Hiroshi Shimokata

Association of polymorphisms in the estrogen receptor α gene with body fat distribution

OBJECTIVE: To examine whether polymorphisms of the estrogen receptor (ER) α gene are associated with body fat distribution.DESIGN: Cross-sectional, epidemiological study of two single-nucleotide polymorphisms, a T → C (PvuII) and an A → G (XbaI), in the first intron of the ERα gene.SUBJECTS: A total of 2238 community-dwelling middle-aged and elderly Japanese population (age: 40–79 y).MEASUREMENTS: The ERα genotypes (by automated fluorescent allele-specific DNA primer assay system), anthropometric variables, fat mass (FM) and percentage FM (%FM) (by dual-energy X-ray absorptiometry).RESULTS: FM and waist were inversely associated with age (r=−0.630 and −0.504, respectively) in women with the GG genotype. On the other hand, waist circumference of the AA genotype was positively correlated with age (r=0.231). Thus, for middle-aged women (40–59 y) with the AG or GG genotype body mass index (BMI), %FM, FM, waist, hip and waist-to-hip ratio (WHR) were larger than those with the AA genotype. In particular, FM and waist were greater by 20% and 9%, respectively, for the GG genotype, compared to the AA genotype. Alternatively, FM and waist were smaller by 18% and 6%, respectively, in older women with the GG genotype, compared to the AA genotype. No effect was found among the A → G polymorphisms for men. For both genders, no difference was found in any variables among the TT, TC and CC genotypes with the exception of BMI of older men (60–79 y).CONCLUSION: No association was found between the ERα gene polymorphisms and body fat distribution in men. For women, the A → G polymorphism, in particular the GG genotype, may contribute to the development of upper-body obesity in middle-aged individuals, but may serve to decrease the whole-body and abdominal fat tissue of older individuals.

Refractive errors and factors associated with myopia in an adult Japanese population.

PURPOSE To investigate the refractive status and factors associated with myopia by a population-based survey of Japanese adults. METHODS A total of 2168 subjects aged 40 to 79 years, randomly selected from a local community, were assessed in a cross-sectional study. The spherical equivalent of the refractive error was calculated and used in a multiple logistic regression analysis to evaluate the relationships between myopia and possible related factors. RESULTS The mean (+/- SD) of the spherical equivalent was -0.70 +/- 1.40 diopters (D) in men, and -0.50 +/- 1.44 D in women. Based on +/- 0.5 D cutoff points, the prevalence of myopia, emmetropia, and hypermetropia were 45.7%, 40.8%, and 13.5% in men, and 38.3%, 43.1%, and 18.6% in women, respectively. A 10-year increase in age was associated with reduced risk of myopia [men: odds ratio (OR) = 0.53, 95% confidence interval (CI): 0.44-0.62; women: OR = 0.65, 95% CI: 0.54-0.78]. In men, myopia was significantly associated with higher education (high school: OR = 1.6, 95% CI: 1.1-2.3; college: OR = 2.0, 95% CI: 1.3-3.1) and management occupations (OR = 1.6, 95% CI: 1.0-2.4). For women, high income (OR = 1.5, 95% CI: 1.1-2.2), and clerical (OR = 1.5, 95% CI: 1.0-2.4) and sales/service occupations (OR = 1.7, 95% CI: 1.1-2.6) were also associated with myopia. CONCLUSIONS The prevalence of myopia in a Japanese population was similar to that in other Asian surveys but higher than in black or white populations. Our study confirmed a higher prevalence of myopia among younger vs. older populations, and a significant association with education levels and socioeconomic factors.

A randomized controlled trial of multicomponent exercise in older adults with mild cognitive impairment.

