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BACKGROUND: Despite the emergence of SARS-CoV-2 variants and waning immunity after initial vaccination, data on antibody kinetics following booster doses, particularly those adapted to Omicron subvariants like XBB.1.5, remain limited. This study assesses the kinetics of anti-spike protein receptor-binding domain (S-RBD) IgG antibody titers post-booster vaccination in a Japanese population during the Omicron variant epidemic. METHODS: A prospective cohort study was conducted in Bizen City, Japan, from November 2023 to January 2024. Participants included residents and workers aged ≥18 years, with at least three COVID-19 vaccinations. Antibody levels were measured from venous blood samples. The study analyzed 424 participants and 821 antibody measurements, adjusting for variables such as age, sex, underlying conditions, and prior infection status. Mixed-effects models were employed to describe the kinetics of log-transformed S-RBD antibody titers. RESULTS: The study found that S-RBD antibody titers declined over time but increased with the number of booster vaccinations, particularly those adapted to Omicron and its subvariant XBB.1.5 (Pfizer-BioNTech Omicron-compatible: 0.156, 95%CI -0.032 to 0.344; Pfizer-BioNTech XBB-compatible: 0.226; 95%CI -0.051 to 0.504; Moderna Omicron-compatible: 0.279, 95%CI 0.012 to 0.546; and Moderna XBB-compatible: 0.338, 95%CI -0.052 to 0.728). Previously infected individuals maintained higher antibody titers, which declined more gradually compared to uninfected individuals (coefficient for interaction with time 0.006; 95%CI 0.001 to 0.011). Sensitivity analyses using Generalized Estimating Equations and interval-censored random intercept model confirmed the robustness of these findings. CONCLUSIONS: The study provides specific data on antibody kinetics post-booster vaccination, including the XBB.1.5-adapted vaccine, in a highly vaccinated Japanese population. The results highlight the importance of considering individual demographics and prior infection history in optimizing vaccination strategies.
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BACKGROUND: Understanding the association between the immune response and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has implications for forthcoming prevention strategies. We evaluated the association between antibody titers and the risk of infection for the general population during the Omicron-dominant phase. METHODS: This was a prospective cohort study of residents or people affiliated with institutions in Bizen City, which included 1,899 participants. We measured the titers of antibodies against SARS-CoV-2 repeatedly every 2 months from June 2022 to March 2023. Infection status was obtained from self-reported questionnaires and the official registry. We estimated risk ratios (RRs) for infection within 2 months of the date of each antibody measurement with 95% confidence intervals (CIs) based on antibody titer categories and spline functions. RESULTS: Compared with the <2,500 arbitrary unit (AU)/mL category, the 2,500-5,000, 5,000-10,000, and ≥10,000â AU/mL categories had adjusted RRs (95% CI) of 0.81 (0.61-1.08), 0.51 (0.36-0.72), and 0.41 (0.31-0.54), respectively. The spline function showed a non-linear relationship between antibody titer and risk. CONCLUSIONS: Higher antibody titers were associated with a lower risk. We demonstrate the usefulness of measuring an antibody titers to determine the appropriate timing for future vaccination.
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Global concern over COVID-19 vaccine distribution disparities highlights the need for strategic booster shots. We explored longitudinal antibody responses post-booster during the Omicron wave in a Japanese cohort, emphasizing prior infection and booster doses. This prospective cohort study included 1763 participants aged 18 years and older with at least three vaccine doses (7376 datapoints). Antibody levels were measured every 2 months. We modeled temporal declines in antibody levels after COVID-19 vaccine boosters according to prior infection status and booster doses using a Bayesian linear mixed-effects interval-censored model, considering age, sex, underlying conditions, and lifestyle. Prior infection enhanced post-booster immunity (posterior median 0.346, 95% credible interval [CrI] 0.335-0.355), maintaining antibody levels (posterior median 0.021; 95% CrI 0.019-0.023) over 1 year, in contrast to uninfected individuals whose levels had waned by 8 months post-vaccination. Each additional booster was correlated with higher baseline antibody levels and slower declines, comparing after the third dose. Female sex, older age, immunosuppressive status, and smoking history were associated with lower baseline post-vaccination antibodies, but not associated with decline rates except for older age in the main model. Prior infection status and tailored, efficient, personalized booster strategies are crucial, considering sex, age, health conditions, and lifestyle.
