Eri Uetani

Arterial stiffness is associated with low thigh muscle mass in middle-aged to elderly men.

OBJECTIVE Sarcopenia of legs is an important cause of physical dysfunctions, frailty and dependence. Many predisposing and underlying mechanisms of sarcopenia, including age, sedentary life style, oxidative stress, insulin resistance, and low testosterone levels, are also known to be related to atherosclerosis, which is another leading cause of morbidity and mortality in elderly subjects. In this study, we investigated our hypothesis that sarcopenia and atherosclerosis are associated with each other to facilitate mutual abnormalities. METHODS Study was performed in apparently healthy 496 middle-aged to elderly persons recruited consecutively among the visitors to the medical check-up program, Anti-Aging Doc, in a University hospital, from March 2006 to December 2007. Mid-thigh muscle cross-sectional area (CSA) was measured by computed tomography and corrected by body weight (CSA/BW). Carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) were measured. RESULTS Thigh muscle CSA/BW was significantly and negatively associated with carotid IMT and baPWV in men but not in women. After correction for other confounding parameters, baPWV was an independent risk for the presence of sarcopenia in men (odds ratio of 1 m/s increase of baPWV=1.14, 95% CI=1.01-1.30, p<0.05) in addition to age, body height, low physical activity, free testosterone level. Conversely, thigh muscle CSA/BW was an independent determinant of baPWV (beta=-0.15, p<0.01) in addition to age, blood pressure, triglyceride, and antihypertensive drug use in men. CONCLUSIONS Arterial stiffness is related to thigh muscle volume in men. Sarcopenia and atherosclerosis may share a common pathway and interact with each other to facilitate mutual abnormalities.

Quadriceps sarcopenia and visceral obesity are risk factors for postural instability in the middle-aged to elderly population.

Aim:  Aging shifts body composition to comprising more fat and less muscle. Sarcopenia, particularly in the knee extensors, and obesity, particularly visceral obesity, either alone or in combination, may exacerbate age‐related physical disability. We investigated the association between age‐related quadriceps (Qc) sarcopenia and visceral obesity, as measured by cross‐sectional area (CSA), on postural instability.

Abdominal fat, adipose-derived hormones and mild cognitive impairment: the J-SHIPP study.

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) cm2 vs. 136.4 (93.1, 161.4) cm2; 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.

Association of central systolic blood pressure with intracerebral small vessel disease in Japanese.

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 < 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.

Abnormal nocturnal blood pressure profile is associated with mild cognitive impairment in the elderly: the J-SHIPP study

Mild cognitive impairment (MCI), a syndrome characteristic of the transition phase between normal cognitive function and dementia, has been shown to carry the risk of progression to dementia. Dysregulation of blood pressure (BP) is thought to be an indicator of cerebrovascular damage, including cognitive impairment. Here, we investigated the possible association of circadian BP variation with MCI in community-dwelling persons exhibiting no definitive dementia. Our study enrolled 144 persons (68±7 years). Nocturnal BP profile was defined as dipper, with a 10–19% drop in nocturnal systolic BP; extreme dipper, ⩾20% drop; non-dipper, 0–10% drop; and riser, any increase in nocturnal BP. MCI was assessed using the MCI screen, a cross-validated, staff-administered battery of tests. Subjects with MCI (n=38) were significantly older (74±6, 67±6 years, P<0.001) and had higher frequency of apolipoprotein E ɛ4 allele (36.8, 18.9%, P=0.018). Although the ambulatory measured BP and the percent changes in nocturnal systolic BP (−10±12% and −12±8%, respectively; P=0.291) did not differ between MCI subjects and normal controls, frequency of MCI was significantly higher in the extreme dippers (32.0%), non-dippers (30.0%) and risers (50.0%) than in dippers (13.2%, P=0.018). Multiple logistic regression analysis identified a blunted nocturnal BP decline, non-dipping or increase in nocturnal BP and extreme drop in BP as potent determinants of MCI (odds ratio 3.062, P=0.039), after adjustment for possible confounding factors, including apolipoprotein E ɛ4 genotype. Abnormal nocturnal BP profile was found to be a strong indicator of MCI in otherwise apparently healthy community-dwelling elderly persons.

Postural Instability Is Associated with Brain Atrophy and Cognitive Impairment in the Elderly: The J-SHIPP Study

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 < 0.001). Subjects who could not stand on one leg for >40 s (n = 102) showed a significantly larger THA (22 ± 18 vs. 14 ± 11 × 10–2 cm2; p < 0.001). Multiple regression analysis identified COG path length (β = 0.118; p = 0.032) and one-leg standing time (β = 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 ± 16 vs. 16 ± 13 × 10–2 cm2; p = 0.002). AD patients showed a more enlarged THA (78 ± 55 × 10–2 cm2). Subjects with cognitive decline showed a significantly shorter one-leg standing time (normal: 50 ± 17 s; MCI: 42 ± 21 s; AD: 18 ± 20s; p < 0.001). Conclusion: Reduced postural stability was an independent marker of brain atrophy and pathological cognitive decline in the elderly.

Postprandial hypotension as a risk marker for asymptomatic lacunar infarction.

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.

Association of Postural Instability With Asymptomatic Cerebrovascular Damage and Cognitive Decline The Japan Shimanami Health Promoting Program Study

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 magnetic resonance imaging. 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.

CDH13 genotype-dependent association of high-molecular weight adiponectin with all-cause mortality: the J-SHIPP study.

OBJECTIVE Despite its anti-inflammatory and antiatherogenic effects, adiponectin is potentially associated with adverse clinical outcomes, such as all-cause mortality. As plasma adiponectin levels are strongly influenced by single nucleotide polymorphisms in the gene encoding T-cadherin (CDH13), we conducted a longitudinal study to investigate the possible link between the CDH13 genotype, plasma adiponectin levels, and all-cause mortality. RESEARCH DESIGN AND METHODS This longitudinal study evaluated 2,020 Japanese subjects. Baseline clinical parameters were obtained from subjects’ personal health records as evaluated at annual medical check-ups. Plasma high–molecular weight adiponectin (HMWA) levels were measured by an ELISA assay, and genotyping was performed by a TaqMan probe assay. RESULTS Mean follow-up duration was 6.5 years. Kaplan-Meier analysis showed that HMWA levels were positively associated with mortality (P < 0.001). HMWA levels were associated with older age, lower body weight, lower plasma triglyceride and glucose levels, and higher plasma HDL cholesterol. However, the Cox regression analysis showed that the positive association between HMWA and all-cause mortality was independent of these covariates (hazard ratio [HR] 1.92, P = 0.006). The CDH13 rs4783244 genotype was strongly associated with baseline HMWA levels (per-allele effect size 1.65 μg/mL, P < 0.001). In a separate analysis by the CDH13 genotype, the HR for all-cause mortality was linearly increased with the number of G alleles (P value for HMWA–CDH13 genotype interaction = 0.023). CONCLUSIONS Higher plasma HMWA level was an independent prognostic factor for all-cause mortality in a general population. The CDH13 genotype may be a factor that affects not only the plasma level of HMWA but also the prognostic significance of HMWA.

Association of Chr17q25 with cerebral white matter hyperintensities and cognitive impairment: the J‐SHIPP study

A recent genome‐wide association study has successfully identified several genetic variations in the Chr17q25 locus as susceptible genotypes for white matter hyperintensities. We report the first replication study in subjects of non‐European origin. We also investigated possible associations with other asymptomatic cerebrovascular diseases and cognitive function.