Language：Japanese   Publisher：(一社)日本神経学会  

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Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1093/bbb/zbad065

PubMed

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：English   Publishing type：Research paper (scientific journal)  

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: β = -0.032, P = 0.033; Q3: β = -0.064, P < 0.001; Q4: β = -0.111, P < 0.001). In contrast, adiponectin level was independently and inversely associated with attenuation value (Q1: reference; Q2: β = -0.044, P = 0.122; Q3: β = -0.080, P = 0.006; Q4: β = -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; ••: ••-••.

DOI： 10.1111/ggi.14582

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Language：English   Publishing type：Research paper (scientific journal)  

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 (β = 0.214) and SMI (β = 0.260) as independent factors of mid-thigh muscle cross-sectional area (P < 0.001), while leg PhA (β = 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.

DOI： 10.1016/j.clnu.2023.03.016

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Language：English  

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.

DOI： 10.3389/fgene.2023.1155998

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Language：Japanese   Publisher：愛媛医学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：English   Publisher：(一社)日本脳神経超音波学会  

下顎窓から測定した、内頸動脈(ICA)における脳血管反応性(CVR)診断の有用性について検討した。有効な側頭窓が確認された健常者25例(男性13例、女性12例、平均年齢39.9±13.7歳)を対象に、息こらえ試験を行い、CVR指標としてbreath holding index(BHI)を用い、息こらえ前後の平均血流速度からBHIを算出し、ICAで測定したBHI(BHIi)と同側中大脳動脈で測定したBHI(BHIm)との相関性を評価した。その結果、BHImおよびBHIiはそれぞれ平均0.93±0.29および平均0.92±0.32で、BHImとBHIiのSpearman相関係数は0.665であった。また、BHImにより決定されたCVR障害に対するBHIiのカットオフポイントは0.71で、感度と特異度はともに80%得られた。以上の結果から、側頭窓からの測定が不十分である場合には、下顎窓からのBHI測定が代替測定として有用であることが明らかにされた。

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J02558&link_issn=&doc_id=20220113570003&doc_link_id=%2Fcn7neuro%2F2021%2F003403%2F003%2F0142-0147%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcn7neuro%2F2021%2F003403%2F003%2F0142-0147%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本老年医学会  

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.msard.2021.103135

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1016/j.jamda.2021.07.029

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Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1161/JAHA.120.018626

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.jamda.2021.06.033

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Language：English   Publishing type：Research paper (scientific journal)  

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 < 5 × 10-8), 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.

DOI： 10.1038/s41588-021-00852-9

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Language：Japanese   Publisher：日本脳神経超音波学会・日本栓子検出と治療学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：English   Publishing type：Research paper (scientific journal)  

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: 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. 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.

DOI： 10.1016/j.jamda.2021.03.021

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Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1186/s13256-020-02616-1

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Language：English  

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.

DOI： 10.1016/j.ensci.2020.100291

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経治療学会  

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Language：Japanese   Publisher：(一社)日本神経治療学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本認知症学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1089/rej.2020.2343

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Serdi-Editions  

Objectives: 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. Design: A cross-sectional analysis. Setting: 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). Measurement: 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. Results: 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 &lt
0.001) even in a sex-separated analysis. This association was independent of major covariates (Q1: β = −0.126, P &lt
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. Conclusion: The CCR may be used as a simple marker of bone property independently of muscle mass in a general population with preserved renal function.

DOI： 10.1007/s12603-020-1315-6

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is an autosomal dominant neurodegenerative disorder caused by mutations in the colony-stimulating factor 1 receptor (CSF1R) gene. We, herein, report the first Japanese case of ALSP caused by a de novo p.Phe849del mutation in CSF1R: a 44-year-old man who presented callosal disconnection symptoms. Brain MRI revealed dilation of the lateral ventricles, periventricular white matter hyperintensities, and thinning of the corpus callosum with hyperintensities on T2-weighted and FLAIR images. Brain single photon emission computed tomography (SPECT) showed hypoperfusion in the anterior corpus callosum. White matter lesions in MRI and hypoperfusion in SPECT increased with age. A brain biopsy at 44 years revealed axonal spheroids. Callosal disconnection symptoms and hypoperfusion in the anterior corpus callosum may be important indicators of ALSP, especially when caused by a p.Phe849del CSF1R mutation.

DOI： 10.1111/ncn3.12367

Web of Science

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経治療学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：English   Publishing type：Research paper (scientific journal)  

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: β = 0.06, P < 0.001, Q3: β = 0.10, P < 0.001, and Q4: β = 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.

DOI： 10.1016/j.clnu.2019.07.027

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.24659/gsr.6.2_75

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.

DOI： 10.1038/s41467-018-07345-0

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Language：Japanese   Publisher：(一社)日本神経治療学会  

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Language：Japanese   Publisher：(一社)日本脳神経超音波学会  

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Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1038/s41598-018-26908-1

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Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1038/s41440-018-0021-9

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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.

DOI： 10.1080/09168451.2018.1434406

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Yonsei University College of Medicine  

Purpose: Although time-of-flight (TOF)-magnetic resonance angiography (MRA) can clearly depict intracranial arteries, the arterial flow of middle cerebral artery (MCA) is occasionally not detected. We evaluated this phenomenon with reference to cerebrovascular dynamics. Materials and Methods: Seventeen patients with suspected occlusion of MCA or internal carotid artery on TOF-MRA were enrolled. All patients underwent CT angiography (CTA) and quantitative cerebral blood flow (CBF) examination for measurement of resting CBF and cerebrovascular reactivity (CVR). Depending on appearance, patients were categorized into three groups. Group A (n=6) had MCA delineation on both MRA and CTA, while groups B (n=6) and C (n=5) had no signal on MRA, but Group B had a MCA delineation on CTA. Results: No significant difference between resting CBF and CBF after the administration of acetazolamide was seen among 3 groups. In contrast, mean CVR in group B was -19.7±18.1%, which was significantly lower than group A [36.4±21.7% (p&lt
0.05)], but not than group C (21.4±35.2%). Furthermore, all patients in group B displayed a so-called steal phenomenon. Conclusion: This study is the first to show that visualization of MCA on TOF-MRA closely correlates with CVR, and that a vascular pattern showing no MCA signal intensity on MRA but with MCA delineation on CTA indicates a critical cerebrovascular condition.

DOI： 10.3349/ymj.2018.59.1.80

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Life Science Publishing Co. Ltd  

Objectives Although vaccination is effective method to prevent influenza infection, current influenza vaccines have inadequate efficacy in general populations. For these reasons a supplement that prevent influenza infection is keenly anticipated. In basic research, it is demonstrated that kuromoji (Lindera umbellate Thunb.) extract has an effectiveness preventing influenza infection. The aim of this study was to assess whether kuromoji extract has a protective effect on influenza infection in clinical settings. Methods In a randomized, double-blind, placebo-controlled, parallel-group study, 135 adult volunteers, they are healthy nursing staff and are met inclusion and exclusion criteria, partici-pated in this study. Sixty-seven participants received test candy (containing 67 mg/day of kuromoji extract), and another 68 participants received placebo candy. Results Test candy significantly reduced influenza infection after 12 weeks compared with placebo candy. Conclusions This is the first clinical study to assess the effectiveness of kuromoji extract in the prevention of influenza infection. Our results suggest that kuromoji extract is a safe supplement for the prevention of influenza infection.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

AimIt 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.
MethodsThe 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).
ResultsOverall, 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 ( = 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).
ConclusionsCompared with equol non-producers, equol producers showed an apparent beneficial effect in cognitive function after soy intake. Geriatr Gerontol Int 2017; 17: 2103-2108.

DOI： 10.1111/ggi.13029

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science  

Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes. Methods &amp
findings: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04–1.06, per HbA1c-raising allele, p = 3 × 10−29)
whereas GS-E was not (OR = 1.00, 95% CI 0.99–1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66–0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38–0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI 0.55–0.74) of African American adults with T2D to remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants. Conclusions: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.

DOI： 10.1371/journal.pmed.1002383

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DOI： 10.1002/jcsm.12195

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

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.

DOI： 10.1002/jcsm.12195

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Language：Japanese   Publisher：愛媛医学会  

われわれは2006年から開始している抗加齢ドックのデータを基にした加齢に伴う認知症発症リスクに対する検討を行っている。根本的な治療薬のない現在「可能な限り早期に認知症および認知症予備群を発見して適切な生活への介入を行うこと」が求められている。近年、正常加齢と認知症の境界領域と考えられる軽度認知障害(Mild cognitive impairment:MCI)が注目されており、MCIと関連するファクターを探索し、それらに対する介入を試みることは臨床面からも有用であると考えられる。MCIは65歳以上の高齢者の約5%にみられ、年間約10-15%がADに移行することが知られている。われわれはMCIの診断には「MCI screen」を用いている。このテストを用いて2017年に2本の論文がpublishされた。論文1)高齢者のMCI診断におけるSAFの有用性 AGEs(Accumulation of advanced glycation endproducts)の蓄積と認知症の発症の関連性が示唆されている。しかしながら認知症発症の前段階と考えられるMCI(mild cognitive impairment)とAGEsの関連を検討した報告は少ない。そこで本研究では健常高齢者におけるMCIと皮膚に蓄積したAGEsとの関連について検討した。本研究から非侵襲的なAGEs測定法であるSAFは健常者におけるMCIスクリーニングを行う上で有用なバイオマーカーである可能性が示唆された。論文2)高齢者におけるエクオール産生能と認知機能低下の関連 豆イソフラボン摂取による心血管疾患の予防効果が知られているが、認知機能予防効果については愚論のあるところである。個人差がある原因として大豆イソフラボンの代謝産物である「エクオール」(Equol)産生能の有無が関連している可能性がある。本研究結果からは1)エクオール産生者では有意にタッチパネル式認知機能検査の点数が高い2)エクオール非産生者では有意にMCIの存在率が高い、ことからエクオール産生者では認知機能の予防効果がある可能性がある。(著者抄録)

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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 <5% to >42% and the 5-year growth risk from <9% to >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.

