-related parameters was evaluated. Odds ratio of SF score 1 to score 0 for the presence of hypertension was 1.9 [1.4-2.5, p.0001] and that of SF score 2 was 3.3 [2.1-5.3, p.0001]. SF score was also significantly associated with brachial-ankle pulse wave velocity (baPWV) and central pulse pressure (PP2). SF score was significantly associated with higher frailty index calculated from 21 parameters, lower cognitive test score, % vital capacity, skeletal muscle mass, and thigh muscle cross-sectional area. SF score was positively associated with stage of brain white matter hyperintenisty, plasma levels of B-type natriuretic peptide, and urinary protein excretion, even after correction for confounding parameters including baPWV and PP2.These findings indicate that frailty is significantly associated with end-organ damage in elderly subjects. SF score may be a useful clinical tool to identify frail subjects and advanced end-organ damage in elderly subjects.

OBJECTIVES: Dementia, which is characterized by a progressive decline in cognitive function, is a major concern in aging societies. Although a number of treatments have been approved, an effective therapy to prevent the disorder is lacking. A supplement that improves cognitive function would benefit patients. The aim of this study was to assess whether auraptene, a citrus coumarin, has a protective effect on cognitive decline. DESIGN: A randomized, placebo-controlled, double-blind study SETTING: Outpatient medical check-up program for cognitive disorders PARTICIPANTS: 84 adult volunteers (they are cognitively normal) met inclusion and exclusion criteria to participate. INTERVENTION: 42 participants received auraptene enriched (containing 6.0 mg/day of auraptene) test juice, and another participants received placebo juice. MEASUREMENTS: 1) Mild Cognitive Impairment (MCI) Screen using the 10-word immediate recall test. 2) The Mini-Mental State Examination (MMSE). Cognitive assessment ware carried out baseline and at 24 weeks. RESULTS: Auraptene enriched test juice did not improve cognitive function after 24 weeks compared with baseline data. However, there was a significant difference in the percentage change in cognitive function between the test and placebo orange juice groups (6.3 ± 18.9 vs. −2.4 ± 14.8, P < 0.05). Multiple regression analysis demonstrated a significant independent relationship between the percentage change in the 10-word immediate recall test score and test juice consumption including baseline 10-word immediate recall test score in all subjects. CONCLUSION: This is the first study to assess the effectiveness of auraptene in the prevention of cognitive decline. Our results suggest that auraptene is a safe supplement for the prevention of cognitive decline.

Favorable effects of sauna bathing on cardiovascular disease have been demonstrated. Hot water bathing is an alternative, and could also have similar effects. Information pertaining to hot water bathing frequency and water temperature was obtained from 873 subjects. Carotid mean and max intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) were measured as indices of atherosclerosis. Central haemodynamics were evaluated using radial pulse waveform analyses. Plasma levels of B-type natriuretic peptide (BNP) were measured as an index for cardiac loading. The mean duration of a single hot bath was 12.4 ± 9.9 min. Subject bathing in hot water ≥5 times per week had significantly lower baPWV, central pulse pressure (PP), and BNP after correcting for possible confounding parameters. Stepwise regression analyses revealed that hot water temperature was negatively associated with baPWV, while bathing frequency was negatively related to central PP and BNP. A longitudinal follow-up in 164 subjects showed that hot water bathing ≥5 times per week was associated with significantly lower increase in BNP over time, while the temperature of the water tended to be related to lower increases in carotid max IMT and baPWV. Hot water bathing showed a favorable effect on atherosclerotic and central haemodynamic parameters.

We examined whether baPWV could be affected by pork collagen peptide (CP) ingestion. Seventy subjects were randomized into two groups (2.5 g/day CP and 2.5 g/day placebo). A significant reduction in baPWV was observed in the CP group compared to the placebo group. This study demonstrated that pork CP may contribute to the prevention of atherosclerosis in elderly.

