Much lower prevalence and mortality of chronic obstructive pulmonary disease in Japan than in the US despite higher smoking rates: A meta analysis/systematic review.

BACKGROUND: A recent systematic review showed Japan's mortality from chronic obstructive pulmonary disease (COPD) is the lowest among 204 countries, despite notably higher smoking rates in men in Japan than in the US. This study aims to compare (1) trends in smoking rates, (2) trends in COPD mortality, and (3) the spirometry-based COPD prevalence in the general adult population between Japan and the US. METHODS: Age- and sex-specific smoking rates from the 1980s through 2010s and COPD mortality from 1999 through 2019 were obtained from national surveys and official statistics (International Classification of Diseases-10th codes J40-44), respectively. A systematic review and meta-analysis was performed to estimate COPD prevalence in Japan, while the National Health and Nutrition Examination Survey 2007-2012 was used for the US. A fixed ratio of 0.7 of forced expiratory volume in the first second of forced vital capacity was used to define COPD. RESULTS: Over the past four decades, men in Japan consistently had 20-30% higher smoking rates than their US counterparts. From 1999-2019, age-adjusted COPD mortality in men in Japan was only a third of the US, whereas that in women was less than a tenth in 2019. Synthesizing data from 11 studies, involving 89,955 participants, Japan's COPD prevalence was more than 10% lower than in the US in almost all age groups for both sexes. CONCLUSIONS: This study showed markedly lower rates of COPD in Japan than in the US. Investigating factors contributing to the paradoxical observations could lead to advancing COPD risk reduction strategies.

Skeletal muscle adiposity is a novel risk factor for poor cognition in African Caribbean women.

OBJECTIVE: Skeletal muscle adiposity (myosteatosis) is recognized as a major risk factor for cardiometabolic diseases, and it increases with aging. The relationship of myosteatosis with cognitive impairment is unknown. METHODS: The association of calf myosteatosis (measured by computed tomography-derived skeletal muscle density; higher values indicate less myosteatosis) with cognitive function was examined among 626 African Caribbean women who were aged 40 to 84 years, a population highly vulnerable to increased myosteatosis. Cognition was assessed by the Digit Symbol Substitution Test (DSST), a test of information processing speed (higher scores indicate better performance). Linear regression was used to assess the association of muscle density with DSST. RESULTS: Adjusting for age, education, muscle area, BMI, hypertension, diabetes, cardiovascular event history, lifestyle factors, lipid-lowering medication use, and menopausal status, a one-SD lower muscle density was associated with a 1.69-point lower DSST score (p = 0.002). BMI, diabetes, and hypertension interactions were not statistically significant, suggesting that the main association was not moderated by overall obesity or cardiometabolic diseases. CONCLUSIONS: These findings suggest that greater myosteatosis is associated with slower information processing speed, an early indicator of cognitive impairment. Further studies are needed to establish this association in this and other populations using an expanded battery of cognitive tests with longitudinal follow-up and to identify the biological mechanisms underlying this relationship.

Circulating plasma phospholipid fatty acid levels as a biomarker of habitual dietary fat intake: The INTERMAP/INTERLIPID Study.

BACKGROUND: Accurate assessment of fat intake is essential to examine relationships between diet and disease risk. However, estimating individual intakes of fat quantity by dietary assessment is difficult. OBJECTIVE: We assessed the association of plasma phospholipid fatty acid levels with dietary intake of fatty acids in the INTERMAP/INTERLIPID study, conducted with a standardized protocol. METHODS: The study participants were 1339 men and women ages 40-59 years from five Japanese populations one from Hawaii; four from Japan. Fatty acid intake was estimated from four standardized 24-hour dietary recalls. Plasma phospholipid fatty acid composition was analyzed by gas chromatography. We illustrated the relationship between intake and circulating fatty acid levels using Spearman's rank-correlation coefficients, mean, and median values. RESULTS: Spearman's rank-correlation coefficients between intake (g/d) and circulating fatty acid levels (µg/ml) were -0.03 to 0.21 for saturated fatty acids and monounsaturated fatty acids and -0.04 to 0.32 for trans fatty acids. The coefficients for essential n-3 and n-6 fatty acids were moderate to high, especially for eicosapentaenoic acid (EPA), 0.60; docosahexaenoic acid (DHA), 0.41; and EPA+DHA, 0.51. The circulating levels and intake of marine-derived n-3 fatty acids showed a linear association, at least for the intake of EPA+DHA up to 2.1 g/d. CONCLUSION: We observed high correlation between intake and circulating levels of marine-derived n-3 fatty acids in participants from Japanese and Japanese-American populations with high and low fish intake. Plasma phospholipid marine-derived n-3 fatty acid measurements are a simple and reliable biomarker for assessing dietary intake.

