Mao Shibata

Alexithymia is associated with greater risk of chronic pain and negative affect and with lower life satisfaction in a general population: the Hisayama Study.

Introduction Chronic pain is a significant health problem worldwide, with a prevalence in the general population of approximately 40%. Alexithymia — the personality trait of having difficulties with emotional awareness and self-regulation — has been reported to contribute to an increased risk of several chronic diseases and health conditions, and limited research indicates a potential role for alexithymia in the development and maintenance of chronic pain. However, no study has yet examined the associations between alexithymia and chronic pain in the general population. Methods We administered measures assessing alexithymia, pain, disability, anxiety, depression, and life satisfaction to 927 adults in Hisayama, Japan. We classified the participants into four groups (low-normal alexithymia, middle-normal alexithymia, high-normal alexithymia, and alexithymic) based on their responses to the alexithymia measure. We calculated the risk estimates for the criterion measures by a logistic regression analysis. Results Controlling for demographic variables, the odds ratio (OR) for having chronic pain was significantly higher in the high-normal (OR: 1.49, 95% CI: 1.07–2.09) and alexithymic groups (OR: 2.56, 95% CI: 1.47–4.45) compared to the low-normal group. Approximately 40% of the participants belonged to these two high-risk groups. In the subanalyses of the 439 participants with chronic pain, the levels of pain intensity, disability, depression, and anxiety were significantly increased and the degree of life satisfaction was decreased with elevating alexithymia categories. Conclusions The findings demonstrate that, in the general population, higher levels of alexithymia are associated with a higher risk of having chronic pain. The early identification and treatment of alexithymia and negative affect may be beneficial in preventing chronic pain and reducing the clinical and economic burdens of chronic pain. Further research is needed to determine if this association is due to a causal effect of alexithymia on the prevalence and severity of chronic pain.

Association Between Diabetes and Hippocampal Atrophy in Elderly Japanese: The Hisayama Study.

OBJECTIVE To investigate the association between diabetes and brain or hippocampal atrophy in an elderly population. RESEARCH DESIGN AND METHODS A total of 1,238 community-dwelling Japanese subjects aged ≥65 years underwent brain MRI scans and a comprehensive health examination in 2012. Total brain volume (TBV), intracranial volume (ICV), and hippocampal volume (HV) were measured using MRI scans for each subject. We examined the associations between diabetes-related parameters and the ratios of TBV to ICV (an indicator of global brain atrophy), HV to ICV (an indicator of hippocampal atrophy), and HV to TBV (an indicator of hippocampal atrophy beyond global brain atrophy) after adjustment for other potential confounders. RESULTS The multivariable-adjusted mean values of the TBV-to-ICV, HV-to-ICV, and HV-to-TBV ratios were significantly lower in the subjects with diabetes compared with those without diabetes (77.6% vs. 78.2% for the TBV-to-ICV ratio, 0.513% vs. 0.529% for the HV-to-ICV ratio, and 0.660% vs. 0.676% for the HV-to-TBV ratio; all P < 0.01). These three ratios decreased significantly with elevated 2-h postload glucose (PG) levels (all P for trend <0.05) but not fasting plasma glucose levels. Longer duration of diabetes was significantly associated with lower TBV-to-ICV, HV-to-ICV, and HV-to-TBV ratios. The subjects with diabetes diagnosed in midlife had significantly lower HV-to-ICV and HV-to-TBV ratios than those without and those diagnosed in late life. CONCLUSIONS Our data suggest that a longer duration of diabetes and elevated 2-h PG levels, a marker of postprandial hyperglycemia, are risk factors for brain atrophy, particularly hippocampal atrophy.