DOI： 10.1212/WNL.0000000000003865

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

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 (&lt;32.5 kg in men, &lt;19.5 kg in women), and short one-leg standing time (&lt;20 seconds). These can be easily measured in the clinician's office when seeing patients. We investigated the possible association between SF score and mild cognitive impairment (MCI) in a cross-sectional study with 838 independent middle-aged to elderly participants (319 men, mean age 65.1years). In total, 118 participants were diagnosed with MCI. A SF score of 2 was significantly associated with the presence of MCI (odds ratio 4.6, 95% confidence interval: 1.9-6.9, p = 0.0001) even after adjustment for age and sex. Stepwise regression analyses showed that a SF score of 2 was associated with the presence of MCI, independently of central pulse pressure and silent cerebral infarcts. These findings indicate that the SF score is a useful frailty parameter to predict MCI in an apparently independent population.

DOI： 10.1038/srep46419

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：IOS PRESS  

Background: Accumulation of advanced glycation endproducts (AGEs) is thought to be involved in the pathogenesis of dementia, especially Alzheimer's disease. Tissue AGE accumulation can be estimated using the relative simple noninvasive measurement of skin autofluorescence (SAF), a method based on the fluorescent properties of some AGEs. However, possible involvement of tissue AGE accumulation in mild cognitive impairment (MCI) has not been fully investigated.
Objective: We investigated whether tissue AGE accumulation estimated by SAF is associated with mild cognitive impairment.
Methods: We analyzed 226 community-dwelling subjects. In addition to several atherosclerosis-related clinical parameters, MCI screening test, assessment of brain atrophy, and SAF were performed on people aged &gt; 40 years. MCI was assessed using the Japanese version of the MCI screening method. Atrophy of the brain was assessed by examining the temporal horn area (THA) by brain MRI.
Results: SAF was significantly higher in participants with MCI than in those with normal cognitive function (2.56 +/- 0.55 versus 2.10 +/- 0.41; p &lt; 0.001). Logistic regression analyses with adjustment for confounding factors including age and THA showed that high SAF &gt; 2.27 was significantly related to the presence of MCI (odds, 6.402; 95% CI, 1.590-25.773, p = 0.009).
Conclusion: We found an association between SAF and MCI, which was independent of brain atrophy, in healthy subjects.

DOI： 10.3233/JAD-160917

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OBJECTIVE: Loss of the nocturnal blood pressure (BP) drop is a risk factor for cardiovascular outcomes. However, clinical parameters that predispose to changes in nocturnal BP are currently uncertain. Given the possible involvement of salt sensitivity in nocturnal BP levels, we investigated a hypothesized association between plasma B-type natriuretic peptide (BNP) levels - a marker of body fluid retention - and nocturnal BP in a general population. METHODS: Study participants were 1020 general individuals. Participants were divided into four groups (riser, nondipper, dipper, and extreme dipper) by their percentage changes in nocturnal SBP measured using an ambulatory BP monitor. RESULTS: Plasma BNP levels were positively associated with circadian BP change (β = 0.162, P < 0.001) independently of carotid hypertrophy (β = 0.133, P < 0.001), and awake heart rate (β = -0.102, P = 0.001) and SBP (β = -0.246, P < 0.001). Risers showed 1.6 times higher BNP levels than dippers, whereas oxygen desaturation during sleep was frequently observed in nondippers. Results of multinomial logistic regression analysis indicated that BNP level was a significant determinant for the riser pattern [odds ratio (OR) 1.27 (BNP 10 pg/ml), P < 0.001], whereas oxygen desaturation was specifically associated with the nondipping pattern (OR 1.04, P = 0.001). When participants were subdivided by BNP level, risers were more frequent in the high BNP subgroup (19.5%) than in the low BNP subgroup (6.7%) (OR 3.39, P < 0.001). CONCLUSION: A slight increase in plasma BNP level was independently associated with rising nocturnal BP. Our results may help to understand the pathophysiology of circadian BP variation, and be a clue to identify individuals who require careful BP monitoring.

DOI： 10.1097/HJH.0000000000001104

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本認知症学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：日本神経免疫学会  

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Language：Japanese   Publisher：日本神経免疫学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: 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. METHOD AND RESULTS: 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. CONCLUSIONS: 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.

DOI： 10.1016/j.ijcard.2016.04.135

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DOI： 10.1038/hr.2016.43

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Early detection of pathological changes in the vasculature is required to identify individuals at risk of cardiovascular diseases. Noninvasive measurement of the second derivative of photoplethysmogram (SDPTG) might aid in evaluating vascular aging. Here we clarified the diagnostic significance of four SDPTG indices for end-organ damage. A total of 1613 community residents (65±10 years) were enrolled. Changes in blood flow volume at the forefinger were measured by photoplethysmography. SDPTG was computationally calculated from the plethysmogram, and the height of five peaks (a-e) on the SDPTG was measured. Carotid intima-media thickness (IMT), brachial-to-ankle pulse wave velocity (baPWV) and silent cerebral lesions were used as indices of end-organ damage. Multivariate analysis identified age, sex, systolic blood pressure and heart rate as strong determinants for the evaluated SDPTG indices, namely b/a, d/a and aging index ([b-d-c-e]/a). In addition, poor glycemic control and carotid IMT were also weakly associated with the SDPTG indices. Compared with other established risk factors, however, the association between the SDPTG indices and carotid IMT was weak or insignificant (b/a: β=0.069, P=0.002; d/a: β=-0.009, P=0.669; and aging index: β=0.047, P=0.037). Further, no significant association was noted between the SDPTG indices and silent lacunar infarction (b/a: P=0.111; d/a: P=0.263; and aging index: P=0.167) and periventricular hyperintensity (b/a: P=0.587; d/a: P=0.254; and aging index: P=0.429). Although the SDPTG indices evaluated here might represent structural and functional changes in arteries, they exhibited limited diagnostic significance for pathophysiological changes in large arteries, as well as small vessel diseases of the brain.

DOI： 10.1038/hr.2016.18

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

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 middleaged 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.

DOI： 10.1111/srt.12223

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Resistin is a cytokine inducing insulin resistance in mice. We previously identified single nucleotide polymorphisms (SNPs) at -420 (rs1862513) and -358 (rs3219175) located in the human resistin gene (RETN) promoter as strong determinants for circulating resistin in the Japanese population. The objective was to identify additional functional variants for circulating resistin. We conducted a genome-wide association study in 448 Japanese subjects. A peak association signal was found on chromosome 19 where RETN is located. The top-hit SNP was SNP -358 G>A, followed by rs1423096 C>T, SNP -420 C>G, and rs10401670 C>T (P = 5.39×10-47, 1.81×10-22, 2.09×10-16, and 9.25×10-15, respectively). Meta-analysis including another two independent general Japanese populations showed that circulating resistin was most strongly associated with SNP-358, followed by SNP-420, rs1423096, and rs10401670. Rs1423096 and rs10401670 were located in the 3'-region of RETN and were in strong linkage disequilibrium. Although these SNPs were also in linkage disequilibrium with the promoter SNPs, conditional and haplotype association analyses identified rs1423096 and rs10401670 as independent determinants for circulating resistin. Functionally, nuclear proteins specifically recognized T but not C at rs10401670 as evidenced by an electrophoretic mobility shift assay. The promoter activity of a luciferase reporter with T at either rs1423096 or rs10401670 was lower than that with C in THP-1 human monocytes. Therefore, rs1423096 and rs10401670, in addition to SNP-420 and SNP-358, were identified as possible functional variants affecting circulating resistin by the genome-wide search in the Japanese population.

DOI： 10.1152/physiolgenomics.00040.2016

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Language：Japanese   Publisher：(一社)日本神経学会  

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We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.

DOI： 10.1038/ng.3405

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Other Link： http://orcid.org/0000-0001-6508-4338

Language：Japanese   Publisher：(一社)日本老年医学会  

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DOI： 10.1212/WNL.0000000000001797

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Language：Japanese   Publisher：(一社)日本美容皮膚科学会  

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DOI： 10.1097/HJH.0000000000000394

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BACKGROUND AND PURPOSE: Asymptomatic cerebral small-vessel disease (cSVD) in elderly individuals are potent risk factors for stroke. In addition to common clinical risk factors, postural instability has been postulated to be associated with cSVD in older frail patients. Here, we conducted a cross-sectional study to understand the possible link between postural instability and asymptomatic cSVD further, namely periventricular hyperintensity, lacunar infarction, and microbleeds, as well as cognitive function, in a middle-aged to elderly general population (n=1387). METHODS: Postural instability was assessed based on one-leg standing time (OLST) and posturography findings. cSVD was evaluated by brain MRI. Mild cognitive impairment was assessed using a computer-based questionnaire, and carotid intima-media thickness as an index of atherosclerosis was measured via ultrasonography. RESULTS: Frequency of short OLST, in particular <20 s, increased linearly with severity of cSVD (lacunar infarction lesion: none, 9.7%; 1, 16.0%; >2, 34.5%; microbleeds lesion: none, 10.1%; 1, 15.3%; >2, 30.0%; periventricular hyperintensity grade: 0, 5.7%; 1, 11.5%; >2, 23.7%). The association of short OLST with lacunar infarction and microbleeds but not periventricular hyperintensity remained significant even after adjustment for possible covariates (lacunar infarction, P=0.009; microbleeds, P=0.003; periventricular hyperintensity, P=0.601). In contrast, no significant association was found between posturographic parameters and cSVD, whereas these parameters were linearly associated with OLST. Short OLST was also significantly associated with reduced cognitive function independent of covariates, including cSVD (P=0.002). CONCLUSIONS: Postural instability was found to be associated with early pathological changes in the brain and functional decline, even in apparently healthy subjects.