Neuropsychological Assessment of Community-Dwelling Older Adults in Almaty, Kazakhstan.

Cognitive impairment in older adults is a major public concern for Kazakhstan's aging population. We aimed to (1) administer a neuropsychological test battery (NTB) in domains relevant to aging-associated cognitive impairment in a sample of adults aged 60+ without dementia in Almaty, Kazakhstan; (2) investigate the associations between demographic factors and test performance; and (3) provide information on the distribution of NTB scores as preliminary local normative data relevant for this population. A cross-sectional evaluation of 276 participants aged 60+ in Almaty, Kazakhstan, was conducted using cognitive instruments including tests of memory, attention, language, executive functions, visuospatial abilities, and processing speed. Multiple linear regression analyses were used to examine the association of demographic factors with neuropsychological test performance. The results from the regression analysis showed that those who are younger, have more years of education, are women, and are of Russian ethnicity had significantly better performance. The current study illustrated (1) the feasibility of administering the NTB to older adults in the general population in Kazakhstan; (2) the preliminary local normative neuropsychological measures; and (3) their independent associations with age, education, gender, and ethnicity. The findings are a platform for future research on dementia and cognitive impairment in older adults in Kazakhstan.

Cross-sectional association of equol producing status with aortic calcification in Japanese men aged 40-79 years.

Equol is an isoflavone (ISF)-derived metabolite by the gut microbiome in certain individuals termed equol-producers (EP). Equol might be the critical anti-atherogenic component of ISFs. In a population-based study of 979 Japanese men aged 40-79 without cardiovascular (CVD) or chronic kidney disease, we measured the urinary levels of equol and ISFs. Aortic calcification (AC) in the entire aorta was assessed by electron-beam or multi-detector-row computed tomography. Subjects with log10 (urinary equol to daidzein concentration) > - 1.5 were classified as EP. EP was further classified as person with low- and high-equol. We analyzed the association between equol-producing status and AC presence, defined as AC score > 0, by the logistic regressions. We found that EP (50% of the sample) had significantly lower odds of AC presence (odds ratio (OR): 0.62, 95% confidence interval (CI): 0.39, 0.98) compared to non-EP. This association was independent of CVD risk factors. For the dose-response association, compared to non-EP, subjects with low and high levels of equol had ORs of 0.51 (95% CI 0.30, 0.84) and 0.67 (95% CI 0.39, 1.14) after adjusting for major CVD risk factors (p for trend = 0.06). ISFs concentrations were not significantly associated with AC presence (OR: 1.18, 95% CI: 0.82, 1.69). In conclusion, EP had a significantly lower burden of AC than non-EP, while ISFs were not associated with AC presence in Japanese men aged 40-79 years.

Potential Protective Mechanisms of S-equol, a Metabolite of Soy Isoflavone by the Gut Microbiome, on Cognitive Decline and Dementia.