Day-to-Day Blood Pressure Variability and Risk of Dementia in a General Japanese Elderly Population: The Hisayama Study

Background: Several observational studies have reported that higher visit-to-visit blood pressure variability is a risk factor for cognitive impairment and dementia. However, no studies have investigated the association of day-to-day blood pressure variability assessed by home blood pressure measurement with the development of dementia. Methods: A total of 1674 community-dwelling Japanese elderly without dementia, ≥60 years of age, were followed up for 5 years (2007–2012). Home blood pressure was measured 3 times every morning for a median of 28 days. Day-to-day systolic (SBP) and diastolic blood pressure variabilities, calculated as coefficients of variation (CoV) of home SBP and diastolic blood pressure, were categorized into quartiles. The hazard ratios and their 95% confidence intervals of the CoV levels of home blood pressure on the development of all-cause dementia, vascular dementia (VaD), and Alzheimer disease (AD) were computed with a Cox proportional hazards model. Results: During the follow-up, 194 subjects developed all-cause dementia; of these, 47 had VaD and 134 had AD. The age- and sex-adjusted incidences of all-cause dementia, VaD, and AD increased significantly with increasing CoV levels of home SBP (all P for trend <0.05). These associations remained unchanged after adjustment for potential confounding factors, including home SBP. Compared with subjects in the first quartile of CoV levels of home SBP, the risks of the development of all-cause dementia, VaD, and AD were significantly higher in those in the fourth quartile (hazard ratio=2.27, 95% confidence interval=1.45–3.55, P<0.001 for all-cause dementia; hazard ratio=2.79, 95% confidence interval=1.04–7.51, P=0.03 for VaD; hazard ratio=2.22, 95% confidence interval=1.31–3.75, P<0.001 for AD). Similar associations were observed for CoV levels of home diastolic blood pressure. Meanwhile, home SBP levels were significantly associated with the risk of VaD but not with the risks of all-cause dementia and AD. There was no interaction between home SBP levels and CoV levels of home SBP on the risk of each subtype of dementia. Conclusions: Our findings suggest that increased day-to-day blood pressure variability is, independently of average home blood pressure, a significant risk factor for the development of all-cause dementia, VaD, and AD in the general elderly Japanese population.

Serum Angiopoietin-Like Protein 2 Is a Novel Risk Factor for Cardiovascular Disease in the Community

Objective—Angiopoietin-like protein 2 (ANGPTL2), a proinflammatory mediator, has been reported to accelerate the development of insulin resistance, endothelial dysfunction, and atherosclerosis in mice. However, no cohort studies have examined the relationship between serum ANGPTL2 levels and the development of cardiovascular disease (CVD) in a general population. Approach and Results—A total of 3005 community-dwelling Japanese aged ≥40 years without a history of CVD were divided into 4 groups according to the quartiles of serum ANGPTL2 concentrations (Q1, lowest and Q4, highest) and followed up for 10 years. The hazards ratios and their 95% confidence intervals for the development of CVD (coronary heart disease or stroke) were estimated using a Cox proportional hazards model. During the follow-up, 219 first-ever CVD events were observed. The risk of CVD increased significantly with elevating ANGPTL2 levels after adjustment for age, sex, serum total cholesterol, use of lipid-lowering agents, ECG abnormalities, smoking habits, alcohol intake, and regular exercise (hazards ratios [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.27 [0.80–2.04]; Q3, 1.48 [0.95–2.32]; and Q4, 1.85 [1.20–2.85]; P=0.003 for trend). After additional adjustment for metabolic syndrome components and serum high-sensitivity C-reactive protein levels as an inflammatory marker, the association was attenuated but remained significant (hazards ratios [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.21 [0.76–1.94]; Q3, 1.38 [0.87–2.17]; and Q4, 1.66 [1.05–2.60]; P=0.02 for trend). Conclusions—Our findings suggest that elevated serum ANGPTL2 levels are a novel risk factor for the development of CVD in the general population. This association is partially mediated by metabolic disorders and inflammation.

Association Between Daily Sleep Duration and Risk of Dementia and Mortality in a Japanese Community: SLEEP AND RISK OF DEMENTIA AND DEATH

To investigate the association between daily sleep duration and risk of dementia and death in a Japanese elderly population.