DOI： 10.1161/STROKEAHA.114.006704

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BACKGROUND AND PURPOSE: Arterial stiffness, a risk factor of brain small vessel diseases (SVD), causes hemodynamic changes. Mechanical stresses, circumferential wall tension (WT), and shear stress (SS) may change with arterial stiffness and be related to SVD. We investigated the associations between mechanical stresses and arterial stiffness and SVD. METHODS: A total of 1296 subjects without apparent cardiovascular diseases were recruited. Brachial-to-ankle pulse wave velocity (baPWV) was measured as an arterial stiffness index. Silent lacunar infarction and deep subcortical white matter hyperintensity were evaluated as SVD indices. Circumferential WT and SS at peak systole and end diastole were measured at the common carotid artery. Second peak of systolic blood pressure was obtained from the radial waveform and used as a central systolic blood pressure substitute. RESULTS: baPWV was associated positively with WT (P<0.0001) and negatively with SS (P=0.0007) even after correction for confounding parameters including baPWV. SVD was associated with significantly higher WT (P<0.0001) and lower SS (P<0.0001). After adjustment for confounding parameters (including baPWV), second peak of systolic blood pressure WT (odds ratio, 1.30; P=0.0017) and end diastolic WT (odds ratio, 1.60; P=0.0038) were related to presence of silent lacunar infarction, whereas peak systolic (odds ratio, 0.95; P=0.014) and end diastolic SS (odds ratio, 0.94; P=0.014) were associated with presence of deep subcortical white matter hyperintensity grade >3. Regression lines between blood pressure and WT were significantly steeper in subjects with SVD than without SVD (β=0.02; P<0.0001). CONCLUSIONS: These findings indicate that SVD is phenotype-specifically associated with alterations in WT and SS independently of arterial stiffness.

DOI： 10.1161/STROKEAHA.114.006539

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOLIFE SAS  

Alanine:glyoxylate aminotransferase 2 (AGXT2; EC 2.6.1.44) degrades asymmetric dimethylarginine (ADMA), a competitive inhibitor of nitric oxide (NO) synthase. Increased ADMA, reduced NO, and hypertension are shown in Agxt2 knockout mice. There are four single nucleotide polymorphisms (rs37370, rs37369, rs180749, and rs16899974) with which AGXT2 activity changes in humans and may be related to vulnerability of vascular sclerosis. To examine the relationship between them, we studied the functional haplotypes of the AGXT2 gene and decided their relationship with arteriosclerotic changes via carotid intima-media thickness (carotid IMT) in Japanese subjects. Genotyping of those polymorphisms and the carotid IMT in 1,426 Japanese subjects were then evaluated. Subjects with C-A-A-A haplotype (rs37370, rs37369, rs180749, rs16899974) showed low AGXT2 activity (P &lt; 0.0001; Pearson's correlation coefficients: 0.497). The C-A-A-A haplotype was significantly associated with mean carotid IMT (P = 0.049) and max carotid IMT (P = 0.004); Subjects with two C-A-A-A haplotypes exhibited thicker mean carotid IMT (P = 0.022) and maximum carotid IMT (P = 0.001). In multiple regression analysis, subjects with two C-A-A-A haplotypes were independently and positively associated with mean carotid IMT (P = 0.02) and maximum IMT (P = 0.005) after correction. There was a significant correlation between the functional variants in the AGXT2 gene and carotid IMT in Japanese. The AGXT2 genotype may be an important factor underlying atherosclerosis.

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective: Osteoporosis and atherosclerosis are the two most common diseases in postmenopausal women. In most cases, they are simultaneously present in the same individual and commonly lead to bone fracture or cardiovascular disease (CVD). Bisphosphonates (BPs) are frequently used in the treatment of osteoporosis and have the ability to increase lumbar spine bone mineral density (L-BMD). BPs may also protect against CVD. A single monthly 50-mg dose of minodronate (monthly minodronate) is now common practice and is highly anticipated to reduce the incidence of both bone fracture and CVD. A useful approach to independently predicting CVD is brachial-ankle pulse wave velocity (baPWV). Here, we directly compared the effects of monthly minodronate with those of a standard single weekly 35-mg dose of alendronate (weekly alendronate) on L-BMD and baPWV in postmenopausal women with osteoporosis across a 12-month period.
Methods: Thirty-eight postmenopausal women with osteoporosis were randomized into two treatment groups (group 1, weekly alendronate, n = 19; group 2, monthly minodronate, n = 19). L-BMD and baPWV were assessed at baseline and 12-month follow-up.
Results: At the end of the 12-month period, increases in L-BMD were similar between group 1 (7.6%) and group 2 (8.5%), but baPWV was significantly reduced in group 2 compared with group 1. The change in baPWV during the study period showed a significant negative correlation with the change in L-BMD.
Conclusions: Changes in L-BMD in the monthly minodronate and weekly alendronate groups are generally comparable. Good control of changes in L-BMD in the postmenopausal phase might be associated with regression of CVD. Monthly minodronate is a promising new BP and potential first-line drug for the treatment of osteoporosis in postmenopausal women.

DOI： 10.1097/gme.0000000000000197

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A paradoxical negative association between obesity and the plasma B-type natriuretic peptide (BNP) level has been firmly established. An individual's fat mass increases and muscle mass decreases with aging. Because aging is a potent determinant of plasma BNP levels, BNP may be related not only to fat mass but also to muscle mass. However, no studies have evaluated the associations between body composition and plasma levels of BNP. We performed a cross-sectional study to investigate these associations in 1,431 apparently healthy middle-aged to elderly subjects. The abdominal visceral fat area and thigh muscle cross-sectional area (CSA) were quantified by computed tomography. Plasma adiponectin and leptin levels were measured as possible confounding parameters. The brachial-ankle pulse wave velocity was measured as an index of arterial stiffness, and the pulse pressure (PP) of the second peak of the radial systolic blood pressure waveform (PP2) was used as an estimate of the central PP. Plasma BNP levels were significantly and negatively associated with the visceral fat area (r = -0.13, p <0.0001) and thigh muscle CSA (r = -0.25, p <0.0001). Corrections with possible confounding parameters including age, gender, heart rate, mean blood pressure, body weight, body height, adiponectin, leptin, brachial-ankle pulse wave velocity, and PP2 eliminated the association of BNP with visceral fat area but not with thigh muscle CSA (β = -0.27, p <0.0001). These findings indicate that along with adiposity, muscle mass is an independent determinant of plasma BNP.

DOI： 10.1016/j.amjcard.2014.05.050

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: The relationship between plasma levels of adiponectin and cardiovascular events is inconclusive. We evaluated the clinical characteristics of people with high plasma adiponectin and high plasma leptin levels. METHODS: Thousand seven hundred participants recruited from visitors to the Anti-Aging Doc were divided into four groups by combining the bipartiles of plasma adiponectin and leptin levels in men and women separately: AL, high adiponectin and high leptin; Al, high adiponectin and low leptin; al, low adiponectin and low leptin; aL, low adiponectin and high leptin. Body composition, including visceral fat area and thigh muscle cross-sectional area (CSA), brachial-ankle pulse wave velocity (baPWV), periventricular hyperintensity, and urinary albumin excretion, were determined. RESULTS: Twenty percent of the studied population fell within the AL group. This group had a significantly higher visceral fat area than the Al group. Thigh muscle CSA was lowest in the AL group among groups. baPWV, brain white matter lesions, and albuminuria findings in the AL group were significantly higher than those of the Al group. Multiple and logistic regression analyses with confounding parameters further confirmed that plasma adiponectin was not an independent determinant for brain and renal small vessel-related disease. CONCLUSION: These findings suggest that the plasma level of adiponectin alone is not enough for the risk stratification of cardiovascular disease. Leptin resistance associated with skeletal muscle loss in addition to obesity may need to be addressed to identify high risk people with high plasma adiponectin levels.

DOI： 10.1016/j.atherosclerosis.2014.05.940

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DOI： 10.1016/j.ijcard.2014.03.194

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Language：English   Publisher：AMER DIABETES ASSOC  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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OBJECTIVE: Increasing blood pressure (BP) variability is reported to be a cardiovascular risk factor. However, the clinical implications of postprandial hypotension (PHYPO), a commonly observed BP variability in elderly persons, are poorly understood. Here, we investigated the possible associations between postprandial BP decline and asymptomatic cerebral damage in community residents. METHODS: Study participants consisted of 1308 general community residents (65 ± 9 years old). Postprandial BP change was calculated from SBP measured just before and 30 min after lunch. PHYPO was defined as a decline in SBP of more than 20 mmHg. The presence of asymptomatic cerebrovascular damage was evaluated by brain MRI. RESULTS: Prevalence of lacunar infarction was significantly higher in participants with PHYPO (P = 0.004). A postprandial decline in SBP was linearly increased with the number of lacunar lesions (none, n = 1200, -3.4± 11.3 mmHg; one lesion, n = 82, -5.2 ± 11.8; two lesions, n = 18, -6.9 ± 11.5; three lesions, n = 7, -13.4 ± 11.3; and four lesions, n = 1, -27; P = 0.012). Although participants with PHYPO were older (P < 0.001) and had higher preprandial BP (P < 0.001) and faster pulse wave velocity (P = 0.001), multivariate analysis adjusted for these covariates indicated that postprandial BP decline was an independent determinant for the number of lacunar infarctions (P = 0.004). No significant associations were observed with grade of periventricular hyperintensity or frequency of microbleeds. These relationships were also found in an analysis based on central BP, whereas no superiority was seen in the analysis based on central BP. CONCLUSION: Postprandial BP decline is an overlooked risk marker for asymptomatic lacunar infarction in community residents.