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Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , Feminino , Humanos , Teorema de Bayes , Estudos Prospectivos , COVID-19/prevenção & controle , Anticorpos , Anticorpos AntiviraisRESUMO
BACKGROUND: Many outbreaks of coronavirus disease 2019 have occurred in Japanese nursing homes in which residents and staff are in close daily contact. This study evaluated longitudinal changes in antibody titers in nursing homes in which clusters occurred and examined the association between antibody titer and the severe acute respiratory syndrome coronavirus 2 infection or severity. METHODS: This cohort study included 171 participants who had provided at least one antibody titer test between June 2022 and March 2023. A descriptive analysis estimated the association between the risk of infection and antibody titer level. RESULTS: The facility experienced 2 clusters during the study period that involved facility staff as the initial source of infection. Noninfected participants had less variation in antibody titer levels and a higher level of preinfection antibodies than infected participants. The risk of infection and severity was lower in participants with higher antibody titers than in those with lower titers. CONCLUSIONS: We showed the changes in antibody titers over time and the association between antibody titer and severe acute respiratory syndrome coronavirus 2 infection or severity. Vaccination schedules may need to be tailored to the dynamics of decreasing antibody titers over time and the occurrence of infectious diseases in facilities.
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Anticorpos Antivirais , COVID-19 , Casas de Saúde , SARS-CoV-2 , Humanos , Casas de Saúde/estatística & dados numéricos , COVID-19/epidemiologia , COVID-19/imunologia , Anticorpos Antivirais/sangue , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , SARS-CoV-2/imunologia , Estudos Longitudinais , Japão/epidemiologia , Estudos de Coortes , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Obesity (i.e., body mass index [BMI] of 30 kg/m2 or more) is one of the risk factors for severe COVID-19, but the findings may not be directly applicable to Asians, who have a different cutoff point for defining obesity. We thus examined the association between obesity/overweight (BMI of 25 kg/m2 or more and less than 30 kg/m2) and the risk of COVID-19 severity. METHODS: The study population included COVID-19 patients who had been enrolled in the registry of the Okayama City Public Health Center in Okayama, Japan, between March 2020 and June 2022. We included 27 820 patients who had information on BMI and prognosis, and we conducted Poisson regression analysis with robust error variance to estimate risk ratios (RRs) with 95% confidence intervals (CIs) for severe outcomes. RESULTS: Obesity and overweight were associated with the increased risk of severe COVID-19 in all age categories. The RRs (95% CI) for COVID-19 induced respiratory failure compared to the normal weight category were 1.57 (1.31-1.88) for overweight and 2.45 (1.90-3.15) for obesity. CONCLUSIONS: Both obesity and overweight were associated with increased risk of severe COVID-19. This study suggests the importance of the overweight category to predict the risk of severe COVID-19 in Asians.
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COVID-19 , Sobrepeso , Humanos , Sobrepeso/complicações , Sobrepeso/epidemiologia , COVID-19/epidemiologia , COVID-19/complicações , Japão/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Fatores de Risco , Índice de Massa Corporal , PrognósticoRESUMO
Both peripartum cardiomyopathy (PPCM) and takotsubo syndrome (TTS) are diagnoses of exclusion and are thus considered a heterogeneous disease group. TTS is generally triggered by psychogenic or physical stress. Recently, the anti-angiogenic factor cleaved prolactin has been noted as a cause of PPCM, but the precise mechanisms of these diseases remain unexplained. An 87-year-old female with a past surgical history, including transsphenoidal endoscopic surgery to remove a pituitary prolactinoma, recently underwent surgery to repair a left-sided femoral neck fracture and developed dyspnea followed by back pain; shortly after, she became embarrassed by fecal incontinence. Her initial electrocardiogram showed T wave inversions with QT prolongation leading to sustained ventricular tachycardia. No obstructive coronary artery disease was found on emergent coronary angiography, and the left ventriculography findings were consistent with TTS. After acute-phase treatment, she was diagnosed with recurrent prolactinoma based on her head magnetic resonance imaging findings. This patient's high levels of prolactin may have played a role in the pathogenesis of TTS. Learning objective: Peripartum cardiomyopathy and takotsubo syndrome (TTS) are diagnosed by exclusion, and their precise mechanisms remain unknown. We present a case of TTS associated with a prolactinoma.