Albuminuria increases the risks for both Alzheimer disease and vascular dementia in community-dwelling Japanese elderly: The hisayama study

Background Epidemiologic evidence has emerged to reveal an association of albuminuria and low estimated glomerular filtration rate (eGFR) with dementia, but the findings are inconsistent. In addition, there are limited studies addressing the association between albuminuria and Alzheimer disease (AD). Methods and Results A total of 1562 community‐dwelling Japanese subjects aged ≥60 years without dementia were followed up for 10 years. The outcomes were incidence of all‐cause dementia and its subtypes, namely, AD and vascular dementia (VaD). The hazard ratios for the outcomes were estimated according to urine albumin–creatinine ratio (UACR) and eGFR levels using a Cox proportional hazards model. During the follow‐up, 358 subjects developed all‐cause dementia (238 AD and 93 VaD). Higher UACR level was significantly associated with greater multivariable‐adjusted risks of all‐cause dementia (hazard ratios [95% confidence intervals]: 1.00 [reference], 1.12 [0.78–1.60], 1.65 [1.18–2.30], and 1.56 [1.11–2.19] for UACR of ≤6.9, 7.0–12.7, 12.8–29.9, and ≥30.0 mg/g, respectively), AD (1.00 [reference], 1.20 [0.77–1.86], 1.75 [1.16–2.64], and 1.58 [1.03–2.41], respectively), and VaD (1.00 [reference], 1.03 [0.46–2.29], 1.94 [0.96–3.95], and 2.19 [1.09–4.38], respectively). On the other hand, lower eGFR level was marginally associated with greater risk of VaD, but not AD. Subjects with UACR ≥12.8 mg/g and eGFR of <60 mL/min per 1.73 m2 had 3.3‐fold greater risk of VaD than those with UACR <12.8 mg/g and eGFR of ≥60 mL/min per 1.73 m2. Conclusions Albuminuria is a significant risk factor for the development of both AD and VaD in community‐dwelling Japanese elderly. Moreover, albuminuria and low eGFR are mutually associated with a greater risk of VaD.

Patterns and Levels of Sedentary Behavior and Physical Activity in a General Japanese Population: The Hisayama Study

Background The purpose of this cross-sectional study was to describe the patterns and levels of sedentary time and physical activity (PA) in a general Japanese population. Methods A total of 1,740 community-dwelling Japanese adults aged ≥40 years participated in this study. Sedentary time and PA were assessed for 7 consecutive days using a tri-axial accelerometer. Daily patterns and levels of sedentary time and PA were calculated by sex, age group (40–64, 65–74, and ≥75 years), and body mass index (BMI; <25 and ≥25 kg/m2). Results Participants spent half of their waking time being sedentary, 32.7% of which was accumulated in prolonged bouts ≥30 minutes, versus only 54.4 minutes/day (7% of waking time) as moderate-to-vigorous PA (MVPA) (11.8 minutes/day in bouts ≥10 minutes). In addition to total sedentary time, men had longer prolonged sedentary bouts and fewer breaks per sedentary hour than women. Similar trends were observed in participants aged ≥75 years and those with a higher BMI (≥25 kg/m2) compared to those with a younger age and lower BMI. Moreover, participants aged ≥75 years and those with a higher BMI accumulated fewer MVPA minutes in bouts ≥10 minutes. Only 34.8% of the population met the recommended level of ≥150 minutes/week MVPA in bouts ≥10 minutes. Conclusion Japanese adults accumulated a large proportion of total sedentary time in prolonged bouts but few minutes in sustained bouts of MVPA, and few of them met the current PA guideline.