S-equol, a metabolite of soy isoflavone daidzein transformed by the gut microbiome, is the most biologically potent among all soy isoflavones and their metabolites. Soy isoflavones are phytoestrogens and exert their actions through estrogen receptor-ß. Epidemiological studies in East Asia, where soy isoflavones are regularly consumed, show that dietary isoflavone intake is inversely associated with cognitive decline and dementia; however, randomized controlled trials of soy isoflavones in Western countries did not generally show their cognitive benefit. The discrepant results may be attributed to S-equol production capability; after consuming soy isoflavones, 40-70% of East Asians produce S-equol, whereas 20-30% of Westerners do. Recent observational and clinical studies in Japan show that S-equol but not soy isoflavones is inversely associated with multiple vascular pathologies, contributing to cognitive impairment and dementia, including arterial stiffness and white matter lesion volume. S-equol has better permeability to the blood-brain barrier than soy isoflavones, although their affinity to estrogen receptor-ß is similar. S-equol is also the most potent antioxidant among all known soy isoflavones. Although S-equol is available as a dietary supplement, no long-term trials in humans have examined the effect of S-equol supplementation on arterial stiffness, cerebrovascular disease, cognitive decline, or dementia.

Racial and Ethnic Differences in Cardiac Rehabilitation Participation: Effect Modification by Household Income.

Background Cardiac rehabilitation (CR) is associated with improved cardiovascular outcomes. Racial and ethnic differences in CR have been identified, but whether income may attenuate these disparities remains unknown. We evaluated (1) racial/ethnic differences in CR participation in a contemporary sample of insured US adults, and (2) assessed how household income modifies associations between race or ethnicity and CR participation. Methods and Results We identified 107 199 individuals with a CR-qualifying diagnosis between January 1, 2016 and December 31, 2018 in Optum's de-identified Clinformatics database. We evaluated associations between race or ethnicity and participation in CR, and assessed interaction between race or ethnicity and annual household income. The mean±SD age of all participants was 70.4±11.6 years; 37.4% were female and 76.0% were White race. Overall, 28 443 (26.5%) attended ≥1 CR sessions. After adjustment, compared with White individuals, the probability of attending CR was 31% lower for Asian individuals (95% CI, 27%-36%), 19% lower for Black individuals (95% CI, 16%-22%), and 43% lower for Hispanic individuals (95% CI, 40%-45%), all P<0.0001. The time to CR attendance was also significantly longer for Asian, Black, and Hispanic individuals. Associations between race or ethnicity and attendance at CR differed significantly across household income categories (P interaction=0.0005); however, Asian, Black, and Hispanic individuals were less likely to attend CR at all incomes. Conclusions In a geographically and racially diverse cohort, participation in CR was low overall, and was lowest among Asian, Black, and Hispanic candidates. Household income may impact the link between race or ethnicity and attendance at CR, but substantial racial and ethnic disparities exist across incomes.

Red blood cell fatty acid patterns from 7 countries: Focus on the Omega-3 index.

Red blood cell (RBC) fatty acid (FA) patterns are becoming recognized as long-term biomarkers of tissue FA composition, but different analytical methods have complicated inter-study and international comparisons. Here we report RBC FA data, with a focus on the Omega-3 Index (EPA + DHA in% of total FAs in RBC), from samples of seven countries (USA, Canada, Italy, Spain, Germany, South Korea, and Japan) including 167,347 individuals (93% of all samples were from the US). FA data were generated by a uniform methodology from a variety of interventional and observational studies and from clinical laboratories. The cohorts differed in size, demographics, health status, and year of collection. Only the Canadian cohort was a formal, representative population-based survey. The mean Omega-3 Index of each country was categorized as desirable (>8%), moderate (>6% to 8%), low (>4% to 6%), or very low (≤4%). Only cohorts from Alaska (treated separately from the US), South Korea and Japan showed a desirable Omega-3 Index. The Spanish cohort had a moderate Omega-3 Index, while cohorts from the US, Canada, Italy, and Germany were all classified as low. This study is limited by the use of cohorts of convenience and small sample sizes in some countries. Countries undertaking national health status studies should utilize a uniform method to measure Omega-3 FA levels.

Differential Association of Serum n-3 Polyunsaturated Fatty Acids with Various Cerebrovascular Lesions in Japanese Men.