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Vacinas contra COVID-19 , COVID-19 , Humanos , Japão/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2RESUMO
Abstract Spinal cord injury (SCI) is a serious neurological disorder, with the consequent disabilities conferred by this disorder typically persisting for life. Multilineage-differentiating stress-enduring (Muse) cells are endogenous stem cells that can be collected from various tissues as well as from mesenchymal stem cells (MSCs); additionally, these Muse cells are currently being used in clinical trials. The anti-inflammatory effect of stem cell transplantation prevents secondary injuries of SCI; however, its effect on Muse cells remains unclear. In this study, we aimed to compare the anti-inflammatory effects of adipose (AD)- and bone marrow (BM)-Muse cells that were isolated from mice (6-week-old C57BL/6J) following intralesional administration during the acute phase of SCI. Flow cytometry was used to isolate Muse cells from AD and BM MSCs. The percentage of Muse cells was 3.9 and 2.7% for AD and BM MSCs, respectively. To examine cell viability, Muse cells were incubated under H2O2-induced oxidative stress conditions. Overall, AD-Muse cells exhibited higher viability than BM-Muse cells (p = 0.032). In enzyme-linked immunosorbent assay analysis, AD-Muse cells displayed greater secretion of brain-derived neurotrophic factor (BDNF; p = 0.008), vascular endothelial growth factor (p = 0.032), and hepatocyte growth factor (p = 0.016). DNA microarray analysis revealed higher expression of Bdnf, neurotrophin-3 (Ntf3), nerve growth factor (Ngf), pleiotrophin (Ptn), and midkine (Mdk) in AD-Muse cells than in BM-Muse cells. To assess their anti-inflammatory effects in vitro, Muse cells and macrophages were co-cultured, and the levels of cytokines (tumor necrosis factor [TNF] α and interleukin [IL] 10) were measured in the medium. Consequently, we found that TNFα levels were lower in AD-Muse cells than in BM-Muse cells (p = 0.009), and IL10 levels were higher in AD-Muse cells than in BM-Muse cells (p = 0.008). Further, we induced moderate injuries via contusion of the spinal cord at the T10 level; Muse cells were transplanted intralesionally 7 days post-SCI. The number of surviving cells, alongside the number of CD86+ (M1 inflammatory effect), and CD206+ (M2 anti-inflammatory effect) macrophages in the spinal cord were measured 7 days post-transplantation. The number of surviving AD-Muse cells was higher than the number of surviving BM-Muse cells (ratio of AD-Muse/BM-Muse = 2.5, p > 0.05). The M1/M2 ratio in the AD-Muse cell-group (0.37) was lower than that in the control (phosphate-buffered saline) group (3.60, p = 0.008). The lesion area in the AD-Muse cell group was smaller than that in the BM-non-Muse (p = 0.049) and control groups (p = 0.012). As AD-Muse cells conferred a higher cell survival and neurotrophic factor secretion ability in vitro, AD-Muse cells demonstrated reduced inflammation after SCI. Overall, intralesional AD-Muse cell therapy is a potential therapeutic candidate that is expected to exhibit anti-inflammatory effects following acute SCI.
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Transplante de Células-Tronco Mesenquimais , Traumatismos da Medula Espinal , Camundongos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Medula Óssea/metabolismo , Medula Óssea/patologia , Fator A de Crescimento do Endotélio Vascular , Alprostadil , Peróxido de Hidrogênio , Camundongos Endogâmicos C57BL , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/patologia , Medula Espinal/metabolismo , Anti-InflamatóriosRESUMO
BACKGROUND: Association between vitamin D levels and the occurrence of depression are not always consistent. The present cohort study aimed to determine this association in older adults, using a method for measuring vitamin D levels which is more accurate than those used in previous studies. METHODS: Participants were 3447 individuals aged 40-74 years without depressive symptoms at baseline who participated in the 5-year follow-up survey. The baseline investigation, including a self-administered questionnaire survey and blood collection, was conducted in 2011-2013. Plasma 25-hydroxyvitamin D (25[OH]D) levels were measured, and divided into overall quartiles summed up by sub-quartiles and stratified by age, sex, and season. The outcome was depressive symptoms determined by the CES-D (11-item, cut-off score of 6/7) 5 years later. Covariates were demographics, lifestyles, baseline CES-D score, and disease history. RESULTS: Mean plasma 25(OH)D levels were 58.0 nmol/L in men and 45.7 in women (P < 0.0001), and cumulative incidences of depressive symptoms were 249/1577 (15.8 %) in men and 313/1870 (16.7 %) in women (P = 0.4526). The lower 25(OH)D quartile group had higher adjusted ORs in men and women combined (P for trend = 0.0107) and women (P for trend = 0.0003), but not in men. Adjusted ORs of the lowest quartile group were significantly higher than the highest group in men and women combined (OR = 1.39, 95 % CI: 1.06-1.81) and women (OR = 1.89, 95 % CI: 1.31-2.72). LIMITATION: Depressive symptoms were self-reported. CONCLUSIONS: Low vitamin D levels were associated with a high risk of depressive symptoms, especially in women. Women are thus considered a major target for preventing vitamin D deficiency to address depression.