Association between the ratio of serum arachidonic acid to eicosapentaenoic acid and the presence of depressive symptoms in a general Japanese population: the Hisayama Study

BACKGROUND Epidemiological evidence suggests that fish consumption and intake of n-3 polyunsaturated fatty acids (PUFA)-namely, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)-confer protection against depression. However, few studies have addressed the influence of the balance between n-3 PUFA and n-6 PUFA in the human body on depression. METHODS A total of 2,529 community-dwelling Japanese residents aged ≥ 40 years were assessed for depressive symptoms (defined as a score of 16 points or more on the Center for Epidemiologic Studies Depression Scale [CES-D]) in 2007. The serum arachidonic acid (AA) /EPA ratio and AA/DHA ratio were measured in frozen samples collected in 2002 and categorized into quartiles. The odds ratios (ORs) for the presence of depressive symptoms were calculated using a logistic regression model. RESULTS The prevalence of depressive symptoms was 4.3%. There was no significant association between either the serum AA/EPA ratio or AA/DHA ratio and the presence of depressive symptoms. However, subjects with the highest serum AA/EPA ratios (range: 3.28-13.3) had a 4.10 times (95%CI: 1.13-19.80) greater OR for the presence of depressive symptoms than those with the lowest ratios (0.30-1.65) after adjusting for confounding factors in the subgroup with high-sensitivity C-reactive protein (hs-CRP) ≥ 1.0 mg/L, while no clear association was observed in the subgroup with hs-CRP < 1.0 mg/L. LIMITATIONS Reverse causality is possible due to the cross-sectional study design. CONCLUSIONS Our findings suggest that a higher serum AA/EPA ratio is associated with a greater likelihood of depressive symptoms in subjects with systemic inflammation in the general Japanese population.

A potential novel pathological implication of serum soluble triggering receptor expressed on myeloid cell 2 in insulin resistance in a general Japanese population: the Hisayama Study

AIMS No cohort study has examined the pathological significance of triggering receptor expressed on myeloid cell 2 (TREM2), a cell surface receptor expressed on myeloid lineage cells, and its soluble form, sTREM2, in insulin resistance in a general population. METHODS A total of 2742 community-dwelling Japanese individuals aged ≥40 years were divided into 4 groups according to the serum sTREM2 concentration quartiles. We examined the cross-sectional association of sTREM2 levels with anthropometric parameters and the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS The median sTREM2 concentrations was 255.6 (interquartile range, 162.5-419.2) pg/mL. In multivariate analyses, waist circumference and fat mass index increased with elevating sTREM2 levels (P for trend: <0.001 and 0.02, respectively), but there was no significant association between sTREM2 levels and body mass index and fat-free mass index. Among the subjects without taking antidiabetic medications (n = 2610), greater sTREM2 levels were associated with higher HOMA-IR (P for trend <0.001) even after adjusting for waist circumference, fat mass index, and high-sensitivity C-reactive protein. CONCLUSIONS Our findings suggest that serum sTREM2 had novel pathological roles in insulin resistance, while obesity and inflammation had no substantial effects on the relationship between sTREM2 and insulin resistance in this cohort.

Development and validation of modified risk prediction models for cardiovascular disease and its subtypes: The Hisayama Study

BACKGROUND AND AIMS Predicting cardiovascular events is of practical benefit for disease prevention. The aim of this study was to develop and evaluate an updated risk prediction model for cardiovascular diseases and its subtypes. METHODS A total of 2462 community residents aged 40-84 years were followed up for 24 years. A Cox proportional hazards regression model was used to develop risk prediction models for cardiovascular diseases, and separately for stroke and coronary heart diseases. The risk assessment ability of the developed model was evaluated, and a bootstrapping method was used for internal validation. The predicted risk was translated into a simplified scoring system. A decision curve analysis was used to evaluate clinical usefulness. RESULTS The multivariable model for cardiovascular diseases included age, sex, systolic blood pressure, hemoglobin A1c, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, smoking habits, and regular exercise as predictors. The models for stroke and coronary heart diseases incorporated both shared and unique variables. The developed models showed good discrimination with little evidence of overfitting (optimism-corrected Harrells C statistics 0.726-0.777) and calibrations (Hosmer-Lemeshow test, p = 0.44-0.90). The decision curve analysis revealed that the predicted risk-based decision-making would have higher net benefit than either a CVD intervention strategy for all individuals or no individuals. CONCLUSIONS The developed risk prediction models showed a good performance and satisfactory internal validity, which may help understand individual risk and setting personalized goals, and promote risk stratification in public health strategies for CVD prevention.