Background To examine the effect of multicomponent exercise program on memory function in older adults with mild cognitive impairment (MCI), and identify biomarkers associated with improvement of cognitive functions. Methodology/Principal Findings Subjects were 100 older adults (mean age, 75 years) with MCI. The subjects were classified to an amnestic MCI group (n = 50) with neuroimaging measures, and other MCI group (n = 50) before the randomization. Subjects in each group were randomized to either a multicomponent exercise or an education control group using a ratio of 1∶1. The exercise group exercised for 90 min/d, 2 d/wk, 40 times for 6 months. The exercise program was conducted under multitask conditions to stimulate attention and memory. The control group attended two education classes. A repeated-measures ANOVA revealed that no group × time interactions on the cognitive tests and brain atrophy in MCI patients. A sub-analysis of amnestic MCI patients for group × time interactions revealed that the exercise group exhibited significantly better Mini-Mental State Examination (p = .04) and logical memory scores (p = .04), and reducing whole brain cortical atrophy (p<.05) compared to the control group. Low total cholesterol levels before the intervention were associated with an improvement of logical memory scores (p<.05), and a higher level of brain-derived neurotrophic factor was significantly related to improved ADAS-cog scores (p<.05). Conclusions/Significance The results suggested that an exercise intervention is beneficial for improving logical memory and maintaining general cognitive function and reducing whole brain cortical atrophy in older adults with amnestic MCI. Low total cholesterol and higher brain-derived neurotrophic factor may predict improvement of cognitive functions in older adults with MCI. Further studies are required to determine the positive effects of exercise on cognitive function in older adults with MCI. Trial Registration UMIN-CTR UMIN000003662 ctr.cgi?function = brows&action = brows&type = summary&recptno = R000004436&language = J.

The relationship between age and intraocular pressure in a Japanese population: The influence of central corneal thickness

Purpose. Previous cross-sectional Japanese studies have shown that intraocular pressure (IOP) decreases with age. However, central corneal thickness (CCT) variation should also be considered when examining the relationship between age and IOP, since tonometry has an inherent measurement error due to CCT variations. This study investigates the influence of CCT variation on the age-IOP relationship in a Japanese population. Methods. The right eyes of 1317 subjects from 40 to 80 years old selected from a general population using a random sampling method were assessed in cross-section. The IOP was measured with a non-contact tonometer, and CCT was measured with a specular microscope. The relationships between age, IOP, and CCT were assessed using correlation analyses, while the relationship between age and IOP controlled for CCT, blood pressure, and body mass index was investigated using multivariate regression analyses. Results. The mean (± SD) IOP value was 13.6 (± 2.6) mmHg in men and 13.3 (± 2.6) mmHg in women. The IOP correlated inversely with age in men (r = -0.14, p <0.001), but showed only a marginal inverse correlation in women (r = -0.07, p = 0.066). The mean (± SD) CCT value was 518.3 (± 33.2) µm in men and 511.1 (± 33.0) µm in women. Only in men was an inverse correlation seen between CCT and age (r = -0.10, p = 0.009), but both genders had positive correlations between CCT and IOP (man: r = 0.44, p < 0.001; woman: r = 0.48, p < 0.001). In multivariate analyses, CCT was shown to have an effect on IOP measurement, however, it was shown that IOP still decreases with age in both sexes even when adjusted for CCT (p = 0.001). Conclusions. The IOP decreases with age in the Japanese, and CCT variation has practically no effect on the unique age-IOP relationship.

Age Differences in the Effect of Physical Activity on Depressive Symptoms

This study examined associations between physical activity and depressive symptoms in 1,151 community-dwelling adults in Japan. Physical activity was measured using a pedometer, whereas depressive symptoms were assessed with the Center for Epidemiological Studies-Depression Scale. A structural equation modeling with a cross-lagged panel design revealed that for the older adults (65-79 years of age), daily walking at baseline predicted fewer depressive symptoms at the 2-year follow-up, even after adjusting for confounders. In contrast, the association was not confirmed for the middle-aged adults (40-64 years of age). Findings suggest that age should be considered when estimating the effect of physical activity on psychological well-being.

The Clock Drawing Test as a Valid Screening Method for Mild Cognitive Impairment

To validate the Clock Drawing Test (CDT) as a screening method for detecting mild cognitive impairment (MCI) and to find the appropriate scoring protocol and its cutoff point, we compared the sensitivity and specificity of three CDT protocols. Subjects included 219 outpatients with memory complaints, who were attending the geriatric memory clinic. Cahn’s protocol, with a cutoff point of 7, was more successful at differentiating clinically diagnosed MCI subjects from normal elderly individuals, with higher sensitivity (74.7%) and specificity (75.6%), than were the other protocols. The CDT, as a handy screening method, may be useful for clinicians to reliably identify subjects with MCI, and it may contribute to early detection of dementia.