DOI： 10.1097/HJH.0000000000000150

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(株)先端医学社  

われわれの施設では動脈硬化の進展度(血管年齢)の評価を中心としたアンチエイジングドックをおこなっている。これまで蓄積されたデータから血圧関連の新知見として(1)MRIで診断される無症候性微小脳出血(CMBs)が高血圧性臓器障害の1つとして考えられ、CMBsが存在する場合には将来の脳卒中の予防のためにより積極的な降圧治療が重要となること、(2)24時間自由行動下血圧測定(ABPM)で夜間血圧変動異常があると診断された場合、夜間血圧変動正常の場合とくらべて軽度認知障害(MCI)の存在するリスクが高いこと、などを報告している。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Blood levels of adiponectin, an adipocyte-secreted protein correlated with metabolic and cardiovascular risks, are highly heritable. Genome-wide association (GWA) studies for adiponectin levels have identified 14 loci harboring variants associated with blood levels of adiponectin. To identify novel adiponectin-associated loci, particularly those of importance in East Asians, we conducted a meta-analysis of GWA studies for adiponectin in 7827 individuals, followed by two stages of replications in 4298 and 5954 additional individuals. We identified a novel adiponectin-associated locus on chromosome 10 near WDR11-FGFR2 (P 3.0 10(14)) and provided suggestive evidence for a locus on chromosome 12 near OR8S1-LALBA (P 1.2 10(7)). Of the adiponectin-associated loci previously described, we confirmed the association at CDH13 (P 6.8 10(165)), ADIPOQ (P 1.8 10(22)), PEPD (P 3.6 10(12)), CMIP (P 2.1 10(10)), ZNF664 (P 2.3 10(7)) and GPR109A (P 7.4 10(6)). Conditional analysis at ADIPOQ revealed a second signal with suggestive evidence of association only after conditioning on the lead SNP (P-initial 0.020; P-conditional 7.0 10(7)). We further confirmed the independence of two pairs of closely located loci (2 Mb) on chromosome 16 at CMIP and CDH13, and on chromosome 12 at GPR109A and ZNF664. In addition, the newly identified signal near WDR11-FGFR2 exhibited evidence of association with triglycerides (P 3.3 10(4)), high density lipoprotein cholesterol (HDL-C, P 4.9 10(4)) and body mass index (BMI)-adjusted waisthip ratio (P 9.8 10(3)). These findings improve our knowledge of the genetic basis of adiponectin variation, demonstrate the shared allelic architecture for adiponectin with lipids and central obesity and motivate further studies of underlying mechanisms.

DOI： 10.1093/hmg/ddt488

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Language：English   Publishing type：Research paper (scientific journal)  

Variants in the CDH13 gene have been identified as determinants of blood levels of adiponectin, an insulin-sensitizing adipokine. However, their association with other metabolic risk factors remains unclear. We examined variants at CDH13 in relation to total and high-molecular-weight (HMW) adiponectin using data from a genome-wide association study performed in 2,434 Singaporean Chinese with replication in up to 3,290 Japanese and 1,610 Koreans. The top signal rs4783244 in CDH13 showed strong associations with total adiponectin (standardized β [β] = -0.34, 95% CI -0.38 to -0.30, P = 2.0 × 10(-70)), HMW adiponectin (β = -0.40, 95% CI -0.43 to -0.36, P = 1.1 × 10(-117)), and the HMW-to-total adiponectin ratio (β = -0.44, 95% CI -0.49 to -0.40, P = 3.2 × 10(-83)). In the replication study, this single nucleotide polymorphism explained 4.1% of total and 6.5% of HMW adiponectin levels. No association was observed between rs4783244 and metabolic traits associated with insulin resistance before adjustment for HMW adiponectin levels. After adjustment for HMW adiponectin levels, the minor allele was associated with lower BMI (β = -0.15, 95% CI -0.19 to -0.11, P = 3.5 × 10(-14)), homeostasis model assessment-insulin resistance index (β = -0.16, 95% CI -0.20 to -0.12, P = 9.2 × 10(-16)), and triglycerides (β = -0.16, 95% CI -0.19 to -0.12, P = 1.3 × 10(-16)) and with higher HDL (β = 0.16, 95% CI 0.12 to 0.19, P = 2.1 × 10(-17)). CDH13 variants strongly influence plasma total and HMW adiponectin levels in East Asian populations but appear to alter adiponectin sensitivity, resulting in better metabolic health than expected based on circulating adiponectin levels.

DOI： 10.2337/db13-0129

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Language：Japanese   Publisher：(株)医薬情報研究所  

バルプロ酸ナトリウム(バルプロ酸)投与中の脳卒中後遺症患者における血中アンモニア濃度について検討した。脳卒中発症後に、てんかん発作の予防的で6ヵ月以上バルプロ酸を内服している26例を対象とした。バルプロ酸の投与量は200〜800mg/日の通常使用量であった。バルプロ酸血中濃は平均37.9±17.0μg/mL(最高値61.1μg/mL)と基準値内であった。2例に血中アンモニア濃度の基準値上限である86μg/dLを超える高アンモニア血症を認めたが、血中アンモニア濃度は140μg/dL未満で、疲労感・傾眠・食欲不振などの症状はなかった。バルブロ酸投与量およびバルプロ酸血中濃度と血中アンモニア濃度との間には有意な相関はなかったが、血清中性脂肪および血清クレアチニン(Cr)とは有意な正の相関、血清HDL-Cとは有意な負の相関を認めた。ステップワイズ重回帰分析で、血清中性脂肪および血清Crを抽出した。

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：English   Publisher：Oxford University Press  

DOI： 10.1093/ajh/hpt052

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Accumulation of visceral fat increases cardiovascular mortality in industrialized societies. However, during the evolution of the modern human, visceral fat may have acted as energy storage facility to survive in times of famine. Therefore, past natural selection might contribute to shaping the variation of visceral fat accumulation in present populations. Here, we report that the gene encoding tribbles homolog 2 (TRIB2) influenced visceral fat accumulation and was operated by recent positive natural selection in East Asians. Our candidate gene association analysis on 11 metabolic traits of 5,810 East Asians revealed that rs1057001, a T/A transversion polymorphism in 3'untranslated region (UTR) of TRIB2, was strongly associated with visceral fat area (VFA) and waist circumference adjusted for body mass index (P = 2.7 × 10(-6) and P = 9.0 × 10(-6), respectively). rs1057001 was in absolute linkage disequilibrium with a conserved insertion-deletion polymorphism in the 3'UTR and was associated with allelic imbalance of TRIB2 transcript levels in adipose tissues. rs1057001 showed high degree of interpopulation variation of the allele frequency; the low-VFA-associated A allele was found with high frequencies in East Asians. Haplotypes containing the rs1057001 A allele exhibited a signature of a selective sweep, which may have occurred 16,546-27,827 years ago in East Asians. Given the predominance of the thrifty gene hypothesis, it is surprising that the apparently non-thrifty allele was selectively favored in the evolution of modern humans. Environmental/physiological factors other than famine would be needed to explain the non-neutral evolution of TRIB2 in East Asians.

DOI： 10.1007/s00439-012-1240-9

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J-GLOBAL

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Background: Cerebral microbleeds (CMBs) detected on T2*-weighted MRI gradient-echo have been associated with increased risk of cerebral infarction. We evaluated risk factors for these lesions in a cohort of first-time ischemic stroke patients.
Methods: Presence of CMBs in consecutive first-time ischemic stroke patients was evaluated. The location of CMBs was classified by cerebral region as strictly lobar (lobar CMBs) and deep or infratentorial (deep CMBs). Logistic regression analysis was performed to determine the contribution of lipid profile to the presence of CMBs.
Results: One hundred and sixteen patients with a mean age of 70 +/- 10 years were recruited. CMBs were present in 74 patients. The deep CMBs group had significantly lower HDL-C levels than those without CMBs. In univariable analysis, advanced periventricular hyperintensity grade (PVH&gt;2) and decreased HDL-C were significantly associated with the deep but not the lobar CMB group. On logistic regression analysis, HDL-C (beta= -0.06, p = 0.002) and PVH grade &gt;2 (beta = 3.40, p = 0.005) were independent determinants of deep CMBs.
Conclusions: Low HDL-C may be a risk factor of deep CMBs, including advanced PVH status, in elderly patients with acute ischemic stroke. Management of HDL-C levels might be a therapeutic target for the prevention of recurrence of stroke. (C) 2012 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2012.12.022

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Background: Although rupture of unruptured intracranial aneurysms (UIAs) is closely associated with UIA growth during follow-up, few studies have investigated how UIAs grow during observation. Hypertension appears to affect the formation of intracranial aneurysms. However, few studies have investigated the association of blood pressure variability with UIA growth. Visit-to-visit variability (VVV) in systolic blood pressure (SBP) is a newly defined concept which appears to be a good predictor of stroke. With this factor in mind, here we conducted a prospective analysis of the results of 2 years of observation of UIAs by magnetic resonance angiography (MRA) and sought to identify risk factors for UIA growth and rupture. Methods: From December 2006 through June 2010, two hundred patients with 212 UIAs were followed for 2 years. Patient ages ranged from 31 to 91 years. Putative risk factors for the growth of UIAs were evaluated. Subjects were divided into two groups: a UIA growth group consisting of patients whose UIAs increased by 1 mm or more in size or who developed subarachnoid hemorrhage (SAH), and an unchanged group. Brachial blood pressure values were recorded at the time of diagnosis and during follow-up in the outpatient clinic. All blood pressure values were then averaged, and the VVV of SBP was defined as the standard deviation (SD) of a minimum of 5 blood pressure measurements at outpatient visits. Results: UIA growth occurred in 20 patients and SAH occurred in 1 patient. Current smoking tended to be more prevalent in the UIA growth group (p &lt; 0.01). Five of the 12 patients with multiple UIAs showed UIA growth within 2 years and multiplicity was a significant risk factor for UIA growth (p &lt; 0.01). The mean baseline size in the UIA growth group was larger than that in the unchanged group (p = 0.01) and 7 of the 18 patients with large UIAs, categorized as having an initial diameter of 7 mm or more, had an increase in UIA size over the 2 years (p &lt; 0.01). On multivariable logistic regression analysis, current smoking, multiplicity, and UIA size = 7 mm were significant risk factors for UIA growth. Although no significant difference was seen between the UIA growth and unchanged groups in office SBP during the observation period, VVV in SBP was significantly higher in the UIA growth group than in the unchanged group, and it was significantly and independently associated with UIA growth. Conclusions: VVV in SBP is a novel risk factor for the growth of UIAs and may be a key factor for the prevention of UIA rupture. Future research is needed to confirm that SBP stability prevents UIA rupture. (C) 2013 S. Karger AG, Basel

DOI： 10.1159/000356217

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Elevated hematocrit levels have been suggested to be an independent determinant of insulin resistance and type 2 diabetes. To clarify the diagnostic significance of hematocrit level, we investigated the association with hemodynamic profiles, insulin resistance and insulin sensitivity, arterial properties, and asymptomatic cerebrovascular damage in a general Japanese population. METHODS: This study included 1,978 participants from two independent cohorts. Insulin sensitivity was assessed by the oral 75 g glucose tolerance test. Carotid ultrasonography was performed to evaluate atherosclerosis and wall shear stress. Periventricular hyperintensity and lacunar infarction were assessed by brain magnetic resonance imaging. RESULTS: Hematocrit quartile showed a stepwise association with insulin sensitivity (Q1: 2.2±0.7, Q2: 2.0±0.7, Q3: 1.9±0.7, Q4: 1.8±0.6, p<0.001) and insulin resistance (1.0±0.6, 1.2±0.7, 1.3±0.8, 1.5±1.0, p<0.001). Multiple linear regression analysis adjusted for possible covariates identified hematocrit as an independent determinant of insulin sensitivity (β=-0.074, p=0.019) and insulin resistance (β=0.115, p<0.001). However, this association was lost after further adjustment for visceral fat area and plasma alanine aminotransferase level. Further, no significant association was observed between hematocrit and carotid intima-media thickness (p=0.306) where as wall shear stress was inversely associated with the carotid atherosclerosis (r=-0.250, p<0.001). In contrast, a low hematocrit level was independently associated with periventricular hyperintensity (odds ratio 0.87 (95% CI 0.80-0.95), p=0.001). CONCLUSION: Hematocrit was positively associated with insulin resistance and insulin sensitivity. This association was epiphenomenon of visceral and hepatic adiposity. Conversely, low hematocrit was a significant risk factor for periventricular hyperintensity independent of insulin resistance.

