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

（Objective）It is possible to hypothesize that if the graduation rate within 6 years of medical students is decreased, the pass rate of National examination is increased. But it is unknown that this hypothesis is true or not. <br />
(Method) Based on the data of National and public medical schools in 2016-2019, we investigated the correlation between a pass rate of National examination for medical practitioners and a graduation rate for six years. <br />
(Result) There is no or little relation between the factors used.<br />
(Conclusion) For increasing the pass rate, we have to search other methods to enhance students’ learning performance.

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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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© 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley &amp; Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders 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：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：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：Japanese   Publisher：愛媛医学会  

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Masked hypertension (HT) is a known risk factor for cardiovascular outcomes. Postural blood pressure (BP) dysregulation is another BP phenomenon representing cardiovascular frailty. Given their several shared risk factors, we suspected an interrelationship between these two BP phenomena. Here we investigated a possible relationship between masked HT and postural BP dysregulation in a general population. Study subjects were 884 apparently healthy individuals (aged 66.3 +/- 8.9 years). Masked HT was assessed on the basis of the ambulatory monitored average awake BP and office-measured BP values. Orthostatic BP change was measured at our office after a subject was asked to actively stand up. A strong inverse relationship was noted for orthostatic systolic BP (SBP) change and office-to-awake SBP differences (office-awake BP) (r=-0.422, P&lt;0.001), and these relationships were replicated in the second-visit measurements (n=101, r=-0.326, P=0.001). Multivariate analysis revealed that the inverse association was independent (beta=-0.23, P&lt;0.001) of possible covariates, including baseline office BP and antihypertensive treatment. Orthostatic HT (OHT), which is defined as postural increases in SBP &gt; 10 mm Hg, 3 min after standing (P=0.001), but not transient HT at only 1 min (P=0.767), was associated with greater office-to-awake SBP differences than in orthostatic normotensive subjects. Among apparently normotensive subjects, the frequency of masked HT was therefore significantly greater in subjects who showed OHT 3 min after standing (52.1%) compared with controls (27.5%) (odds ratio = 3.01, P=0.001). We observed an intra-individual relationship between the postural BP change and the office-to-awake BP differences, and subjects who showed OHT were likely to have masked HT irrespective of antihypertensive treatment.

DOI： 10.1038/hr.2016.43

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

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 &lt; .0001] and that of SF score 2 was 3.3 [2.1-5.3, p &lt; .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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ijcard.2016.04.135

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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: beta = 0.069, P = 0.002; d/a: beta = -0.009, P = 0.669; and aging index: beta = 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：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：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1212/WNL.0000000000001797

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

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 &lt;20 s, increased linearly with severity of cSVD (lacunar infarction lesion: none, 9.7%; 1, 16.0%; &gt;2, 34.5%; microbleeds lesion: none, 10.1%; 1, 15.3%; &gt;2, 30.0%; periventricular hyperintensity grade: 0, 5.7%; 1, 11.5%; &gt;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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DOI： 10.3995/jstroke.37.36

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

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&lt;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&lt;0.0001) and lower SS (P&lt;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 &gt;3. Regression lines between blood pressure and WT were significantly steeper in subjects with SVD than without SVD (=0.02; P&lt;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：Japanese   Publisher：(NPO)日本高血圧学会  

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

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 crass-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 &lt;0.0001) and thigh muscle CSA (r = -0.25, p &lt;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 (beta = 0.27, p &lt;0.0001). These findings indicate that along with. adiposity, muscle mass is an independent determinant of plasma BNP. (C) 2014 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.amjcard.2014.05.050

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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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.atherosclerosis.2014.05.940

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Language：English   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.ijcard.2014.03.194

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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)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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 &lt; 0.001) and had higher preprandial BP (P &lt; 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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DOI： 10.1111/j.1468-1331.2012.03879.x

