One-leg standing time is a simple measure for loss of skeletal muscle mass and fat deposition in muscle: the J-SHIPP study.

BACKGROUNDS: One-leg standing time (OLST) has been frequently used physical performance measure; however, what muscular characteristics OLST represents remains uncertain. AIM: This cross-sectional study aimed to investigate the association between OLST and muscle characteristics to clarify the possibility of using OLST as a physical performance measure. METHODS: Study participants comprised 1144 older adults aged 65 years or older. Computed tomography images provided mid-thigh skeletal muscle cross-sectional area and mean attenuation value. OLST was measured for a maximum of 60 s. Static postural instability was assessed using a posturography. RESULTS: A frequency of OLST < 20 s was increased by quartiles of muscle cross-sectional area (Q1: 33.6, Q2: 12.8, Q3: 13.6, Q4: 11.9%, P < 0.001) and mean attenuation value (Q1: 32.3, Q2: 21.7, Q3: 14.3, Q4: 7.7%, P < 0.001). Results of the multinomial regression analysis indicated that muscle cross-sectional area and mean attenuation value were independently associated with an OLST of less than 20 s. The crude odds ratio of OLST less than 20 s for the lowest quartiles of both cross-sectional area and mean attenuation value was 4.19 (95% CI: 3.01 - 5.84). The cross-sectional area of muscles with greater fat deposition was inversely associated with OLST, while that with smaller fat deposition showed a positive association with OLST, indicating why mean attenuation value and cross-sectional area were independently associated with OLST. No clear relationship was observed with static postural instability. CONCLUSION: OLST was a simply measurable quantifiable physical measure representing the loss of muscle mass and quality in older adults.

Case report: Frontotemporal dementia and amyotrophic lateral sclerosis caused by a missense variant (p.Arg89Trp) in the valosin-containing protein gene.

Frontotemporal dementia and/or amyotrophic lateral sclerosis 6, also known as amyotrophic lateral sclerosis 14, is an autosomal dominant, progressive neurodegenerative disorder caused by various mutations in the valosin-containing protein gene. In this report, we examined a 51-year-old female Japanese patient with frontotemporal dementia and amyotrophic lateral sclerosis. The patient began noticing gait disturbances at the age of 45 years. Neurological examination at the age of 46 years met the Awaji criteria for clinically probable amyotrophic lateral sclerosis. At the age of 49 years, she tended to have poor mood and an aversion to activity. Her symptoms gradually worsened. She required a wheelchair for transport and had difficulty communicating with others because of poor comprehension. She then began to frequently exhibit irritability. Eventually, she was admitted to the psychiatric hospital because uncontrollable violent behavior throughout the day. Longitudinal brain magnetic resonance imaging revealed progressive brain atrophy with temporal dominance, non-progressive cerebellar atrophy, and some non-specific white matter intensities. Brain single photon emission computed tomography showed hypoperfusion in the bilateral temporal lobes and cerebellar hemispheres. Clinical exome sequencing revealed the presence of a heterozygous nonsynonymous variant (NM_007126.5, c.265C>T; p.Arg89Trp) in the valosin-containing protein gene, which was absent in the 1000 Genomes Project, the Exome Aggregation Consortium Database, and the Genome Aggregation Database, and was predicted to be "damaging" by PolyPhen-2 and "deleterious" using SIFT with a Combined Annotation Dependent Depletion score of 35. We also confirmed the absence of this variant in 505 Japanese control subjects. Therefore, we concluded that the variant in the valosin-containing protein gene was responsible for the symptoms of this patient.

Ingestion of a collagen peptide containing high concentrations of prolyl-hydroxyproline and hydroxyprolyl-glycine reduces advanced glycation end products levels in the skin and subcutaneous blood vessel walls: a randomized, double-blind, placebo-controlled study.

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 advanced glycation end products (AGEs) levels in the skin and subcutaneous blood vessel walls. A total of 31 individuals aged 47-87 years were randomly assigned to receive either 5 g/day of 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 (homeostasis model assessment ratio [HOMA-R]) than the placebo group. In addition, the percentage 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.

Bioimpedance phase angle is independently associated with myosteatosis: The Shizuoka study.

BACKGROUND & AIMS: Phase angle (PhA) calculated from the resistance and reactance measured using a bioimpedance device was suggested to represent the degree of fat deposition in muscle (myosteatosis), though no direct evidence is available. We aimed to clarify the possible association between PhA and skeletal muscle myosteatosis in community-dwelling middle-aged to older adults. METHODS: Participants consisted of 424 Japanese (aged ≥50 years). Leg PhA and skeletal muscle mass index (SMI) were obtained by bioelectrical impedance analysis. The mean attenuation values and cross-sectional area of the mid-thigh skeletal muscle were calculated from computed tomography images and considered as indexes of myosteatosis and skeletal muscle mass, respectively. RESULTS: Leg PhA was positively associated with SMI, and cross-sectional area and mean attenuation value at mid-thigh. Multiple regression analysis adjusted for possible covariates identified leg PhA (ß = 0.214) and SMI (ß = 0.260) as independent factors of mid-thigh muscle cross-sectional area (P < 0.001), while leg PhA (ß = 0.349, P < 0.001) but not SMI (P = 0.645) was associated with mean attenuation value. Similar results were observed in the analysis in the older (≥65 years) subpopulation. The combination of low SMI and low leg PhA showed stepwise association with cross-sectional area, while only individuals with low leg PhA had lower mean attenuated value. CONCLUSIONS: Leg PhA was independently associated with mean attenuated value of the mid-thigh skeletal muscle, suggesting that the assessment of PhA in combination with SMI could provide additional information for the evaluation of muscle properties.