DOI： 10.3233/CH-2012-1634

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Language：English  

DOI： 10.1111/j.1468-1331.2012.03879.x

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Language：English   Publishing type：Research paper (scientific journal)  

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Language：English  

DOI： 10.1097/gme.0b013e318259c04e

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DOI： 10.1111/j.1447-0594.2011.00824.x

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DOI： 10.1111/j.1532-5415.2012.04184.x

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Language：English   Publisher：Elsevier Ireland Ltd.  

DOI： 10.1016/j.atherosclerosis.2012.07.015

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CiNii Books

J-GLOBAL

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DOI： 10.1007/bf03261902

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Language：English  

DOI： 10.1016/j.ijcard.2012.04.033

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Language：Japanese   Publisher：(一社)日本抗加齢医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A 69-year-old woman was admitted because of unconsciousness and multiple cranial neuropathy. She had suffered diarrhea 2 weeks previously. On examination, she was noted to have total external and internal ophthalmoplegia, bilateral facial palsy, dysphagia, dysarthria, neck weakness, distal motor weakness of all limbs, and ataxia. She had also presented with hyporeflexia and hypoesthesia, but with a bilateral pyramidal tract sign. A study of her cerebrospinal fluid revealed albuminocytologic dissociation, and nerve conduction study revealed demyelination of her peripheral nerves. Moreover, electroencephalography findings were abnormal and anti-GQ1b antibody was positive. We diagnosed Fisher syndrome with Guillain-Barré syndrome and Bickerstaff brainstem encephalitis. We administered intravenous immunoglobulin treatment for 5 days and her symptoms gradually improved. However, her external ophthalmoplegia continued for several months.

DOI： 10.3143/geriatrics.49.367

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Background: Given the very poor outcome of ruptured intracranial aneurysms, detection and treatment of unruptured intracranial aneurysms by a less invasive examination have become important. For this purpose, 3-tesla (3T) magnetic resonance imaging (MRI) is the most suitable candidate, owing to its high signal/noise ratio and frequency resolution. However, few reports have investigated the prevalence of intracranial aneurysms with high-tesla MRI. Here, we evaluated the prevalence of intracranial aneurysms and the effectiveness of a 3T MRI system in their detection. Methods: During a 1-year period, a total of 3,414 consecutive patients undergoing MR angiography with 3T MRI for the first time were enrolled. Diagnosis of intracranial aneurysm was made by two neuroradiologically trained medical doctors under complete blinding to patient information. When intracranial aneurysm was suspected, volume-rendering images were created for more accurate diagnosis. Results: Surprisingly, 317 unruptured intracranial aneurysms were identified in 286 of 3,414 cases (8.4%); 151 unruptured aneurysms (47.6%) occurred in the internal carotid artery, 85 (26.8%) in the middle cerebral artery, 54 (17.0%) in the anterior cerebral artery, and 27 (8.5%) in the posterior circulation. Of these, 152/317 (47.9%) were &lt; 3 mm, 104 (32.8%) ranged from 3 to 5 mm, 5 (11.0%) from 5 to 7 mm, and 26 (8.2%) were &gt;7 mm. No significant difference in size was seen among the four locations. Conclusions: For the first time, this study assessed the detection rate of intracranial aneurysms using 3T MRI. Results showed a higher detection rate than previously documented. The reason for this higher rate is likely the improved ability of this modality to detect unruptured aneurysms in the internal carotid artery and those &lt;3 mm. Copyright (C) 2012 S. Karger AG, Basel

DOI： 10.1159/000336015

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DOI： 10.5551/jat.11924

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DOI： 10.1155/2012/320648

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本聴覚医学会  

当院の老年内科が「抗加齢ドック」を実施しているのに呼応し、当科でも2009年12月に「聴力ドック」を立ち上げ、抗加齢ドックと連携して予防医学的観点から加齢性難聴の研究を始めた。聴力ドック開始から7ヵ月間に、抗加齢ドック受診者216名のうち96名(44.4%)が聴力ドックを受診した。聴力ドックの受診は60歳代から増加する傾向にあり、その受診理由は「難聴の自覚」が最も多かった。抗加齢ドックで実施している脈波伝搬速度(PWV)や頸動脈内膜中膜複合体肥厚度(IMT)の結果と周波数ごとの聴力レベルとの関係を重回帰分析したところ、PWVでは8kHzの聴力レベルと、IMTは4kHzと8kHzの聴力レベルと有意な関連が認められた。この結果は、高齢者の高音域聴力低下に動脈硬化が関与していることを示唆する。(著者抄録)

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本頭痛学会  

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Language：Japanese   Publisher：(株)新興医学出版社  

●高齢者の転倒は骨折を介して生命予後に重大な影響を与える。●加齢に伴う骨格筋量減少および筋力低下は、高齢者の転倒リスクの増加(転倒しやすさ)を介して将来の身体的な機能障害のリスクとなる可能性がある。●大腿四頭筋面積の低下(sarcopenia)は転倒しやすさにつながる。●内臓脂肪面積の増加(obesity)は転倒しやすさにつながる。●大腿四頭筋面積の低下と内臓脂肪面積の増加が重複した状態(sarcopenic obesity)は転倒リスクとしてもっとも重要である。(著者抄録)

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：日本医学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(一社)日本脳神経超音波学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本抗加齢医学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

We investigated whether the on-treatment low-density lipoprotein- cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio is a predictive marker of stroke recurrence in patients with acute ischemic stroke. A total of 137 dyslipidemia patients who had suffered acute ischemic stroke were enrolled and were treated with rosuvastatin 2.5mg. During a mean follow-up of 34.9±0.8 months, there were 10 cases of stroke recurrence. Age, CKD at baseline, and an on-treatment LDL-C/HDL-C ratio &gt
2.0 after one month of rosuvastatin treatment were predictors of stroke recurrence by univariate analysis. Stepwise regression analysis showed that CKD (standardized adjusted OR 6.55 [1.18-36.43]
p = 0.030) and on-treatment LDL-C/HDL-C ratio &gt
2.0 (standardized adjusted OR 9.70 [1.70-55.33]
p = 0.011) were independent risk factors associated with stroke recurrence. These results suggest that the use of statin therapy to achieve an on-treatment LDL-C/HDL-C ratio ≤ 2.0 is a suitable treatment strategy in patients with acute ischemic stroke. In addition, post-hoc analysis indicated that more intensive lipid control, to LDL-C/HDL-C ratio ≤ 1.5, may offer additional clinical benefits
further study will be required to substantiate this point.

Scopus

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：English  

DOI： 10.3143/geriatrics.48.47

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Language：English   Publishing type：Research paper (scientific journal)  

Background: Controversy exists as to whether angiotensin (1–7) (Ang (1–7)) acts as a protective hormone against renal injury. Methods: We compared the degree of improvement of hypertensive nephropathy following 8 weeks’ treatment with either the angiotensin II receptor type 1 antagonist olmesartan medoxomil or the cardioselective beta blocker atenolol in 8-week-old spontaneously hypertensive rats (SHRs). Results: Both treatment regimens reduced mean blood pressure in a similar fashion, while bradycardia was present only in atenolol-treated SHRs. The heart weight:body weight ratio fell more in SHRs medicated with olmesartan versus those receiving atenolol. These changes were associated with increases in plasma Ang II in SHRs given the angiotensin II receptor blocker. At the end of treatment, plasma Ang (1–7) was higher in the olmesartan than atenolol or vehicle groups. The glomerular sclerosis (GS) index was lowered by olmesartan and atenolol compared with the vehicle group. While both olmesartan and atenolol attenuated renal perivascular collagen deposition (PVCD), the greatest effect was observed in SHRs receiving olmesartan. Elevations in plasma Ang (1–7) correlated negatively with reductions in GS or PVCD index, respectively. Conclusions: While control of blood pressure remains a critical factor in the prevention of hypertensive nephropathy, Ang (1–7) may play a substantial role in preventing the structural changes in glomerulus through its effect on regulations of blood pressure and renal function. © 2011, SAGE Publications. All rights reserved.