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Depressão , Deficiência de Vitamina D , Vitamina D , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Coortes , Depressão/epidemiologia , População do Leste Asiático , Vitamina D/sangue , VitaminasRESUMO
We developed a diagnostic method for repeat expansion diseases using a long-read sequencer to improve currently available, low throughput diagnostic methods. We employed the real-time target enrichment system of the nanopore GridION sequencer using the adaptive sampling option, in which software-based target assignment is available without prior sample enrichment, and built an analysis pipeline that prioritized the disease-causing loci. Twenty-two patients with various neurological and neuromuscular diseases, including 12 with genetically diagnosed repeat expansion diseases and 10 manifesting cerebellar ataxia, but without genetic diagnosis, were analyzed. We first sequenced the 12 molecularly diagnosed patients and accurately confirmed expanded repeats in all with uniform depth of coverage across the loci. Next, we applied our method and a conventional method to 10 molecularly undiagnosed patients. Our method corrected inaccurate diagnoses of two patients by the conventional method. Our method is superior to conventional diagnostic methods in terms of speed, accuracy, and comprehensiveness.
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The primary focus of this study was to explore the parenting attitudes that predict abusive parenting among incarcerated mothers in Japan. Data analyzed on 63 incarcerated mothers who had the legal custody of the youngest child revealed that belief in corporal punishment significantly predicted abusive parenting. The data further revealed that the impact of adverse childhood experiences and the parenting style of an intimate partner remained significant in predicting the risk of abusive parenting. These multiple risk factors affecting child abuse perpetration indicate the need to develop a multi-dimensional intervention in prison settings to address those multiple issues.
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BACKGROUND: Falls are important causes of injury and mortality in older people, and associated medical costs can be enormous. Physical activity (PA) is a potential preventive factor for falls. However, few studies have examined the effect of different types of PA on fall prevention. This study aimed to evaluate the association between PA levels and the incidence of recurrent falls by type of PA in middle-aged and older people. METHODS: This cohort study targeted 7,561 community-dwelling individuals aged 40-74 years who did not experience recurrent falls in the year before baseline. Information on PA levels, demographics, body size, lifestyle, and fall/disease history was obtained using a self-administered questionnaire in the baseline survey. Levels of total PA, leisure-time PA, and non-leisure-time PA (occupation, commuting, and housework) were estimated using metabolic equivalent (MET) scores (MET-h/day; hours spent on a given activity per day multiplied by its MET intensity). PA levels were categorized into four groups. Falls were recorded as none, once, or twice or more (recurrent falls). The outcome of the study was the incidence of recurrent falls in the past year before a survey conducted 5 years after the baseline survey. Logistic regression analyses were performed to calculate odds ratios for recurrent falls. RESULTS: Higher total PA and non-leisure-time PA levels were associated with a higher risk of recurrent falls (P for trend = 0.0002 and 0.0001, respectively), with the highest total PA and non-leisure-time PA groups having a significantly higher adjusted OR (1.96 [95%CI:1.33-2.88] and 2.15 [95%CI:1.48-3.14], respectively) relative to the lowest group (reference). As for leisure-time PA, the medium group had a significantly lower adjusted OR (0.70 [95%CI:0.49-0.99]) relative to the reference group. By sex, the adjusted OR in the medium leisure-time PA group was significantly lower relative to the reference group in women (0.50 [95%CI: 0.29-0.85]) but not in men. CONCLUSIONS: Medium level leisure-time PA reduces the risk of recurrent falls in middle-aged and older people, whereas higher level non-leisure-time PA is associated with a higher risk of recurrent falls.