Associations between adiponectin and leptin levels and skeletal muscle mass and myosteatosis in older adults: The Shimanami Health Promoting Program study.

AIM: Identifying plasma molecules associated with skeletal muscle properties can elucidate the pathophysiology of sarcopenia. Because adipocytokines are a promising candidate marker, the current study aimed to clarify the possible associations between adiponectin and leptin levels and mid-thigh muscle cross-sectional area and mean attenuation value, which are indices of muscle mass and fat deposition in muscle, respectively. METHODS: The current study included 1440 older Japanese adults (mean age 69.3 years). Mid-thigh skeletal muscle cross-sectional area and mean attenuation value were evaluated through computed tomography scan. A low attenuation value showed a greater fat deposition in muscle. Circulating adiponectin and leptin levels were assessed using blood specimens collected during the baseline investigation. RESULTS: Plasma leptin level was inversely correlated with muscle cross-sectional area, but not with attenuation value. The association with cross-sectional area was independent of possible confounding factors including body size (Q1: reference; Q2: ß = -0.032, P = 0.033; Q3: ß = -0.064, P < 0.001; Q4: ß = -0.111, P < 0.001). In contrast, adiponectin level was independently and inversely associated with attenuation value (Q1: reference; Q2: ß = -0.044, P = 0.122; Q3: ß = -0.080, P = 0.006; Q4: ß = -0.159, P < 0.001), but not with cross-sectional area. These associations between adipocytokine levels and muscle properties were independent of abdominal fat area and insulin resistance. CONCLUSIONS: There were adiposity- and insulin resistance-independent associations between adipocytokines levels and skeletal muscle mass and fat deposition in muscle, suggesting an involvement of adipocytokines in muscle properties. Geriatr Gerontol Int 2023; 23: 444-449.

Effect of Reducing Pigmentation by Collagen Peptide Intake: A Randomized, Double-Blind, Placebo-Controlled Study.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. TRIAL REGISTRATION: UMIN clinical trials registry system, UMIN000040736.

Dermal advanced glycation end-product accumulation is associated with sarcopenia-related measures in middle-aged and older men.

AIMS: 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. MATERIALS AND METHODS: 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. RESULTS: 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 (ß =-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). CONCLUSIONS: SAF is associated with sarcopenia-related measures, especially grip strength, in middle-aged and older Japanese men, but not women.

Estimation of Muscle Mass Using Creatinine/Cystatin C Ratio in Japanese Community-Dwelling Older People.

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.

Vascular endothelial dysfunction associated with severity in multiple sclerosis.

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.

Low Carotid Flow Pulsatility Index Correlates With the Presence of Unruptured Intracranial Aneurysms.

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.

Association of Creatinine-to-Cystatin C Ratio with Myosteatosis and Physical Performance in Older Adults: The Japan Shimanami Health Promoting Program.

OBJECTIVE: 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. DESIGN: Observational study. SETTING AND PARTICIPANTS: Cross-sectional analysis of the dataset obtained from a Japanese population consisting of 1468 older (≥60 years of age) community residents. METHODS: 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. RESULTS: 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: ß = 0.07, P = .019, Q3: ß = 0.11, P < .001, Q4: ß = 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. CONCLUSION AND IMPLICATIONS: 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.

Exosome miR-501-3p Elevation Contributes to Progression of Vascular Stiffness.

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<0.05). Multivariate logistic regression analysis showed a significant association between increased baPWV and High miR-501-3p expression (odds ratio 4.66). At follow-up visits (mean 62 months later), baPWV remained significantly higher in the miR-501-3p High than Low group (1,830 [1,624-2,056] vs. 1,620 [1,377-1,816] cm/s, respectively; P<0.05). Conclusions: High expression levels of exosome miR-501-3p contribute to arteriosclerotic changes.

Unilateral lower limb atrophy associated with glomus tumors: a case report.

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.

Isolation and Characterization of Neuroprotective Components from Citrus Peel and Their Application as Functional Food.

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.

Casein Hydrolysate Containing Milk-Derived Peptides Reduces Facial Pigmentation Partly by Decreasing Advanced Glycation End Products in the Skin: A Randomized Double-Blind Placebo-Controlled Trial.

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.

Bilateral parkinsonism in a patient with infarcts involving the unilateral basal ganglia.

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.

Creatinine-to-cystatin C ratio as a marker of skeletal muscle mass in older adults: J-SHIPP study.

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 < 0.001). This association was independent of major covariates (Q1: reference, Q2: ß = 0.06, P < 0.001, Q3: ß = 0.10, P < 0.001, and Q4: ß = 0.17, P < 0.001) even in a sex-separated analysis. Although creatinine alone was independently associated with muscle CSA (F = 5.81, P < 0.001), the association was weaker than that of CCR, particularly in the individuals with renal functional decline. Also, CCR was associated with grip strength independently of muscle CSA. CONCLUSION: CCR was a simple marker of low muscle mass and weak muscle strength in older community-dwelling adults.

Genetic factors associated with elevation of uric acid after treatment with thiazide-like diuretic in patients with essential hypertension.

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 (<1 mg/dl). Some SNPs strongly associated with an increase in UA after treatment with indapamide were identified. This study is the first report on SNPs associated with UA elevation after TD treatment. This information may be useful for the prevention of adverse effects after treatment with TD.

Effects of Collagen Hydrolysates on Human Brain Structure and Cognitive Function: A Pilot Clinical Study.

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 49-63 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'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.