Aya Higashiyama’s research while affiliated with Wakayama Medical University and other places

Background Alzheimer's disease (AD) is driven by amyloid-β (Aβ) plaque accumulation, but the mechanisms behind this process remain unclear. Omega-3 fatty acids, particularly docosahexaenoic acid (DHA), may offer protective effects, though their relationship with Aβ accumulation is not fully understood. Objective This study investigated whether serum DHA and eicosapentaenoic acid (EPA) levels, measured 6–9 years before imaging, were inversely associated with cerebral Aβ deposition in cognitively normal older adults in Japan, a population known for high omega-3 intake. We focused on individuals identified as Aβ-positive based on positron emission tomography (PET) scans, as they are at higher risk for AD progression, to assess DHA's potential in mitigating early amyloid pathology. Methods An analytical sample of 97 older adults (75–89 years) from the Suita Study was analyzed. Serum DHA and EPA levels were assessed between 2008 and 2012, and amyloid PET was performed between 2016 and 2019. Multiple regression analyses were conducted, adjusting for age, sex, APOE4 status, and cardiometabolic disease. Results Among 97 participants (49% males, 8.2% APOE4 carriers), 37.1% (n = 36) had cardiometabolic disease, and 29.8% (n = 29) were Aβ positive. In Aβ-positive individuals, higher serum DHA levels were significantly associated with lower Aβ deposition independent of age, sex and APOE4 status (standardized β = -0.423, p = 0.030). This became non-significant after additionally adjusting for cardiometabolic disease (β = -0.382, p = 0.059). No significant association was found between EPA and Aβ deposition. Conclusions Higher long-term DHA levels may help reduce Aβ accumulation in those at risk for AD, supporting its potential role in early prevention.

Background: Deterioration in lifestyle associated with poor mental health could be an important concern during the coronavirus disease 2019 (COVID-19) pandemic. However, few studies have investigated the association between mental health status and lifestyle changes during the pandemic in nationwide Japanese general population. Methods: This cross-sectional study was conducted using the data among 1,546 participants of the follow-up study of NIPPON DATA2010 in 2021. Recent mental status, as assessed using the Kessler 6 (K6) scale, and lifestyle changes compared to before the pandemic were determined using self-reported questionnaires. Some lifestyle changes such as decreased physical activity were defined as undesirable, whereas others such as decreased alcohol drinking were defined as desirable. The participants were divided into three groups based on the K6 scores: the K6<5, 5≤K6<9, and K6≥9 groups. The odds ratios (ORs) and 95% confidence intervals (CIs) of the K6 groups for each lifestyle change compared with that in the K6<5 group were estimated after adjusting for possible confounders. Results: The ORs of the K6≥9 group for all undesirable lifestyle changes were significantly high, especially increased alcohol drinking (OR 4.64; 95% CI, 2.71–7.93), and decreased physical activity (OR 4.63; 95% CI, 3.29–6.52). Among the desirable changes, the OR of the 5≤K6<9 group was significantly high for increased eating home cooking. Conclusions: Poor mental health showed a significant association with undesirable lifestyle changes, especially increased alcohol drinking and decreased physical activity, in a nationwide general Japanese population during the COVID-19 pandemic. Fullsize Image

We examined the effect of sex on the relationship between obesity and hypertension among Japanese people, who generally have a lower prevalence of obesity than Westerners. We analyzed the results of specific health checkups for Japanese aged 40–74 years (688,306 men and 891,191 women) obtained in 2011. The participants were divided into four age groups (40–49, 50–59, 60–69, and 70–74 years) and five body mass index (BMI) categories (≤ 24.9 [non-overweight/obesity], 25.0–26.9 and 27.0–29.9 [overweight], 30.0–34.9 and ≥ 35.0 kg/m ² [obesity]). The odds ratio for hypertension in each BMI category was calculated using normal weight as the reference. The prevalence of hypertension was 26.8%–65.5% for men and 17.6%–53.6% for women in the overweight or obesity categories in the 40–49 age group, and 72.0%–88.7% for men and 70.1%–90.6% for women in the 70–74 age group. In women aged 40–49, the prevalence of hypertension in each BMI category was approximately 10% lower than that in men, but there was almost no difference between men and women in the 70–74 age group. On the other hand, the odds ratio for hypertension was higher in women than in men across all BMI categories and age groups. A stronger relationship between obesity and hypertension was observed in women than in men in all age groups. Japanese women have not been the target of studies for obesity, but more attention should be paid to Japanese women with obesity.