BACKGROUND: An association between a high intake of marine-derived n-3 polyunsaturated fatty acids (n-3 PUFAs) with a lower risk of coronary heart disease was previously reported. However, the association between n-3 PUFAs and cerebrovascular lesions remains unclear. We evaluated this association in a general-population-based sample of Japanese men. METHODS: Participants were community-dwelling men (40-79 years old) living in Kusatsu City, Shiga, Japan. Serum concentrations of n-3 PUFAs, defined as the sum of eicosapentaenoic and docosahexaenoic acids, were measured via gas-liquid chromatography between 2006 and 2008. Magnetic resonance imaging was used to assess cerebrovascular lesions (including intracerebral large-artery stenosis, lacunar infarction, and microbleeds) and white matter lesions between 2012 and 2015. Logistic regression adjusting for conventional cardiovascular risk factors was used to estimate the odds ratio of prevalent cerebrovascular lesions per 1 standard deviation higher serum concentration of n-3 PUFAs. RESULTS: Of a total of 739 men, the numbers (crude prevalence in %) of prevalent cerebral large-artery stenoses, lacunar infarctions, microbleeds, and white matter lesions were 222 (30.0), 162 (21.9), 103 (13.9), and 164 (22.2), respectively. A 1 standard deviation higher concentration of n-3 PUFAs (30.5 µmol/L) was independently associated with lower odds of cerebral large-artery stenosis (multivariable-adjusted odds ratio, 0.80; 95% confidential interval, 0.67-0.97). There were no significant associations of n-3 PUFAs with the other types of lesions. CONCLUSIONS: n-3 PUFAs may have protective effects against large-artery stenosis, but not small vessel lesions, in the brain.

Association of equol producing status with aortic calcification in middle-aged Japanese men: The ERA JUMP study.

BACKGROUND: Equol, an isoflavone (ISF)-derived metabolite by the gut microbiome in certain individuals termed as equol-producers, might be the key anti-atherogenic component of ISFs. Our objective was to determine the association between equol-producing status and aortic atherosclerosis assessed as aortic calcification (AC). METHODS: This population-based study of 302 Japanese men aged 40-49, free of cardiovascular disease, examined serum levels of equol and ISFs, AC in the entire aorta by electron-beam computed tomography with Agatston method, and cardiovascular risk factors. We defined equol-producers as individuals with serum levels of equol ≥20 nM and prevalent AC as an AC score ≥ 10. We analyzed the association between equol-producing status and AC using Tobit and logistic regressions. We performed age-stratified analyses since age was a significant effect-modifier. RESULTS: The 70th to 90th percentile AC scores were 4 to 243 in equol-producers and 15 to 444 in non-producers, respectively. Overall, equol-producers (41% of the sample) had lower AC scores (-209, [95% confidence interval (CI): -455, 36]) and odds of AC (odds ratio (OR): 0.7 [95% CI: 0.4, 1.3]), although not statistically significant, compared to non-producers after controlling for cardiovascular risk factors. Among men aged 46-49, equol-producers had significantly lower AC scores (-428 [95% CI: -827, -29]). Furthermore, there were null associations between serum levels of ISFs and both AC score and the odds of AC. CONCLUSION: In middle-aged Japanese men, equol-producers had a non-significantly lower burden of aortic atherosclerosis than non-producers whereas ISFs had a null association. Studies with larger sample sizes in both sexes are warranted.

Using lipid profiling to better characterize metabolic differences in apolipoprotein E (APOE) genotype among community-dwelling older Black men.