Mitochondrial ALDH2 Deficiency as an Oxidative Stress

Abstract: Mitochondrial aldehyde dehydrogenase 2 (ALDH2) plays a major role in ethanol metabolism. It is involved in acetaldehyde detoxification. A polymorphism of the ALDH2 gene is specific to North‐East Asians. Sensitivity to ethanol is highly associated with this polymorphism (ALDH2*2 allele), which is responsible for a deficiency of ALDH2 activity. We first show that this deficiency influences the risk for late‐onset Alzheimers disease (LOAD) by a case‐control study in a Japanese population. In a comparison of 447 patients with sex, age, and region‐matched non‐demented controls, the genotype frequency for the ALDH2*2 allele was significantly higher in the patients than in the controls (P=0.001). Next, we examined the combined effect of the ALDH2*2 and the apolipoprotein E4 allele (APOE‐ε4), which has been confirmed to be a risk factor for LOAD. The ALDH2*2 allele more significantly affected frequency and age at onset in patients with APOE‐ε4 than in those without it. These results indicate that the ALDH2 deficiency is a risk factor for LOAD, acting synergistically with the APOE‐ε allele. Next, to elucidate the molecular mechanism involved, we obtained ALDH2‐deficient cell lines by introducing mouse mutant ALDH2 cDNA into PC12 cells. We speculate that ALDH2 may act to oxidize toxic aldehyde derivatives. Then, we found that the ALDH2‐deficient transfectants were highly vulnerable to exogenous 4‐hydroxy‐2‐nonenal, an aldehyde derivative generated from peroxidized fatty acids. In addition, the ALDH2‐deficient transfectants were sensitive to oxidative insult induced by antimycin A, accompanied by an accumulation of proteins modified with 4‐hydroxy‐2‐nonenal. Mitochondrial ALDH2 functions as a protector against oxidative stress.

Dietary patterns of antioxidant vitamin and carotenoid intake associated with bone mineral density: findings from post-menopausal Japanese female subjects

SummaryRecent studies show that antioxidants may reduce the risk of osteoporosis. This study showed the associations of bone mineral density with dietary patterns of antioxidant vitamins and carotenoids. The findings suggest the combination of vitamin C and β-cryptoxanthin intakes might provide benefit to bone health in post-menopausal Japanese female subjects.IntroductionRecent epidemiological studies show antioxidants may reduce the risk of osteoporosis, but little is known about the dietary patterns of antioxidant vitamin and carotenoid intakes and their relation with bone mineral density (BMD).MethodsA total of 293 post-menopausal female subjects who had received health examinations in the town of Mikkabi, Shizuoka Prefecture, Japan, participated in the study. Radial BMD was measured using dual-energy X-ray absorptiometry. Dietary intakes of antioxidant vitamins and carotenoids were assessed by using a validated food-frequency questionnaire. Dietary patterns were identified on a selected set of antioxidants through principal component factor analysis.ResultsThree dietary patterns were identified. The “retinol” pattern, characterized by notably high intakes of preformed retinol, zeaxanthin, and vitamin E, was positively associated with the risk for low BMD. In contrast, the “β-cryptoxanthin” pattern, characterized by notably high intakes of β-cryptoxanthin and vitamin C, was negatively associated with low BMD. The odds ratios for low BMD in the highest tertiles of dietary intakes of preformed retinol, vitamin C, and β-cryptoxanthin against the lowest tertiles were 3.22 [95% confidence interval (CI), 1.38–7.51], 0.25 (CI, 0.10–0.66), and 0.40 (CI, 0.17–0.92), respectively, after adjustments for confounders. However, negative associations of vitamin C and β-cryptoxanthin with low BMD were not significant after further adjustment for intake of β-cryptoxanthin or vitamin C, respectively. Higher intakes of both vitamin C and β-cryptoxanthin were significantly associated with low BMD (P < 0.05).ConclusionsThe combination of vitamin C and β-cryptoxanthin may be associated with radial BMD in post-menopausal Japanese female subjects.

High prevalence of sarcopenia and reduced leg muscle mass in Japanese patients immediately after a hip fracture.

Aim:  Sarcopenia‐related falls and fractures are becoming an emerging problem as a result of rapid aging worldwide. We aimed to investigate the prevalence of sarcopenia by estimating the muscle mass of the arms and legs of patients with and without hip fracture.

Gene structure of human cholecystokinin (CCK) type-A receptor: body fat content is related to CCK type-A receptor gene promoter polymorphism

The transcriptional start site of the human cholecystokinin (CCK)‐A receptor gene was determined by the Capsite Hunting method. Two sequence changes were detected, a G to T change in nucleotide −128, and an A to G change in nucleotide −81. The homozygote (T/T, G/G) was detected in 25 of 1296 individuals (1.9%) in the cohort study. This polymorphism showed a significantly higher percent body fat and higher levels of serum insulin and leptin, compared with wild type and heterozygotes. Our study provided the possibility that polymorphism in the promoter region of the CCK‐A receptor gene may be one of genetic factors affecting fat deposition.