DOI： 10.1177/1753944711429343

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Publishing type：Research paper (scientific journal)   Publisher：Japan Audiological Society  

DOI： 10.4295/audiology.54.671

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DOI： 10.3143/geriatrics.48.130

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DOI： 10.1371/journal.pone.0024633

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：English  

DOI： 10.1016/j.atherosclerosis.2010.05.026

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：English  

DOI： 10.1111/j.1447-0594.2009.00565.x

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CiNii Books

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Language：Japanese   Publishing type：Research paper (scientific journal)  

J-GLOBAL

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Language：English  

DOI： 10.1159/000321985

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Language：Japanese  

DOI： 10.3143/geriatrics.47.158

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CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2010174503

Language：English  

DOI： 10.1159/000255106

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：English  

DOI： 10.3143/geriatrics.46.409

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2009&ichushi_jid=J01214&link_issn=&doc_id=20091014300009&doc_link_id=10026894248&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F10026894248&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：English  

DOI： 10.1097/HJH.0b013e328314b821

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：The Japan Geriatrics Society  

A 64-year old woman visited our outpatient clinic with chronic headache on August 30^th, 2005. She had been sufferring from migraine from her 30's. Although sumatriptan improved her symptoms, migraine attacks had occurred every other day recently. At presentation, her headache was moderate in intensity and lasted about four hours. Daily activity worsened her pulsating headache associated with nausea and vomiting. She diagnosed with migraine without aura, which met the diagnostic criterion for migraine by International Classification of Headache Disorders. Lomerizine was administered as a prophylactic agent, however it did not reduce the frequency of migraine attacks. Accordingly, lomerizine was withdrawn from November 2005. Her blood pressure gradually increased during the course, and amlodipine, 2.5 mg/day, was started for her hypertension May 2007. After starting amlodipine, she noticed a reduction in migraine attacks, only two times a month in August 2007. Assessment with the HIT-6 questionnaire showed great improvement in her QOL score for daily life. Although the underlying mechanisms have not been elucidated, amlodipine was effective in reducing migraine attacks in this patient. The findings in this case may suggest that amlodipine administration might be a useful strategy to control migraine attack.<br>

DOI： 10.3143/geriatrics.45.546

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CiNii Books

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Other Link： https://jlc.jst.go.jp/DN/JALC/00322094992?from=CiNii

Language：Japanese   Publisher：千代田開発(株)  

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Language：Japanese   Publisher：(一社)日本頭痛学会  

病院看護部勤務の看護師における慢性頭痛の現状と頭痛診療の現況をアンケート調査にて検討した。一次性頭痛は国際頭痛学会診断基準に基づき診断した。対象者中慢性頭痛が全体の37.7%であり、片頭痛の有病率は19.3%、緊張型頭痛は15.6%であった。片頭痛群では診察処方を受けている人は25.5%であり、61.7%は診察を受けず鎮痛薬を自己判断で内服していた。緊張型頭痛群では診察処方を受けている人は13.2%であり、65.8%が鎮痛薬を自己判断で内服していた。今回の調査で医療従事者での慢性頭痛の有病率、日常生活支障度の高さが認められ、受診率の低さ、自己判断での鎮痛薬内服が目立つ実態も明らかになった。(著者抄録)

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：English  

DOI： 10.1291/hypres.31.553

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Language：Japanese   Publisher：(一社)日本脳卒中学会  

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Language：Japanese   Publisher：愛媛医学会  

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Language：English  

DOI： 10.1161/HYPERTENSIONAHA.107.102046

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Language：Japanese   Publisher：(一社)日本内科学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING  

A 64-year-old man presented with high fever, deep coma, neck stiffness and decorticate rigidity on admission to our hospital. Laboratory findings revealed liver dysfunction, and serial brain computer tomography revealed a right cerebellar hematoma, a small hemorrhage in the left frontal lobe and ischemia of the left corona radiata. Electroencephalogram (EEG) showed periodic synchronous discharge (PSD) patterns on the first occasion, but these disappeared in later EEG. Based on the cerebrospinal fluid findings of increased total protein (1183 mg/dL), increased cells (71/mu L) and decreased glucose concentration (1 mg/dL), and the culture result of pure growth of Streptococcus pneumoniae, he was diagnosed as having pneumococcal meningoencephalitis. PSD patterns, though seldom found in bacterial meningoencephalitis, presented in this case probably due to severe infection of the central nervous system and hepatic encephalopathy. We report this case to emphasize that PSD can emerge on EEG in the early stage of pneumococcal meningoencephalitis.

DOI： 10.1111/j.1447-0594.2007.00431.x

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DOI： 10.3143/geriatrics.44.747

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Language：Japanese  

DOI： 10.3143/geriatrics.44.734

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Other Link： http://search.jamas.or.jp/link/ui/2008133540

Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：English  

DOI： 10.1291/hypres.30.577

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CiNii Books

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：The Japanese Society of Internal Medicine  

高齢者は健康な状態でも基礎体力や免疫能が低下しており, 多くは既存の基礎疾患があることなどにより感染症が重症化しやすい. このため初期治療の如何により予後が大きく影響されることが考えられる. 従って抗菌薬を選択する際には高齢者の特性を理解すること, 抗菌薬の投与前にその薬剤の副作用, 薬剤間相互作用に十分理解することが必要である. さらに抗菌薬の投与方法もその抗菌薬の体内動態を理解したうえで決定していく必要がある.

DOI： 10.2169/naika.95.2193

CiNii Books

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Other Link： https://jlc.jst.go.jp/DN/JALC/00287357460?from=CiNii

Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：The Japan Geriatrics Society  

A 52-year-old woman with diabetes mellitus (DM) complained of weakness of the arms and legs. She was referred to our hospital in November 2002 because of anemia, thyroid tumor and meningioma including DM. She was short in stature, juvenile bilateral cataract, intractable skin ulcers, clavus on the sole of her foot, a bird-like face and high-pitched voice. Typical physical features led to the final diagnosis of Werner's syndrome. Although the myelogram revealed no abnormal findings except erythroid hypoplasia, cytogenetic analysis of bone marrow cells showed deletion of chromosome 20 in 10% of the analyzed cells, which suggested the possibility of that myelodysplastic syndrome (MDS) or acute myeloblastic leukemia (AML) could occur. She had a thyroidectomy because both lobes of the thyroid gland were enlarged and caused hoarseness, In addition, it is common knowledge that the goiter could become malignant. We need to follow her carefully because she might be vulnerable to malignant disease, including leukemia and malignant meningioma.

DOI： 10.3143/geriatrics.43.639

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Language：Japanese   Publisher：(公社)日本人間ドック学会  

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Language：Japanese   Publisher：(株)北隆館  

長寿社会の到来に伴い,高齢者が健康長寿を過ごすことができることを目的に抗加齢医学の研究が始まった.愛媛大学では平成18年2月より抗加齢センターが設置され,自由診療で主に血管系を中心とした抗加齢ドックを開始した.平成18年5月12日現在で約100名のドックを施行し,5名に未破裂脳動脈瘤が発見され専門医への紹介を行うなど一定の成果が出ている.今後の目標は血管年齢の把握と適切な予防・治療法を確立して受診者の健康長寿達成することである(著者抄録)

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：English  

DOI： 10.1291/hypres.29.227

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Language：Japanese   Publisher：The Japan Geriatrics Society  

An 89-years-old woman had anorexia for at least 1 month, and had been given symptomatic treatment at a nearby hospital. She was admitted to our hospital on August 22, 2003, for thorough examination and appropriate treatment for lack of spontaneity and appetite loss. On admission, laboratory data revealed hyponatremia (125mEq/L) and hypoaldosteronism (0.7ng/mL). Since hyponatremia did not improve by intravenous drip with saline, we identified the major cause of her complaint as hypoaldosteronism. She was treated with fludrocortisone (0.05mg/day) and her condition improved immediately. Although she was discharged at that time, her condition shortly deteriorated. She was referred to our hospital on February 10, 2004 for medical treatment. On admission, inadequate oral intake, lack of spontaneity and weakness in her lower legs were noted. The plasma Na concentration was 127mEq/L. Nasogastric tube feeding was started to prevent aspiration pneumonia because of her dysphagia. Fludrocortisone was given (0.2mg/day), and she was able to swallow food without nasal feeding tube during the second month of therapy. Laboratory data including plasma natrium concentration were normal. Also she could perform bed-to-wheelchair transfer independently. This is a rare case of a critically ill elderly patient with hyponatremia caused by hypoaldosteronism possibly due to mineral corticoid-responsive hyponatremia of the elderly.

DOI： 10.3143/geriatrics.43.122

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(一社)日本循環器学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE SOC HYPERTENSION CENT ACADEMIC SOC, PUBL OFFICE  

Hypertension is a common, complex phenotype resulting from the interaction between genetic and environmental factors. To select candidate regions potentially responsible for hypertension, we are conducting a genome-wide linkage disequilibrium (LD) mapping of hypertension using dinucleotide repeat markers in 146 hypertensive and 136 normotensive subjects. Although the LD mapping is still underway, 19 alleles of 15 markers have already shown a nominally significant association (p&lt;0.05), with odds ratios ranging from 0.08 to 5.12, suggesting the presence of many hypertension-related loci with weak effects in the human genome. These markers should be further assessed, adjusting for confounding factors and considering gene-gene and gene-environmental interactions in additional samples. In this report, we discuss our ongoing LD mapping project and describe the 15 markers thus far discovered. Among the 15 markers, D10S537 had a highly significant association with hypertension (p=53X10(-5); OR=3.80; 95% CI=1.98-7.27; where OR indicates the odds ratio and 95% Cl indicates the 95% confidence interval). Further analysis in a large Japanese population showed that D10S537 was significantly associated with hypertension (p=0.044; OR=1.27; 95% CI=1.01-1.59). D10S537 was more significantly associated with hypertension in subjects with normotriglyceridemia in our population (p=0.007; OR=1.47; 95% CI=1.11-1.95).

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE SOC HYPERTENSION CENT ACADEMIC SOC, PUBL OFFICE  

The beta-adrenoceptor (beta-AR)-stimulatory guanine nucleotide-binding (Gs) protein system has been shown to play important roles in the cardiovascular system. The gene encoding the alpha-subunit of Gs proteins (GNAS1) is a candidate genetic determinant for hypertension. Because alcohol consumption is known to affect blood pressure partly through the beta-AR-Gs protein system, we examined the possible interaction between GNAS1 T393C polymorphism and drinking status in the association with hypertension in the present study. As a result, a non-significant but reasonable trend supporting the presence of an interaction was shown (p=0.076). In line with this trend, the T393C polymorphism significantly interacted with drinking status in the association with systolic blood pressure (p=0.028). Moreover, supporting the presence of an interaction, T allele carriers consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than CC homozygotes in non-drinkers and light drinkers. In contrast, CC homozygotes consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than T allele carriers in moderate to heavy drinkers. The present study also showed a significant interaction between the T393C polymorphism and drinking status in the association with pulse pressure (p=0.026), reflected by a significant association between the T393C polymorphism and pulse pressure in moderate to heavy drinkers (p=0.026). These findings may be helpful in conducting further molecular and biological studies on the relationship among the effects of alcohol, the beta-AR-Gs protein system, and hypertension.