Apolipoprotein E (APOE) allelic variation is associated with differences in overall circulating lipids and risks of major health outcomes. Lipid profiling provides the opportunity for a more detailed description of lipids that differ by APOE, to potentially inform therapeutic targets for mitigating higher morbidity and mortality associated with certain APOE genotypes. Here, we sought to identify lipids, lipid-like molecules, and important mediators of fatty acid metabolism that differ by APOE among 278 Black men ages 70-81. Using liquid chromatography-mass spectrometry methods, 222 plasma metabolites classified as lipids, lipid-like molecules, or essential in fatty acid metabolism were detected. We applied principal factor analyses to calculate a factor score for each main lipid category. APOE was categorized as ε4 carriers (n = 83; ε3ε4 or ε4ε4), ε2 carriers (n = 58; ε2ε3 or ε2ε2), or ε3 homozygotes (n = 137; ε3ε3). Using analysis of variance, the monoacylglycerol factor, cholesterol ester factor, the factor for triacylglycerols that consist mostly of polyunsaturated fatty acids, sphingosine, and free carnitine significantly differed by APOE (p < 0.05, false discovery rate < 0.30). The monoacylglycerol factor, cholesterol ester factor, and sphingosine were lower, whereas the factor for triacylglycerols that consisted mostly of polyunsaturated fatty acids was higher among ε2 carriers than remaining participants. Free carnitine was lower among ε4 carriers than ε3 homozygotes. Lower monoacylglycerols and cholesteryl esters and higher triacylglycerols that consist mostly of polyunsaturated fatty acids may be protective metabolic characteristics of APOE ε2 carriers, whereas lower carnitine may reflect altered mitochondrial functioning among ε4 carriers in this cohort of older Black men.

A Comparison of Segment-Specific and Composite Measures of Carotid Intima-Media Thickness and their Relationships with Coronary Calcium.

AIMS: The utility of carotid intima-media thickness (cIMT) as a marker for coronary heart disease is under heavy debate. This is predominantly due to the lack of a standard definition of cIMT, leading to inconsistent results. We investigated and compared the relationships of five different measures of cIMT with coronary calcium. METHODS: Japanese men aged 40-79y ( n=869) from Shiga Epidemiological Study of Subclinical Atherosclerosis were examined. Mean cIMT was measured in three segments of the carotid arteries: common carotid artery (CCAmean), internal carotid artery (ICAmean) and bifurcation (Bifmean). Mean cIMT of average values (Mean cIMT) and mean cIMT of maximum values (Mean-Max cIMT) of all segments combined were assessed. Coronary calcium was assessed as coronary artery calcification (CAC). Ordinal logistic regression was used to determine the odds ratio (OR) of higher CAC per 1 standard deviation higher cIMT measure. Analyses were adjusted for cardiovascular covariates and stratified by age quartiles. RESULTS: All cIMT measures had positive associations with CAC (p＜0.001): [OR, 95% Confidence Interval]: ICAmean [1.23, 1.07-1.42], CCAmean [1.27, 1.08-1.49], Bifmean [1.33, 1.15-1.53], Mean cIMT [1.42, 1.22-1.66], and Mean-Max [1.50, 1.28-1.75]. In age-stratified analyses, only Mean-Max cIMT maintained a significant relationship with CAC in every age quartile (p＜0.05), while CCAmean had some of the weakest associations among age quartiles. CONCLUSIONS: Mean-Max cIMT had consistently stronger associations with coronary calcium, independent of important confounders, such as age. The most oft-used measure, CCAmean, was no longer associated with coronary calcium after age-adjustment and stratification.

Potential Protective Effects of Equol (Soy Isoflavone Metabolite) on Coronary Heart Diseases-From Molecular Mechanisms to Studies in Humans.

Equol, a soy isoflavone-derived metabolite of the gut microbiome, may be the key cardioprotective component of soy isoflavones. Systematic reviews have reported that soy isoflavones have no to very small effects on traditional cardiovascular disease risk factors. However, the potential mechanistic mode of action of equol on non-traditional cardiovascular risk factors has not been systematically reviewed. We searched the PubMed through to July 2021 by using terms for equol and each of the following markers: inflammation, oxidation, endothelial function, vasodilation, atherosclerosis, arterial stiffness, and coronary heart disease. Of the 231 records identified, 69 articles met the inclusion criteria and were summarized. Our review suggests that equol is more lipophilic, bioavailable, and generally more potent compared to soy isoflavones. Cell culture, animal, and human studies show that equol possesses antioxidative, anti-inflammatory, and vasodilatory properties and improves arterial stiffness and atherosclerosis. Many of these actions are mediated through the estrogen receptor ß. Overall, equol may have a greater cardioprotective benefit than soy isoflavones. Clinical studies of equol are warranted because equol is available as a dietary supplement.