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BACKGROUND: The Inception Cohort Registry Study of Patients with Crohn's Disease aimed to clarify clinical characteristics and disease course of newly diagnosed Crohn's disease patients in Japan throughout a 4-year period. Results from an interim analysis of the largest nation-wide registry study that covers approximately 1% of Crohn's disease patient population in Japan are reported. METHODS: This prospective, observational registry study was conducted at 19 tertiary centers in Japan. Patients newly diagnosed with Crohn's disease after June 2016 (age ≥ 16 years at informed consent) were enrolled between December 17, 2018 and June 30, 2020. Patient demographics, diagnostic procedures and categories, disease location and lesion behavior (Montreal classification) at the time of diagnosis were recorded. RESULTS: Of 673 patients enrolled, 672 (99.9%) were analyzed (458: men, 214: women), male-to-female ratio: 2.1, median age at diagnosis 25 (range 13-86) years; peak age of disease diagnosis: 20-24 years. Most common disease location was L3 (ileocolonic; 60.1%). Non-stricturing, non-penetrating (B1) disease was most common behavior (62.8%); 48.9% reported perianal lesions. Notably, age-wise analysis revealed disease phenotypes varied between patients aged < 40 and ≥ 40 years in terms of male-to-female ratio (2.5/1.3)/disease location (L3: 66.3%/37.0%)/disease behavior (B1: 66.4%/50.0%)/perianal lesion: (55.7%/20.5%) at Crohn's disease diagnosis, respectively. CONCLUSIONS: Interim analysis of this nation-wide Inception Cohort Registry Study of Patients with Crohn's Disease revealed the demographics and disease characteristics of newly diagnosed Crohn's disease patients in Japan and demonstrated that disease phenotype varied between patients aged < 40 and ≥ 40 years, serving as important information for management of individual patients.
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Doença de Crohn , Feminino , Humanos , Masculino , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Doença de Crohn/patologia , Estudos Prospectivos , Japão/epidemiologia , Sistema de Registros , Progressão da DoençaRESUMO
The obligate pollination mutualism between figs (Ficus, Moraceae) and pollinator wasps (Agaonidae, Hymenoptera) is a classic example of cospeciation. However, examples of phylogenetic incongruencies between figs and their pollinators suggest that pollinators may speciate by host shifting. To investigate the mechanism of speciation by host shifting, we examined the phylogenetic relationships and population genetic structures of six closely related fig species and their pollinators from southern China and Taiwan-Ryukyu islands using various molecular markers. The results revealed 1) an extraordinary case of pollinator sharing, in which five distinct fig species share a single pollinator species in southern China; 2) two types of copollination, namely, sympatric copollination by pollinator duplication or pollinator migration, and allopatric copollination by host migration and new pollinator acquisition; 3) fig species from southern China have colonized Taiwan repeatedly and one of these events has been followed by host shifting, reestablishment of host specificity, and pollinator speciation, in order. Based on our results, we propose a model for pollinator speciation by host shifting in which the reestablishment of host-specificity plays a central role in the speciation process. These findings provide important insights into understanding the mechanisms underlying pollinator speciation and host specificity in obligate pollination mutualism.
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Ficus , Vespas , Animais , Ficus/genética , Filogenia , Polinização , Simbiose , Vespas/genéticaRESUMO
OBJECTIVE: Although physical activity (PA) in late life is considered a preventive factor for dementia, effects of different types of PAs on the development of dementia in early old age are unclear. This study aimed to determine the effect of leisure-time and non-leisure-time PAs on dementia risk in middle-aged and older adults during an 8-year follow-up. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: Participants were 13,773 community-dwelling individuals aged 40-74 years who completed the baseline self-administered questionnaire survey of the Murakami cohort study in 2011-2013. METHODS: Main predictors were leisure-time and non-leisure-time (commute, occupational work, and housework) PAs as assessed by MET score (MET-hour/d). The outcome was newly developed dementia determined using a long-term care insurance database. Covariates included demographics, lifestyle, body size, disease history, and PA level. Hazard ratios (HRs) were calculated using Cox proportional hazards models. RESULTS: Mean age of participants was 59.0 (SD 9.3) years. Higher levels of leisure-time PA were associated with lower HRs (adjusted P for trend <.001), with all tertiles having significantly lower HRs (low: 0.71, 95% CI 0.51-0.99; medium: 0.59, 95% CI 0.43-0.81; high: 0.55, 95% CI 0.41-0.75) relative to the reference (zero). Higher quartiles of non-leisure-time PA were associated with lower adjusted HRs for dementia (adjusted P for trend < .001), with the second-fourth quartiles having significantly lower HRs (second: 0.73, 95% CI 0.54-0.98; third: 0.59, 95% CI 0.43-0.81; fourth: 0.55, 95% CI 0.41-0.75) relative to the lowest quartile. These associations were robust regardless of sex and age group. CONCLUSIONS AND IMPLICATIONS: Both leisure-time and non-leisure-time PAs are independently and robustly associated with a reduced risk of dementia.