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

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 &lt; 0.001) and insulin resistance (1.0 +/- 0.6, 1.2 +/- 0.7, 1.3 +/- 0.8, 1.5 +/- 1.0, p &lt; 0.001). Multiple linear regression analysis adjusted for possible covariates identified hematocrit as an independent determinant of insulin sensitivity (beta = -0.074, p = 0.019) and insulin resistance (beta = 0.115, p &lt; 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 &lt; 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   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective: Several large-scale studies have shed light on the primary preventive efficacy of statins against atherosclerotic diseases in the course of treatment of dyslipidemia. However, this efficacy in the management of dyslipidemia in relatively low-risk patients, particularly in women, has not been clarified. Here, we investigated the efficacy of dyslipidemia treatment with a statin on three indices that are widely used to assess atherosclerosis in postmenopausal women: carotid intima-media thickness (CIMT), arterial stiffness index beta of the common carotid artery (carotid stiffness beta), and brachial artery pulse wave velocity (baPWV).
Methods: The study enrolled 51 postmenopausal women aged 55 years or older with dyslipidemia. The participants were randomly divided into two treatment groups and received a single daily administration of 2.5 mg of rosuvastatin or no statin therapy as control.
Results: At baseline, the groups did not significantly differ with regard to the three indices. At the third and 12th months of treatment, both carotid stiffness beta and baPWV values were significantly lower than those of the control group. As for CIMT, the value was significantly lower in the statin group than in the control group at 12 months of treatment. These changes were in conjunction with a significant decrease in low-density lipoprotein cholesterol. Interestingly, changes in CIMT during the 12-month period were significantly correlated with changes in high-sensitivity C-reactive protein during the 3-month period independently of lipid profile.
Conclusions: The potent statin improves baPWV and carotid stiffness beta, in addition to CIMT (surrogate markers of coronary artery disease), in postmenopausal women with low-risk dyslipidemia. Further studies to clarify the common mechanisms underlying the link between cholesterol-lowering therapy and atherosclerosis in postmenopausal women are required.

DOI： 10.1097/gme.0b013e318259c04e

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Language：English   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.ijcard.2012.04.033

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

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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 hy-poreflexia and hypoesthesia, but with a bilateral pyramidal tract sign. A study of her cerebrospinal fluid revealed albumino-cytologic dissociation, and nerve conduction study revealed demyelination of her peripheral nerves. Moreover, electroen-cephalography 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. © 2012, The Japan Geriatrics Society. All rights reserved.

DOI： 10.3143/geriatrics.49.367

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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：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

The combination of sarcopenia, age-related loss of muscle strength and mass, and obesity has been recognized as a new category of obesity among the elderly. Given that leptin has been hypothesized to be involved in the pathogenesis of sarcopenic obesity, we investigated the relationship between plasma leptin levels and thigh muscle sarcopenia and visceral obesity. Thigh muscle cross-sectional area (CSA) and visceral fat area were measured using computed tomography as indices for muscle mass and visceral fat, respectively, in 782 middle-aged to elderly subjects (303 men and 479 women), participating in a medical check-up program. Visceral obesity was defined as visceral fat area &gt; 100 cm(2), and sarcopenia was defined as &lt; (one standard deviation - mean of thigh muscle CSA/body weight of young subjects [aged &lt;50 years]). Thigh muscle CSA was significantly and negatively associated with plasma levels of leptin in both men (beta = -0.28, p&lt;0.0001) and women (beta = -0.20, p&lt;0.0001), even after correcting for other confounding parameters, including age, body weight, body height, visceral fat area, blood pressure, homeostatic model assessment index, and high sensitive C reactive protein. Subjects were divided into four groups based on presence or absence of sarcopenia or visceral obesity. Plasma levels of leptin were higher in subjects with sarcopenic visceral obesity than in those with either sarcopenia or visceral obesity alone. These findings indicate that sarcopenic visceral obesity is a more advanced, and suggest that leptin may link visceral obesity and sarcopenia.

DOI： 10.1371/journal.pone.0024633

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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)   Publisher：NATURE PUBLISHING GROUP  

BACKGROUND
Recent studies have reported the association between advanced arterial stiffness and brain small vessel diseases (SVDs). two possible hemodynamic mechanisms, increases in central blood pressure (BP) and pulsatile flow load to the brain, have been speculated to link arterial stiffness and SVD. the carotid flow augmentation index (AI) has been proposed as an index of pulsatile flow to the brain. We compared its association with brain SVD with that of central BP in a general population.
METHODS
Subjects were 500 individuals free from symptomatic cardiovascular diseases with a mean age of 66.9 +/- 8.4 years. Brachial-ankle pulse wave velocity (baPWV) was measured as an index of arterial stiffness. Carotid flow AI was obtained by Doppler ultrasonography. the presence of silent cerebral lacunar infarcts (SCI) was determined as a manifestation of SVD by 3-tesla magnetic resonance imaging (MRI). second peak radial systolic BP (SBP2) and pulse pressure (PP2) were used as estimates of central BP.
RESULTS
baPWV was significantly associated with radial BP2 (r = 0.55, P &lt; 0.0001) but not with carotid flow AI (r = 0.03, P = 0.51). Radial BPs and baPWV, but not flow AI, were significantly higher in subjects with SCI. Radial SBP2 had higher odds ratio for the presence of sCI than brachial SBP, PP, and radial PP2. Logistic regression analysis showed that radial SBP2, but not flow AI, was independently related to the presence of sCI.
CONCLUSION
These findings indicate that the SBP2, an estimate of central SBP, is significantly associated with the presence of SVD in an apparently healthy general population.