Background/purpose Perceived age may be a better predictor of mortality rate than chronological age. We have demonstrated that perceived age was a significant biomarker for carotid atherosclerosis in Japanese. However, it remains to be determined which skin parameter is associated with atherosclerosis. The purpose of this study is to analyze the relationship between 10 facial skin-aging parameters and atherosclerosis in 169 middle-aged to elderly Japanese women who participated. Methods Facial photographs were taken under a shadowless lamp from three directions using a high-resolution digital camera. The digital images of each subject were analyzed using computer software and various parameters of skin aging such as pigmentation, wrinkles, and skin color were quantified. Carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) were measured as indices for atherosclerosis. Results Facial pigmentation showed a significant correlation with carotid IMT, even after correction for age (r = 0.13, P = 0.03), and with visceral fat area. Stepwise regression analysis indicated that facial pigmentation was associated with carotid IMT via visceral fat area. Conclusion Facial pigmentation may be a useful biomarker for carotid atherosclerosis in Japanese women.

We recently reported that thigh muscle sarcopenia measured by computed tomography is related to arterial stiffness, pressure wave reflection, and central pulse pressure (PP). However, it remains to be determined whether more straightforward and simple techniques such as hand grip strength and the bio-impedance method are also useful for the clinical evaluation of sarcopenia.A total of 1593 middle-aged to older patients participated in this cross-sectional study. Brachial-to-ankle pulse wave velocity (baPWV) was measured as an index of arterial stiffness. Second PP (PP2) at the second peak of radial SBP was used to estimate central PP. Radial augmentation index was calculated as PP2/PP. Thigh muscle cross-sectional area and abdominal visceral fat area were quantified by computed tomography. Patients were classified as sarcopenic if their hand grip strength or skeletal muscle mass (measured by bioelectrical impedance) was more than 1 SD lower than the mean of those in a reference group aged below 50 years, or in the lowest 20% of the studied population. Visceral obesity was defined as visceral fat area greater than 100 cm.Antidyslipidemia drug and antidiabetic drug were significantly associated with lower hand grip strength. Both sarcopenic indices were significantly and independently associated with baPWV, radial augmentation index, and PP2. Sarcopenia defined by either criterion was significantly associated with higher baPWV, radial augmentation index, and PP2. Visceral obesity was significantly associated only with baPWV.These findings indicate the clinical usefulness of noninvasive methods for assessment of sarcopenia, which is a risk factor for cardiovascular disease.

Objective:To develop a risk score that estimates 3-year and 5-year absolute risks for aneurysm growth.Methods:From 10 cohorts of patients with unruptured intracranial aneurysms and follow-up imaging, we pooled individual data on sex, population, age, hypertension, history of subarachnoid hemorrhage, and aneurysm location, size, aspect ratio, and shape but not on smoking during follow-up and family history of intracranial aneurysms in 1,507 patients with 1,909 unruptured intracranial aneurysms and used aneurysm growth as outcome. With aneurysm-based multivariable Cox regression analysis, we determined predictors for aneurysm growth, which were presented as a risk score to calculate 3-year and 5-year risks for aneurysm growth by risk factor status.Results:Aneurysm growth occurred in 257 patients (17%) and 267 aneurysms (14%) during 5,782 patient-years of follow-up. Predictors for aneurysm growth were earlier subarachnoid hemorrhage, location of the aneurysm, age >60 years, population, size of the aneurysm, and shape of the aneurysm (ELAPSS). The 3-year growth risk ranged from 42% and the 5-year growth risk from 60%, depending on the risk factor status.Conclusions:The ELAPSS score consists of 6 easily retrievable predictors and can help physicians in decision making on the need for and timing of follow-up imaging in patients with unruptured intracranial aneurysms.

Frailty is associated with cognitive impairment and can be used to identify people at high risk for dementia. We developed a simple frailty (SF) score using a combination of low hand grip strength (