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Demência , Vida Independente , Idoso , Estudos de Coortes , Demência/epidemiologia , Demência/prevenção & controle , Exercício Físico , Humanos , Atividades de Lazer , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Income inequality has dramatically increased worldwide, and there is a need to re-evaluate the association between socio-economic status (SES) and depression. Relative contributions of household income and education to depression, as well as their interactions, have not been fully evaluated. This study aimed to examine the association between SES and depressive symptoms in Japanese adults, focusing on interactions between education and household income levels. METHODS: This cross-sectional study used data from baseline surveys of two cohort studies. Participants were 38,499 community-dwelling people aged 40-74 years who participated in baseline surveys of the Murakami cohort study (2011-2012) and Uonuma cohort study (2012-2015) conducted in Niigata Prefecture, Japan. Information regarding marital status, education level, household income, occupation, activities of daily living (ADL), and history of cancer, myocardial infarction, stroke, and diabetes was obtained using a self-administered questionnaire. Depressive symptoms were examined using the Center for Epidemiologic Studies Depression Scale (CES-D). Logistic regression analysis was used to obtain odds ratios (ORs). Covariates included age, sex, marital status, education, household income, occupation, ADL, and disease history. RESULTS: Individuals with higher education levels had lower ORs (adjusted P for trend = 0.0007) for depressive symptoms, independently of household income level. The OR of the university-or-higher group was significantly lower than that of the junior high school group (adjusted OR = 0.79). Individuals with lower household income levels had higher ORs (adjusted P for trend< 0.0001) for depressive symptoms, independently of education level. The type of occupation was not associated with depressive symptoms. In subgroup analyses according to household income level, individuals with higher education levels had significantly lower ORs in the lowest- and lower-income groups (adjusted P for trend = 0.0275 and 0.0123, respectively), but not in higher- and highest-income groups (0.5214 and 0.0915, respectively). CONCLUSIONS: Both education and household income levels are independently associated with the prevalence of depressive symptoms, with household income levels showing a more robust association with depressive symptoms than education levels. This suggests that a high household income level may offset the risk of depressive symptoms from having a low education level.
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Atividades Cotidianas , Depressão , Adulto , Idoso , Estudos de Coortes , Estudos Transversais , Depressão/epidemiologia , Humanos , Renda , Japão/epidemiologia , Pessoa de Meia-Idade , PrevalênciaRESUMO
OBJECTIVES: Coffee, green tea, and caffeine are potential preventive factors for dementia, but the underlying evidence is insufficient. This study aimed to examine associations between the consumption of coffee, green tea, and caffeine and dementia risk in middle-aged and older people. METHODS: This was a cohort study with an 8.0-year follow-up. Participants were community-dwelling individuals (n = 13,757) aged 40-74 years. A self-administered questionnaire survey was conducted in 2011-2013. Predictors were the consumption of coffee/green tea, from which caffeine consumption was estimated. The outcome was incident dementia obtained from the long-term care insurance database. Covariates were demographic factors, body mass index, physical activity, energy, smoking, drinking, and disease history. Adjusted hazard ratios (HRs) were calculated using Cox proportional hazards models. HRs were also calculated using a Cox model with delayed entry. RESULTS: The number of dementia cases during the study period was 309. Participants with higher coffee consumption had lower HRs (adjusted p for trend = 0.0014), with the fifth quintile (≥326 ml/day) having a significantly lower HR (0.49, 95% confidence interval [CI]: 0.30-0.79) than the first quintile (<26 ml/day, reference). Similarly, participants with higher caffeine consumption had a significantly lower HR (adjusted p for trend = 0.0004) than the reference. The Cox model with delayed entry yielded similar results. These associations were significant in men, but not in women. Moreover, participants who consumed 2-2.9 cups/day and ≥3 cups/day of coffee had lower HRs (0.69, 95% CI: 0.48-0.98 and 0.53, 95% CI: 0.31-0.89, respectively) than those who consumed 0 cup/day. The association between green tea consumption and reduced dementia risk was significant (adjusted p for trend = 0.0146) only in the 60-69 years age subgroup. CONCLUSIONS: High levels of coffee and caffeine consumption were significantly associated with a reduced dementia risk in a dose-dependent manner, especially in men. Moreover, coffee consumption of ≥3 cups/day was associated with a 50% reduction in dementia risk.