DOI： 10.1038/ajh.2010.60

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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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A 72-year-old woman was admitted to a local hospital with general fatigue, ptosis and dysarthria. Her anti-AchR antibody titer was high, so myasthenia gravis was diagnosed. She was given a cholinesterase inhibitor, but her symptoms did not improve. CT and MRI scans revealed a mass in the anterior mediastinum infiltrating the superior vena cava (SVC) and the right atrium (RA). The diagnosis was an invasive thymoma extending into the SVC and the RA. Moreover, there was a mass in the right middle lobe of her lung, which was suspected to be the result of metastasis of the thymoma. She was transferred to our hospital for medication and surgery for the invasive thymoma. Urgent surgery was performed without preoperative therapy, because the tumor was nearly obstructing her tricuspid valve. An expanded thymomectomy and a right middle lobectomy were performed. As the tumor had infiltrated into the SVC, the SVC was replaced with an artificial graft. The clinicopathological diagnosis of thymoma (Masaoka Stage IVb) was given. The patient had a myasthenic crisis for several weeks after surgery, so her breathing was controlled by an artificial respirator. Her symptoms improved after treatment with steroids, tacrolimus and a cholinesterase inhibitor. Although major surgery was required to prevent tumor embolism, the patient survived. Careful observation is necessary to detect signs of relapse of invasive thymoma.

DOI： 10.3143/geriatrics.47.158

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Background/Aims: Mobility impairment in older adults has been suggested to be a marker of subclinical structural and functional brain abnormalities. We investigated a possible association between static postural instability and brain abnormalities and cognitive decline. Methods: The study subjects were 390 community residents without definitive dementia (67 +/- 7 years old) and 21 patients with Alzheimer's disease (AD). Brain atrophy was measured by MRI. Results: The mobility of the posturography-measured center of gravity (COG) was positively associated with the temporal horn area (THA; r = 0.260; p &lt; 0.001). Subjects who could not stand on one leg for &gt;40 s (n = 102) showed a significantly larger THA (22 +/- 18 vs. 14 +/- 11 x 10(-2) cm(2); p &lt; 0.001). Multiple regression analysis identified COG path length (beta = 0.118; p = 0.032) and one-leg standing time (beta = 0.176; p = 0.001) as independent determinants of THA. Mild cognitive impairment (MCI) subjects (n = 61) had a significantly enlarged THA compared to that of normal cognitive subjects (22 8 16 vs. 16 +/- 13 x 10-(2) cm(2); p = 0.002). AD patients showed a more enlarged THA (78 +/- 55 x 10(-2) cm(2)). Subjects with cognitive decline showed a significantly shorter one-leg standing time (normal: 50 +/- 17 s; MCI: 42 +/- 21 s; AD: 18 +/- 20s; p &lt; 0.001). Conclusion: Reduced postural stability was an independent marker of brain atrophy and pathological cognitive decline in the elderly. Copyright (C) 2010 S. Karger AG, Basel

DOI： 10.1159/000255106

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Background/Aim: Lower body weight in later life has been shown to be associated with dementia. However, abdominal fat distribution under conditions of mild cognitive impairment (MCI) and the possible involvement of leptin and adiponectin in MCI have not been fully investigated. Methods: We analyzed 517 middle-aged-to-elderly community-dwelling persons. Abdominal subcutaneous fat and visceral fat areas were determined using computed tomography, and plasma leptin and adiponectin concentrations were measured in fasting samples. MCI was assessed using the Japanese version of the MCI screening method. Results: In men, the abdominal subcutaneous fat area was significantly lower in participants with MCI than in those with normal cognitive function [median (interquartile range): 107.4 (85.9, 133.1) cm(2) vs. 136.4 (93.1, 161.4) cm(2); p = 0.002]. Logistic regression analyses with confounding factors including age and abdominal subcutaneous fat area showed that a 10 mg/l increase in plasma adiponectin had a protective effect against the development of MCI in men (odds ratio: 0.46; 95% CI: 0.20-0.97; p = 0.041). In contrast, MCI was not found to be associated with abdominal fat area or adipose-derived hormones in women. Conclusion: Reduced amounts of subcutaneous fat and low levels of plasma adiponectin were found to be associated with MCI in men. Copyright (C) 2010 S. Karger AG, Basel