Background: Dehydration, a risk factor for ischemic cerebrovascular diseases, is common in summer; however, the incidence of ischemic diseases is not necessarily higher in summer. Therefore, this study aimed to clarify the relationships between serum osmolarity, hematocrit, daily non-alcohol drink (NAD) intake and factors such as season and age as risk factors for dehydration. Method: Participants (703 women and 306 men) in the follow-up survey, in 2012 and 2013, of the Kobe Orthopedic and Biomedical Epidemiologic (KOBE) Study, consisting of healthy individuals living in Kobe, Japan, were categorized into two groups based on the examination month: the warmer and colder seasons. Multivariate analyses were conducted to examine disparities in serum osmolarity, hematocrit, and NAD intake between these two groups. Results: The colder season was found to be negatively correlated with serum osmolarity and NAD intake, but positively correlated with hematocrit, even after adjusting for relevant factors. Age was independently associated with serum osmolarity, but not with hematocrit and NAD intake. Conclusions: This study suggests that intra-vascular volume depletion is more likely in the colder season despite lower serum osmolarity compared to the warmer season. Age-related increases in serum osmolarity without a corresponding rise in water intake may contribute to this. These findings support the importance of addressing dehydration in the colder season, particularly in older adults.

Objectives Dehydration, a risk factor for ischemic cerebrovascular diseases, is common in summer; however, the incidence of ischemic diseases is not necessarily higher in summer. The phenomenon may be influenced by the differences in the susceptibility to vascular dehydration based on the season. Therefore, this study aimed to distinguish types of dehydration in colder and warmer seasons by analyzing serum osmolarity, hematocrit, and daily non-alcohol drink (NAD) intake. Methods Participants in the Kobe Orthopedic and Biomedical Epidemiologic (KOBE) Study, consisting of healthy individuals, were categorized into two groups based on the examination month: the warmer and colder seasons. Multivariate analyses were conducted to examine disparities in serum osmolarity, hematocrit, and NAD intake between these two groups. Results Participant ratios by age group and the seasons (warmer season/colder season) were as follows: Women under 50 (35/62), 50-60 (77/126), 60-70 (123/170), over 70 (58/52); Men under 50 (14/17), 50-60 (22/36), 60-70 (57/71), over 70 (55/34). The colder season was found to be negatively correlated with serum osmolarity and NAD intake, but positively correlated with hematocrit, even after adjusting for relevant factors. Age was independently associated with serum osmolarity, but not with hematocrit and NAD intake. Conclusions This study highlights that vascular dehydration is more likely in the colder season despite lower serum osmolarity than the warmer season. Age-related increases in serum osmolarity without a corresponding rise in water intake may contribute to this. These findings emphasize the importance of addressing dehydration in the colder season, particularly in older adults. Key messages • The colder season showed a negative correlation with serum osmolarity and NAD intake but a positive correlation with hematocrit. • Raising awareness about the importance of hydration during winter may be essential.

Background/Objectives: Equol has protective effects against coronary artery disease and dementia by strongly binding to estrogen receptor beta, whereas the intake of soy isoflavone alone does not always confer such protective effects. Equol production is completely dependent on the existence of equol-producing gut microbiota. The effects of equol-producing status on the cerebrovascular diseases remain unclear. The current study was aimed to investigate the association of equol-producing status with the development of stroke and its neurological prognosis. Methods: Frequencies of equol producers were compared between healthy subjects (HS) registered in the Suita Study and patients with acute stroke admitted to our stroke center from September 2019 to October 2021 in a retrospective cohort study. Results: The proportion of HSs and patients with ischemic stroke who were equol producers did not significantly differ (50/103 [48.5%] vs. 60/140 [42.9%], p = 0.38). However, cardioembolic stroke was significantly associated with low a prevalence of equol producers (adjusted odds ratio [aOR] 0.46, 95% confidence interval [CI] 0.21–0.99, p = 0.05). A higher left atrial volume index was observed in equol nonproducers (46.3 ± 23.8 vs. 36.0 ± 11.6 mL/m², p = 0.06). The equol nonproducers had a significantly higher prevalence of atrial fibrillation than the equol producers (27.5% vs. 13.3%, p = 0.04). Furthermore, the equol producers exhibited a significantly favorable functional outcome upon discharge (aOR 2.84, 95% CI 1.20–6.75, p = 0.02). Conclusions: Equol is a promising candidate for interventions aiming to reduce the risk of CES and atrial dysfunction, such as atrial fibrillation and improve neurological prognosis after ischemic stroke.

In 2022, the Japan Atherosclerosis Society (JAS) updated its prevention guidelines, the “Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2022” (JAS2022GL), expanding its scope from coronary artery disease (CAD) to atherosclerotic cardiovascular diseases (ASCVDs), including atherothrombotic stroke. The following year, the Japanese Circulation Society (JCS) updated its guidelines for primary prevention entitled “JCS 2023 Guideline on the Primary Prevention of Coronary Artery Disease” (JCS2023GL). Since those publications, scientific advancements in relevant fields have continued. This review article outlines the current recommendations provided by the guidelines, provides background information supporting these recommendations, introduces scientific findings subsequent to prior publications, and discusses future directions on select topics for the primary prevention of CVD. The topics covered in this review are traditional risk factors, including dyslipidemia and hypertension, the application of comprehensive risk stratification or risk scoring systems, patient-specific topics, salt and alcohol, and environmental factors. These topics were deliberate and selected by the authors, who were involved in the compilation of either or both JAS2022GL and JCS2023GL. This review not only emphasizes the pivotal role of continuously updated guidelines in shaping clinical practice but also stresses the urgent need for ongoing research to bridge existing knowledge and practice gaps.