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：The Japan Geriatrics Society  

With the rapid aging of Japan's population, medical professionals who specialize in geriatric medicine are in unprecedented demand. At Ehime University School of Medicine, the Department of Geriatric Medicine was established on April 1, 1997. To assess the status of geriatric medicine in undergraduate education, we surveyed the opinions of medical students on geriatric medicine. A questionnaire was sent to both fourth-year medical students before their classes on internal medicine and geriatric medicine had ended and to sixth-year medical students after their classes had already ended. Medical students of Ehime University School of Medicine had significantly more interest in geriatric medicine than students at other medical schools. From a clinical viewpoint of problems in old age, they considered that cerebrovascular disease, cardiovascular disorders, neurocognitive disorders and pulmonary disease were important. A total of 60% agreed that all medical schools should have classes in geriatric medicine, which is a higher rate than that of previous reports. To study the opinions of medical students on textbooks on geriatrics, we also conducted a questionnaire among medical students. Although 90% of students had their own textbooks of internal medicine and almost half (42%) had textbooks on physical examination, none had their own textbook of geriatric medicine. The most frequent reason was "hard to choose the best textbook". The present study indicates that to develop education in geriatric medicine, it is important to make a recommendable text book for medical students, which is easily understood with high quality and originality.

DOI： 10.3143/geriatrics.40.53

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CiNii Books

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Other Link： https://jlc.jst.go.jp/DN/JALC/00230227468?from=CiNii

Language：Japanese   Publisher：(一財)代謝異常治療研究基金  

50歳以上の一般住民200名を対象に,クラミジア・ニューモニエ抗体価を測定し,ポジティブコントロールに対する比としてindexを求め,IgA及びIgG indexが共に1.1を越える場合を陽性,1.0未満を陰性,それ以外を中間とした.その結果,陰性は57名(男12名,女45名,平均68歳;A群),中間が81名(男21名,女60名,平均70歳;B群),陽性が62名(男31名,女31名,平均72歳;C群)であった.C群は年齢が有意に高く,総コレステロール値が低く,喫煙率が高かった.又,頸動脈エコーによる内膜中膜厚及び頸動脈内径は,C群がA群に比較して有意に高値であった.血中可溶性接着因子濃度は,ICAM-1がA群392ng/ml,B群398ng/ml,C群470ng/ml,VCAM-1が各々402ng/ml,419ng/ml,472ng/mlで,C群が有意に高値であった.MCP-1には有意差がなかった.又,C群中のIgA,IgG indexが2.5を越える強陽性者は,それ以外の陽性者に比較してICAM,VCAM,MCP-1濃度がいずれも高値であった

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide produced by endothelial and smooth muscle cells. Many lines of biological evidence suggest that the ET-1 gene is a candidate gene for hypertension. Moreover, recent association studies suggested that a G/T polymorphism with an amino acid substitution (Lys/Asn) at codon 198 in exon 5 of the ET-1 gene interacts with body mass index (BMI) in association with blood pressure. They suggested that T carriers are more sensitive to weight gain than GG homozygotes in association with blood pressure. However, association studies are often irreproducible, and the first study often suggests a stronger genetic effect than is found by subsequent studies. We therefore assessed the interaction in 2 large Japanese populations. The present study showed a nonsignificant but similar trend to the results of previous reports. Moreover, in line with previous reports, this study revealed a significant interaction between the ET-1 K198N (G/T) polymorphism and BMI in association with hypertension in our populations (P=0.027). The interaction was significant, even after adjustment for gender and age (P=0.045) and for all confounding factors (P=0.044). T carriers were more sensitive to weight gain than GG homozygotes in association with hypertension. Considering the combined impact of obesity and hypertension on the development of cardiovascular and cerebrovascular disorders, T allele carriers might represent elective targets for therapy to lower their body weight.

DOI： 10.1161/01.HYP.0000043680.75107.CF

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：English   Publisher：The Japanese Society of Hypertension  

<B>Hepatocyte growth factor (HGF) has been shown to have a unique stimulating property on the endothelium as well as an anti-apoptotic action on the endothelium. Through these mechanisms, HGF has been shown to have an anti-atherogenic action in animal models. In atherosclerotic disorders, the circulating level of HGF has been shown to be increased to compensate for its decline in tissue. However, whether increased circulating HGF has any influence on the development of atherosclerosis has not been elucidated. In the present study, the association between plasma HGF concentration and the risk factor-carotid atherosclerosis relationship was evaluated. Three hundred and seventeen community-dwelling subjects participated in the study. The plasma concentration of HGF was determined by enzyme-linked immunosorbent assay (ELISA). The subjects were divided into two groups according to the plasma level of HGF: a low HGF group (<I>n</I> =199, plasma HGF <150 pg/ml) and a high HGF group (<I>n</I> =118, plasma HGF ≥150 pg/ml). Risk factors for atherosclerosis were evaluated in each subject. Carotid ultrasonography was performed to measure carotid arterial intima-media thickness (IMT) and the presence of plaque. The association between carotid IMT and risk factors was then evaluated in the two HGF groups. The regression lines between age and carotid IMT were significantly different between the low HGF and high HGF groups (<I>F</I>[1, 313]=5.98, <I>p</I> =0.015). The regression lines between systolic blood pressure and carotid IMT were also significantly different between the two HGF groups (<I>F</I> [1, 313]=5.17, <I>p</I> =0.024). A general linear model showed that the interaction between age and plasma level of HGF was significantly associated with carotid IMT, suggesting that the plasma level of HGF modifies the age-related increase in carotid IMT. In addition, clustering of risk factors was evaluated in subjects with carotid atherosclerosis. The number of total risk factors in carotid atherosclerosis subjects with high plasma HGF was significantly greater than that in those with low HGF, even though the two groups had a similar magnitude of carotid atherosclerosis. In conclusion, these findings indicate that risk factor-dependent augmentation of carotid atherosclerosis could be influenced by circulating HGF. (Hypertens Res 2002; 25: 661-667)</B>

DOI： 10.1291/hypres.25.661

PubMed

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2003078500

Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：English  

DOI： 10.3143/geriatrics.39.193

PubMed

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Language：Japanese   Publisher：(一社)日本老年医学会  

対象として愛媛県下のコホートから50歳以上の在住者全例を選定し,降圧薬等の服薬のない237例を解析対象とした.起立性血圧変化は,安静臥床時,起立1分後および3分後の収縮期血圧変化から判断した.対象者全体では,起立後の経時的血圧変化は,1分後の変動が最も大きく,3分後には前値に戻る傾向を示した.しかし,起立1分後には血圧変動異常を示さず,3分後に初めて過度の低血圧または高血圧を示した例がそれぞれ7.2%,8.4%存在した.起立性血圧変化の異常は,起立1分後の血圧測定でまず評価し,異常が認められない場合は,3分後にも再度測定することで評価する必要があることが示された

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2002&ichushi_jid=J01214&link_issn=&doc_id=20020404350017&doc_link_id=10008508457&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F10008508457&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Language：Japanese   Publisher：(一社)日本内科学会  

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Language：Japanese   Publisher：The Japan Geriatrics Society  

An 82-year-old woman was diagnosed with hypertension at the age of 50 and had been treated with antihypertensive agents. Proteinuria was detected at age 60 and her renal function subsequently deteriorated. Hemodialysis was started on February 14, 2000. She fell out of the bed and hit her neck in the early morning on February 15.<br>Neck X-ray tomography revealed Anderson type III dens fracture. Since she had several complicating conditions including angina pectoris and arrhythmia, she was treated by external fixation using a halo-vest. The neck pain improved gradually. During her clinical course, she experienced delirium due to immobilization. However, bone union was complete 5 months later.<br>Physicians should be aware of the possibility that even minor injury can cause dens fracture in elderly patients. Conservative management of type III dense fracture should be considered for elderly patients with a compromised condition.

DOI： 10.3143/geriatrics.38.825

CiNii Books

J-GLOBAL

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本内科学会  

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Language：Japanese   Publisher：The Japan Geriatrics Society  

A 60 year-old man who has suffered dysarthria since 1999. He had noticed twitching of right upper extremity and orbicularis oris muscle since August 2000. The bulbar type of amyotrophic lateral sclerosis was diagnosed. He was admitted for evaluation of sleep disorder with respiratory distress on November 20, 2000. Arterial blood gas analysis on admission showed marked hypercapnea (PaCO₂:51.6Torr). Nocturnal hypoxia index, which was calculated using the nocturnal oximetry monitoring, was elevated. Non-invasive positive pressure ventilation started during sleep at night, although it was earlier than to start for mechanical ventilation. After one week, both hypercapnea and his nocturnal hypoxia index, together with symptoms, improved markedly.<br>Respiratory insufficiency due to progressive fatigue of respiratory muscles, such as diaphragm and intercostal muscles, is a major cause of death in amyotrophic lateral sclerosis. In general mechanical ventilation is introduced when marked hypercapnea and dyspnea become clinically overt. However, the exact time to introduce noninvasive methods of ventilatory support for amyotrophic lateral sclerosis has not been established.<br>Based on the observation in this patient, we would suggest that earlier introduction of non-invasive mechanical support for ventilation (nocturnal hypoxia index>70) would be useful to improve the symptoms and to prolong the life of patients with ALS. The nocturnal hypoxia index is useful to decide the time of the introduction of non-invasive mechanical support for ventilation.