Comparing Pathological Risk Factors for Dementia between Cognitively Normal Japanese and Americans.

The Alzheimer's Disease Neuroimaging Initiative showed that Japanese had significantly lower brain Aß burden than Americans among a cognitively normal population. This cross-sectional study aimed to compare vascular disease burden, Aß burden, and neurodegeneration between cognitively normal elderly Japanese and Americans. Japanese and American participants were matched for age (±4-year-old), sex, and Apolipoprotein E (APOE) genotype. Brain vascular disease burden and brain Aß burden were measured using white matter lesions (WMLs) and 11C-labeled Pittsburgh Compound B (PiB) retention, respectively. Neurodegeneration was measured using hippocampal volumes and cortical thickness. A total of 95 Japanese and 95 Americans were recruited (50.5% men, mean age = 82). Compared to Americans, Japanese participants had larger WMLs, and a similar global Aß standardized uptake value ratio (SUVR), cortical thickness and hippocampal volumes. Japanese had significantly lower regional Aß SUVR in the anterior ventral striatum, posterior cingulate cortex, and precuneus. Cognitively normal elderly Japanese and Americans had different profiles regarding vascular disease and Aß burden. This suggests that multiple risk factors are likely to be involved in the development of dementia. Additionally, Japanese might have a lower risk of dementia due to lower Aß burden than Americans. Longitudinal follow-up of these cohorts is warranted to ascertain the predictive accuracy of these findings.

Ambient fine particulate matter exposure and incident mild cognitive impairment and dementia.

BACKGROUND/OBJECTIVE: Poor air quality is implicated as a risk factor for cognitive impairment and dementia. Few studies have examined these associations longitudinally in well-characterized population-based cohorts with standardized annual assessment of both mild cognitive impairment (MCI) and dementia. We investigated the association between estimated ambient fine particulate matter (PM2.5 ) and risk of incident MCI and dementia in a post-industrial region known for historically poor air quality. SETTING/PARTICIPANTS: Adults aged 65+ years in a population-based cohort (n = 1572). MEASUREMENTS: Census tract level PM2.5 from Environmental Protection Agency (EPA) air quality monitors; Clinical Dementia Rating (CDR)®. DESIGN: We estimated ambient PM2.5 exposure (µg/m3 , single-year and 5-year averages) by geocoding participants' residential addresses to census tracts with daily EPA PM2.5 measurements from 2002 to 2014. Using Bayesian spatial regression modeling adjusted for age, sex, education, smoking history, and household income, we examined the association between estimated PM2.5 exposure and risk of incident MCI (CDR = 0.5) and incident dementia (CDR ≥ 1.0). RESULTS: Modeling estimated single-year exposure, each 1 µg/m3 higher ambient PM2.5 was associated with 67% higher adjusted risk of incident dementia (hazard ratio [HR] = 1.669, 95% credible interval [CI]: 1.298, 2.136) and 75% higher adjusted risk of incident MCI (HR = 1.746, 95% CI: 1.518, 2.032). Estimates were higher when modeling 5-year ambient PM2.5 exposure for incident dementia (HR = 2.082, 95% CI: 1.528, 3.015) and incident MCI (HR = 3.419, 95% CI: 2.806, 4.164). CONCLUSIONS: Higher estimated ambient PM2.5 was associated with higher risk of incident MCI and dementia, particularly when considering longer-term exposure, and independent of demographic characteristics and smoking history. Targeting poor air quality may be a reasonable population-wide intervention to reduce the risk of cognitive impairment in older adults, particularly in regions exceeding current recommendations for safe exposure to PM2.5 .