DOI： 10.1159/000321985

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

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DOI： 10.1038/jhh.2008.154

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DOI： 10.1016/j.jjcc.2009.04.001

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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)   Publisher：JAPANESE CIRCULATION SOC  

Background. Cerebral microbleed (CMB), which is conspicuous on gradient-echo T2*-weighted magnetic resonance imaging, is a risk factor of intracerebral hemorrhage (ICH). CMBs have been detected even in neurologically healthy persons, who also seem prone to be affected by stroke, not only ICH but also cerebral infarction.
Methods and Results: The presence of CMB was investigated in brain dock participants, making reference to silent lacunar infarction (SLI). Participants comprised 377 neurologically healthy persons and 21 (5.6%) had CMB detected, which was associated with a high incidence of hypertension, other conventional risk factors having no significant correlation with CMB. In a simple correlation analysis, CMB showed a positive association with age and systolic blood pressure (SBP). Logistic regression analysis revealed that SLI was the factor most strongly associated with CMB. Moreover, individuals who had both CMB and SLI had higher SBP than other groups.
Conclusions: The etiology of CMB is similar to that of SLI. (Circ J 2009; 73: 530-533)

DOI： 10.1253/circj.CJ-08-0764

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Silent cerebral microbleeds (MBs) are a common finding in stroke patients, especially those with intracerebral hemorrhage, and are thought to be a marker of future cerebral hemorrhage. Clinically, two distinct forms of MBs have been documented, those observed with either or both stroke or small vessel disease (SVD) and those associated with cerebral amyloid angiopathy. We investigated a possible association between MBs and arterial stiffness in a general population. Subjects were 443 apparently healthy individuals with a mean age of 67.1±8.1 years. The presence of MBs, lacunar infarcts and periventricular hyperintensity (PVH) was determined by 3-tesla magnetic resonance imaging. Carotid intima-media thickness (IMT) was measured by ultrasonography. Arterial stiffness was evaluated by brachial-to-ankle pulse wave velocity (baPWV), and the Framingham stroke risk score (FSRS) was obtained as an integrated cerebrovascular risk factor. The prevalence of MBs was 5.0%. Both baPWV and FSRS were significantly higher in subjects with MBs (1820±308 vs. 1645325 cm/s, P=0.014 and 12.1±8.6 vs. 8.9±7.5%, P=0.047, respectively). Odds ratio of a high baPWV, defined as ≥1500 cm/s, for the presence of MBs was 6.05 even after correction for confounding parameters, including age and hypertension. This association with high baPWV remained irrespective of MBs location, whether strictly located in the lobes or in the basal ganglia and infratentorial regions. These findings indicate an association between arterial stiffness and the presence of MBs. Assessment of arterial stiffness may be useful in identifying subjects at high risk for the presence of MBs. © 2009 The Japanese Society of Hypertension All rights reserved.

DOI： 10.1038/hr.2009.13

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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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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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Angiotensin converting enzyme 2 (ACE2), a newly recognized homolog of ACE that converts angiotensin II (Ang II) to angiotensin-1-7 (Ang-(1-7)), is found in vascular smooth muscle cells. Expression of ACE2 may be a local determinant of vascular Ang-(1-7) production and, when increased, may augment the increasingly recognized protective effects of this peptide within injured tissues. We previously showed that treatment with the angiotensin II type 1 (AT1) receptor blocker (ARB) olmesartan increased aortic ACE2 and Ang-(17) in conjunction with improved vascular remodeling in spontaneously hypertensive rats (SHR). In the present study, we investigated balloon injury-related ACE2 in the vasculature by determining the effect of sustained AT1 blockade on ACE2 protein expression in the carotid arteries of 12-week-old male SHR treated with either vehicle (n = 5) or 10 mg/kg olmesartan (n = 5) in drinking water for 14 days. Olmesartan treatment caused a 61% reduction in the cross-sectional area of the neointima, from 0.27 +/- 0.01 mm(2) in vehicle-treated rats to 0.11 +/- 0.01 mm(2) in olmesartan-treated rats. In contrast, olmesartan treatment had no effect on the medial area of injured or uninjured carotid arteries compared to that in vehicle-treated rats. Quantitative analysis of ACE2 immunostaining intensity in the carotid artery of SHR was significantly greater (p &lt; 0.05) in the neointima of olmesartan-treated SHR compared to that in vehicle-treated animals. In contrast, ACE2 immunostaining intensity was not quantitatively different in uninjured carotid arteries of olmesartan and vehicle-treated animals. These studies suggest that changes in ACE2 within the vascular system of SHR are regulated by a factor other than arterial pressure.