DOI： 10.3143/geriatrics.38.816

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Language：Japanese   Publisher：日本臨床分子医学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本内科学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：EXCERPTA MEDICA INC  

Increased left ventricular (LV) mass and abnormal geometry have a powerful prognostic value for cardiovascular morbidity and mortality including stroke. However, there have been no studies on the association between LV hypertrophy and preclinical brain damage in essential hypertensive patients. In the present study, we investigated the relation between LV hypertrophy and asymptomatic cerebrovascular damage identified;I by magnetic resonance imaging in 150 essential hypertensive patients, with an emphasis on LV geometry. Patients were divided into the following 4 groups according to their LV mass index and relative wall thickness; normal ventricular geometry (n = 50), concentric remodeling (n = 22), eccentric hypertrophy (n = 44), and concentric LV hypertrophy (n = 34). Lacunar lesions and leukoaraiosis were evaluated. The prevalence of lacunae was significantly higher in patients with LV remodeling than in patients with normal LV (chi-square 19.6, p = 0.0002). The number of lacunae was significantly higher in patients with LV hypertrophy than in patients with normal LV or concentric remodeling (F [3,146] = 8.03, p&lt;0.0001). The severity of leukoaraiosis was also significantly greater in patients with LV hypertrophy than in patients with a normal left ventricle (chi-square 14.5, p = 0.02). Stepwise regression analysis confirmed that LV mass index and relative wall thickness, in addition to age and systolic blood pressure, were independent predictors for asymptomatic cerebrovascular damage, even in the absence of neurologic abnormalities. In hypertensive patients, LV hypertrophy, and especially concentric LV hypertrophy, provides important prognostic information on the presence of preclinical brain damage. (C)1999 by Excerpta Medica, Inc.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

To elucidate the relationship between postprandial hypotension (PPH) and asymptomatic cerebrovascular damage, we evaluated changes in blood pressure after a meal by 24-hour blood pressure monitoring in 70 hospitalized essential hypertensive patients aged greater than or equal to 50 years. They received a diet containing standard nutritional ingredients with 120 mmol (7 g) NaCl and were free from medication for at least 1 week. PPH was defined as the mean reduction of systolic blood pressure during 2 hours after a meal. Patients were divided into three groups according to mean values of PPH after 3 meals: PPH-1 (n=16, 5 mm Hg less than or equal to PPH&lt;10 mm Hg), PPH-2 (n=18, PPH greater than or equal to 10 mm Hg), and normal (n=36, PPH&lt;5 mm Hg). As asymptomatic cerebrovascular damage, lacunae and leukoaraiosis were evaluated by magnetic resonance imaging. PPH did not correlate with daytime or nighttime blood pressure or the nondipper phenomenon; however, PPH was significantly related to asymptomatic cerebrovascular damage. The prevalence of lacunae in the normal, PPH-1, and PPH-2 groups was 44%, 69%, and 83%, respectively (chi(2)=8.22, P&lt;0.05). The number of lacunae in the normal, PPH-1, and PPH-2 groups was 1.0+/-1.3, 1.3+/-1.2, and 1.9+/-1.4, respectively (F[2,67]=3.2, P&lt;0.05). The prevalence of advanced leukoaraiosis in the normal, PPH-1, and PPH-2 groups was 44%, 50%, and 83%, respectively (chi(2)=7.63, P&lt;0.05). Severity score of leukoaraiosis in the normal, PPH-1, and PPH-2 groups was 1.5+/-0.7, 1.7+/-0.8, and 2.1+/-0.7, respectively (F[2,67]=4.3, P&lt;0.05). These findings indicate that elderly hypertensive patients with marked PPH should be considered to have advanced cerebrovascular damage even in the absence of abnormal neurological findings.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective To understand the regulatory mechanism of platelet-derived growth factor beta-receptor gene expression.
Methods A 1.7 kb genomic fragment was obtained from a rat genomic library. After we had determined an entire sequence of this fragment, transcription start sites were determined both by primer extension analysis and by riboprobe mapping. We performed a functional promoter assay by using a dual-luciferase reporter system. Progressive 5'-deletions of the fragment and site-directed mutagenesis for the CCAAT motif located at -67 or -94 were used for the assay, and their promoter activities in vascular smooth muscle cells were assessed. Gel-mobility shift analysis was also performed for the CCAAT motif at -67. Effects of the upstream sequence spanning -310 through -120 on heterologous gene promoters were also investigated.
Results Multiple transcription start sites were observed in the 5'-flanking region, and the 1.7 kb sequence was actually active as a functional promoter in vascular smooth muscle cells. Two important sequences responsible for the basal transcriptonal activity were identified by the functional promoter assay. One was the CCAAT motif at -67 which acts as a promoter itself, and the other was the upstream region spanning -310 through -210 which positively regulates the basal promoter activity.
Conclusion The basal promoter activity of the rat platelet-derived growth factor beta-receptor gene is mainly regulated by the interaction or coordination of two sequences, the CCAAT motif and the upstream control element. (C) 1998 Lippincott Raven Publishers.

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Geriatrics Society  

A 71-year-old woman was admitted to hospital because of malaise and blood stool. Laboratory findings consistently showed anemia (Hb 9.2g/dl) and occult blood in the stool. Although barium series and endoscopy of the upper and lower intestinal tructs were carried out, there was no evidence of bleeding from the gastrointestinal tract. 99mTcO4/- scintigraphy, which was performed to exclude bleeding from Meckel's diverticulum, also did not locate a significant lesion. Angiographic imaging of the superior mesenteric arteries (SMA) was performed to exclude lesions such as small intestine tumors with extraluminal growth and vascular abnormalities such as A-V malformation and it revealed the round encasement of arteries in the peripheral SMA region, strongly suggestive of a small intestine tumor. Surgery was performed and an extraluminally protruding tumor was found in the small intestine. The excised tumor was 4 x 3 x 3.5 cm in size, are was diagnosed histologically as aberrant pancreas. The postoperative laboratory findings showed that the anemia had improved and occult blood was not detected in the stools. Although aberrant pancreas of the small intestine is a common benign tumor, it is a very unusual cause of bleeding from the alimentary tract.

DOI： 10.3143/geriatrics.35.53

Scopus

PubMed

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Language：Japanese   Publisher：The Japan Geriatrics Society  

A 70-year-old man was admitted to our hospital for further evaluation of recurrent fever, which had begun in October 1994. The patient had 5 to 7 days without fever, and then 2 to 3 days of fever. He had headaches during the febrile periods. On admission, he had abnormal pyramidal, extrapyramidal, and celebellar signs, and nuchal rigidity during the febrile period. However, these neurological abnormalities were completely absent during the afebrile period. Examination of cerebrospinal fluid revealed pleocytosis of mononuclear cells. During the febrile period, pleocytosis was associated with high levels of IgG, IL-6, TNF-α, and PGE₂ in the cerbrospinal fluid. Administration of indomethacin prevented the fever, which suggests that abnormal production of cytokines in the cerebrospinal fluid contributes to fever in Mollaret meningitis.

DOI： 10.3143/geriatrics.34.65

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Geriatrics Society  

A 90-year-old man fell into a marsh and was rescued 18 hours later. When he was admitted to our emergency room, physical examination revealed no remarkable findings except for many abrasions on his skin. Laboratory examination reveled a serum CPK level of 46, 904 IU/L, which had further increased to 84,678 IU/L by the following day. Oliguria developed on the second day, along with an increase in serum creatinine to 5.5 mg. dl. Hemodialysis was considered for the treatment of acute renal failure, but his renal function recovered soon by the continuation of conservative fluid therapy. Fluid therapy may be an effective and easy treatment for acute renal failure due to the crush syndrome, even in very old patients.

DOI： 10.3143/geriatrics.33.783

Scopus

PubMed

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本認知症学会  

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Language：Japanese   Publisher：ライフサイエンス出版(株)  

試験飴は、砂糖、水飴、香料に1粒あたりクロモジエキスを配合し作製した。プラセボ飴は試験飴からクロモジエキスを除き、カラメルを配合し試験飴と同色に着色したものとした。インフルエンザの予防接種を受けた看護スタッフ135名を対象とし、無作為に試験飴摂取群67名(男性3名、平均37.9±11.9歳)、プラセボ飴摂取群67名(男性6名、平均37.4±10.0歳)に割り付けた。試験食品が起因する有害事象は認めなかった。インフルエンザ罹患者数は試験飴摂取群2名(3.0%)、プラセボ飴摂取群9名(13.4%)で、2群間に有意差を認めた。試験飴摂取群で罹患した2名はいずれもインフルエンザB型で、プラセボ飴摂取群では9名中A型が6名、B型は3名であった。罹患患者のうち複数回インフルエンザに罹患した者はなく、欠勤期間は試験飴摂取群4〜5日、プラセボ飴摂取群2〜6日で違いはみられなかった。インフルエンザに起因しない風邪症状においては、発熱、のど、鼻に症状が1回以上みられた人数、発症期間、発熱の有無、のど症状の有無、鼻症状の有無についてはいずれも群間に差は認めなかった。

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J01471&link_issn=&doc_id=20180906210013&doc_link_id=issn%3D0386-3603%26volume%3D46%26issue%3D8%26spage%3D1369&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0386-3603%26volume%3D46%26issue%3D8%26spage%3D1369&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Language：Japanese   Publisher：(一社)日本老年医学会  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本老年医学会  

DOI： 10.3143/geriatrics.55.158

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：English   Publisher：Nature Publishing Group  

大腿筋量と足関節-上腕血圧指数(ABI)との関連性を評価するため、二つの独立した地域における健康推進の包括的コホートを用いて横断研究を行った。日本しまなみ健康推進プログラム(J-SHIPP)研究の抗加齢研究コホート(AASC)に参加した1765例(男性707例、女性1058例、男性平均年齢65.7±9.9歳、女性平均年齢65.1±9.0歳)と長浜研究コホートに参加した8039例(男性2557例、女性5482例、男性平均年齢60.5±13.2歳、女性平均年齢57.4±12.7歳)を対象とした。AASCコホートにおける散布図を用いた評価では、大腿筋断面積(CSA)とABIとの間に有意な正の相関がみられた。この正の相関は長浜コホートにおいても再現された。被験者をABIおよび骨格筋量指標(SMI)の第三四分位数で細分化し(ABI:男性1.16以上、女性1.14以上、SMI:男性8.14以上、女性6.56以上)、多重ロジスティック回帰分析を行ったところ、正常筋量の被験者ではインスリン抵抗性が高ABIの独立決定因子として同定されたが、高筋量の被験者ではそれらのパラメータ間に負の関連がみられた。以上より、大腿筋量はABIの強力な決定因子であることが示唆された。

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本認知症学会  

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Language：Japanese   Publisher：(一社)日本抗加齢医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

J-GLOBAL

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：KARGER  

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J-GLOBAL

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Language：Japanese   Publisher：(株)メディカルレビュー社  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER IRELAND LTD  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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