The effect of soy isoflavones on arterial stiffness: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Some but not all randomized controlled trials (RCTs) of soy isoflavones showed their beneficial effect on arterial stiffness, a predictor of cardiovascular events, dementia, and all-cause mortality, independent of traditional risk factors. To test the hypothesis that supplementation of soy isoflavones reduces arterial stiffness, we performed a systematic review and meta-analysis of RCTs of soy isoflavones on arterial stiffness. METHODS: The protocol of this systematic review was registered with PROSPERO (CRD42019126128) and written in accordance with PRISMA. The PubMed, Embase, and clinicaltrials.gov databases were searched using the following criteria: human subjects, soy isoflavones as intervention, and arterial stiffness as primary outcome. A random-effects meta-analysis was used to pool estimates across studies. Standardized mean difference (SMD) was used to synthesize quantitative results. RESULTS: Among 998 articles retrieved, 8 articles met our criteria. Duration of intervention was relatively short (maximum of 12 weeks). Outcome measurements extracted were pulse wave velocity (PWV), systemic arterial compliance (SAC), augmentation index (AI), and cardio-ankle vascular index (CAVI). Soy isoflavones reduced arterial stiffness compared to placebo (standardized mean difference - 0.33, 95% confidence interval - 0.47, - 0.19). Subgroup analyses showed no difference between treatment effects for intervention duration (< 6 weeks vs. ≥ 6 weeks) or gender (women only vs. men only vs. combined). Sensitivity analysis showed no difference in the effect of soy isoflavones between PWV, CAVI, SAC, and AI. CONCLUSION: Supplementation of soy isoflavones reduced arterial stiffness. Longer duration trials with larger number of participants are warranted.

Associations of equol-producing status with white matter lesion and amyloid-ß deposition in cognitively normal elderly Japanese.

INTRODUCTION: Equol, a metabolite of a soy isoflavone transformed by the gut microbiome, is anti-oxidant and anti-amyloidogenic. We assessed the associations of equol with white matter lesion normalized to total brain volume (WML%) and amyloid beta (Aß) deposition. METHODS: From 2016 to 2018, 91 cognitively normal elderly Japanese aged 75 to 89 underwent brain magnetic resonance imaging and positron emission tomography using 11C-Pittsburgh compound-B. Serum equol was measured using stored samples from 2008 to 2012. Equol producers were defined as individuals with serum levels >0. Producers were further divided into high (> the median) and low (≤ the median) producers. RESULTS: The median (interquartile range) WML% was 1.10 (0.59 to 1.61); 24.2% were Aß positive, and 51% were equol producers. Equol-producing status (non-producers, low and high) was significantly inversely associated with WML%: 1.19, 0.89, and 0.58, respectively (trend P < .01). Equol-producing status was not associated with Aß status. DISCUSSION: A randomized-controlled trial of equol targeting WML volume is warranted.

Cross-sectional association of bone mineral density with coronary artery calcification in an international multi-ethnic population-based cohort of men aged 40-49: ERA JUMP study.

INTRODUCTION: Inverse associations of cardiovascular disease (CVD) and atherosclerosis with osteoporosis and bone mineral density (BMD) have been reported in post-menopausal women and elderly men. We aimed to investigate an association between vetebral bone density (VBD) and coronary artery cacification (CAC) in an international multi-ethnic cohort of middle-aged men in the EBCT and Risk Factor Assessment among Japanese and US Men in the Post-World-War-II birth cohort (ERA JUMP). METHODS: ERA JUMP examined 1134 men aged 40-49 (267 white, 84 black, and 242 Japanese Americans, 308 Japanese in Japan, and 233 Koreans in South Korea) free from CVD for CAC, and VBD, biomarkers of coronary atherosclerosis and BMD, respectively, with electron-beam computed tomography, and other risk factors. CAC was quantified with the Agatston method and VBD by computing the mean Hounsfield Unit (HU) value of the T12 to L3 vertebrae. To examine multivariable-adjusted associations of CAC with VBD, we used robust linear and logistic regressions. RESULTS: The mean VBD and median CAC were 175.4 HU (standard deviation: 36.3) and 0 (interquartile range: (0, 4.5)), respectively. The frequency of CAC was 19.0%. There was no significant interaction by race. VBD had a significant inverse association with CAC score (ß = -0.207, p-value = 0.005), while a 10-unit increase in VBD was significantly associated with the frequency of CAC (odds ratio (95% confidence interval) = 0.929 (0.890-0.969)). Both associations remained significant after adjusting for covariates. CONCLUSIONS: VBD had a significant inverse association with CAC in this international multi-ethnic cohort of men aged 40-49.