DOI： 10.1291/hypres.31.553

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

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

Migraine is a common subtype of headache. Epidemiological studies have revealed that migraine could be an independent risk factor for ischemic stroke even in elderly subjects. Arterial stiffness is one of the major path ophysiological bases of stroke. In the present study, we cross-sectionally investigated the possible relationship between migraine and arterial stiffness in community-dwelling subjects. The study subjects were independently recruited from two sources (Group A, n=134, 68 +/- 5 years; Group B, n=138, 68 7 years). Augmentation index (AI), the ratio of augmented pressure by the reflection pressure wave to the pulse pressure, was obtained from the radial arterial waveform as an index of arterial stiffness. Brachial blood pressure was also measured simultaneously. Migraine was diagnosed using a previously validated questionnaire. The prevalence of migraine was 5.2% (Group A) and 16.7% (Group 13). Subjects with migraine had higher radial Al in both Group A (migraine, 101 +/- 15%; other headache, 88 +/- 12%; no headache, 86 +/- 12%, p=0.003) and Group B (95 +/- 11%, 90 +/- 11%, 91 +/- 14%, p=0.058). Multiple linear regression analysis revealed that migraine was an independent determinant of Al (ss=0.154, p=0.002) after adjustment for other confounding factors: age (ss=-0.024, p=0.654); sex (ss=0.141, p=0.069); body height (ss=-0.215, p=0.005); systolic blood pressure (ss=0.174, p=0.001); medication for hypertension, hyperlipidemia, and diabetes mellitus (ss=-0.014, p=0.787); and heart rate (ss=-0.539, p &lt; 0.001). In a separate analysis by sex, migraine was also a significant determinant for Al (male, ss=0.246, p=0.019; female, ss=0.159, p=0.008). Migraine in the elderly could be a clinical manifestation of enhanced arterial stiffness.

DOI： 10.1291/hypres.30.577

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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)   Publisher：JAPANESE SOC HYPERTENSION CENT ACADEMIC SOC, PUBL OFFICE  

Serotonin has been implicated in the pathogenesis of hypertension because of its ability to induce vasoconstriction via stimulation of serotonin 2 (5-HT2) receptors. Recently, an association between the T102C functional polymorphism of the serotonin 2A (5-HT2A) receptor gene and hypertension in the UK has been reported. Another association study, however, failed to replicate this association in a Chinese population. We therefore investigated the possible association between the 5-HT2A T102C polymorphism and hypertension in two large Japanese populations (n = 2,968 total). We also investigated the possible interaction between the 5-HT2A T102C polymorphism and the G/T (Lys198Asn) polymorphism of the endothelin-1 (ET-1) gene, based on robust biological evidence for the existence of an interaction between the serotonin and endothelin systems. The results showed that there was no significant difference in the frequencies of the alleles and genotypes between the hypertensive and normotensive subjects. However, a significant interaction between the 5-HT2A T102C and ET-1 G/T polymorphisms in their association with hypertension (p = 0.0040) and with diastolic blood pressure (p = 0.0013) was revealed. A marginally significant interaction in the association with systolic blood pressure was also shown (p = 0.045). The associations of the 5-HT2A T102C polymorphism with hypertension and diastolic blood pressure in ET-1 T allele carriers were significant (p = 0.0056 and 0.021, respectively). The association of the 5-HT2A T102C polymorphism with systolic blood pressure in ET-1 T allele carriers was marginally significant (p = 0.054). Thus, the present study suggests that the 5-HT2A T102C and ET-1 G/T polymorphisms are interactively associated with hypertension.

DOI： 10.1291/hypres.29.227

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

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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