Associations of body composition with incident dementia in older adults: Cardiovascular Health Study-Cognition Study.

INTRODUCTION: A body of literature reported associations between late-life general adiposity measures (eg, body mass index) and dementia. Little is known about the association of late-life body composition with dementia risk. METHODS: We determined this association among cognitively normal participants from the Cardiovascular Health Study- Cognition Study. Body composition was assessed by dual-energy x-ray absorptiometry in 1994-1995. Dementia was ascertained at annual follow-up from 1998-1999 to 2013. Associations of body composition with incident dementia were assessed by the Fine-Gray model. RESULT: Among 344 participants (mean age 78, 62.2% women), body composition was significantly different between men and women, despite similar body mass indexes (BMIs). Increased dementia risk was significantly associated with lower lean mass in men and marginally with low appendicular lean mass in women. DISCUSSION: Decreased lean mass was an indicator of increased dementia risk in older adults. Studies should test whether preventing lean mass loss in older adults reduces dementia risk.

Physical activity levels in American and Japanese men from the ERA-JUMP Study and associations with metabolic syndrome.

Background: Metabolic syndrome (MetS) is a global health problem. Physical activity (PA) is a known modifiable risk factor for MetS and individual MetS components. However, the role of PA could differ between sub-populations due to differences in the variability of PA and other MetS risk factors. To examine these differences, multi-country studies with standardized outcome measurement methods across cohorts are needed. Methods: Cross-sectional PA levels (total and domain specific) in healthy middle-aged (44-56 years) men in the Risk Factor Assessment among Japanese and U.S. Men in the Post-World War II Birth Cohort (ERA-JUMP) Study (n = 730; American: n = 417; Japanese: n = 313; from population-representative samples in Pittsburgh, Pennsylvania, USA, and Kusatsu, Shiga, Japan) were compared. The relationships between PA levels and MetS (overall and specific components) in/across the American and Japanese sub-cohorts (adjusting for age, smoking, and alcohol consumption) were also assessed using the same instruments (pedometer and validated questionnaire) to measure PA in both cohorts. Results: A total of 510 individuals provided complete data on PA (American: n = 265; Japanese: n = 245). The American cohort had significantly lower mean ± SD steps/day (7878 ± 3399 steps/day) vs. the Japanese cohort (9055 ± 3797 steps/day) (p < 0.001) but had significantly higher self-reported moderate-vigorous leisure PA (American: 15.9 (7.4-30.3) metabolic task equivalent hours per week (MET-h/week) vs. Japanese: 4.0 (0-11.3) MET-h/week, p < 0.0001). In both sub-cohorts, each 1000 steps/day increase was associated with lower odds of having MetS (American: OR = 0.90, 95%CI: 0.83-0.98; Japanese: OR = 0.87, 95%CI: 0.79-0.95) and the individual MetS component of high waist circumference (American: OR = 0.86, 95%CI: 0.79-0.94; Japanese: OR = 0.87, 95%CI: 0.80-0.95). In the American cohort only, higher self-reported leisure PA (Met-h/week) was associated with lower odds of MetS and high waist circumference (OR = 0.98, 95%CI: 0.97-0.99 for MetS and waist circumference, respectively). Conclusion: Higher total step counts/day had an important protective effect on MetS prevalence in both the Japanese and American cohorts, despite differences in PA levels and other MetS risk factors. The effect of steps/day (across all intensity levels) was much greater than domain-specific moderate-vigorous PA captured by questionnaire, suggesting the need for measurement tools that can best capture total movement when examining the effects of PA on MetS development.