Skin carotenoid scores and metabolic syndrome in a general Japanese population: the Hisayama study.

BACKGROUND: Higher vegetable intake is being promoted as an initiative to prevent lifestyle-related diseases. Carotenoids are yellow or red pigment components and are widely present in vegetables. Since ingested carotenoids accumulate in the skin, skin carotenoid levels are a quantitative indicator of vegetable intake. Recently, noninvasive optical sensors for assessing skin carotenoid levels were developed. We here examined the association between skin carotenoid scores measured using optical sensors and the presence of metabolic syndrome. METHODS: A total of 1618 individuals (604 men and 1014 women) aged ≥ 40 years (mean age 63.1 years) participated in the study. Skin carotenoid scores were determined using a noninvasive optical sensor based on multiple spatially resolved reflectance spectroscopy. Metabolic syndrome was defined based on the Joint Scientific Statement criteria developed by six international scientific societies. Multivariable-adjusted logistic regression models were used. RESULTS: The prevalence of metabolic syndrome was 31.3% (n = 506). A remarkably strong association was found between higher skin carotenoid scores and lower prevalence of metabolic syndrome after adjusting for confounders. The multivariable-adjusted odds ratio for the presence of metabolic syndrome in individuals with the highest quartile of skin carotenoid scores was 0.39 (95% confidence interval, 0.28-0.55) compared to those with the lowest quartile. CONCLUSIONS: Our findings suggest that higher skin carotenoid scores measured by non-invasive optimal sensors are significantly associated with a lower likelihood of having metabolic syndrome in the general Japanese population.

Association between retinopathy and risk of dementia in a general Japanese population: the Hisayama Study.

We investigated the association of retinopathy with the risk of dementia in a general older Japanese population. A total of 1709 population-based residents aged 60 years or older without dementia were followed prospectively for 10 years (2007-2017). They underwent color fundus photography in 2007. Retinopathy was graded according to the Modified Airlie House Classification. Main outcome was the Incidence of dementia. A Cox proportional hazards model was used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) for the risk of dementia by the presence of retinopathy. During the follow-up period, 374 participants developed all-cause dementia. The cumulative incidence of dementia was significantly higher in those with retinopathy than those without (p < 0.05). Individuals with retinopathy had significantly higher risk of developing dementia than those without after adjustment for potential confounding factors (HR 1.64, 95% CI 1.19-2.25). Regarding the components of retinopathy, the presence of microaneurysms was significantly associated with a higher multivariable-adjusted HR for incident dementia (HR 1.94, 95% CI 1.37-2.74). Our findings suggest that, in addition to systemic risk factors, retinal microvascular signs from fundus photography provide valuable information for estimating the risk of developing dementia.

Plasma biomarkers for predicting the development of dementia in a community-dwelling older Japanese population.

AIM: To assess the association between plasma amyloid ß (Aß) 42/40, phosphorylated tau (p-τ)181, glial fibrillary acidic protein (GFAP), or neurofilament light chain (NfL) and the risk of dementia and to determine whether these plasma biomarkers could improve the ability to predict incident dementia in a general older population. METHODS: A total of 1346 Japanese community-dwelling individuals aged ≥65 years without dementia were followed prospectively for 5.0 years. Plasma biomarkers were quantified using a Simoa HD-X analyzer. A Cox proportional hazards model was used to estimate the hazard ratios of each plasma biomarker level for the risk of dementia. RESULTS: During the follow-up, 151 participants developed dementia, of whom 108 had Alzheimer disease (AD) and 43 non-Alzheimer dementia (non-AD). Lower plasma Aß42/40 levels and higher plasma p-τ181 levels were significantly associated with developing AD but not non-AD, whereas significant associations were observed between higher plasma levels of GFAP and NfL and risk of both AD and non-AD (all P for trend <0.05). In addition, adding these four plasma biomarkers into a model consisting of the total score of the dementia risk model significantly improved the predictive ability for incident dementia. CONCLUSION: Our findings suggest that plasma Aß42/40 and p-τ181 are specific markers of AD, and plasma GFAP and NfL are potential biomarkers for all-cause dementia in the general Japanese older population. In addition, the measurement of these plasma biomarkers may be a useful and relatively low-invasive procedure for identifying individuals at high risk for developing dementia in clinical practice.

Serum high-sensitivity C-reactive protein and dementia in a community-dwelling Japanese older population (JPSC-AD).

In recent years, the association between neuroinflammatory markers and dementia, especially Alzheimer's disease (AD), has attracted much attention. However, the evidence for the relationship between serum-hs-CRP and dementia including AD are inconsistent. Therefore, the relationships of serum high-sensitivity CRP (hs-CRP) with dementia including AD and with regions of interest of brain MRI were investigated. A total of 11,957 community residents aged 65 years or older were recruited in eight sites in Japan (JPSC-AD Study). After applying exclusion criteria, 10,085 participants who underwent blood tests and health-related examinations were analyzed. Then, serum hs-CRP levels were classified according to clinical cutoff values, and odds ratios for the presence of all-cause dementia and its subtypes were calculated for each serum hs-CRP level. In addition, the association between serum hs-CRP and brain volume regions of interest was also examined using analysis of covariance with data from 8614 individuals in the same cohort who underwent brain MRI. After multivariable adjustment, the odds ratios (ORs) for all-cause dementia were 1.04 (95% confidence interval [CI] 0.76-1.43), 1.68 (95%CI 1.08-2.61), and 1.51 (95%CI 1.08-2.11) for 1.0-1.9 mg/L, 2.0-2.9 mg/L, and ≥ 3.0 mg/L, respectively, compared to < 1.0 mg/L, and those for AD were 0.72 (95%CI 0.48-1.08), 1.76 (95%CI 1.08-2.89), and 1.61 (95%CI 1.11-2.35), for 1.0-1.9 mg/L, 2.0-2.9 mg/L, and ≥ 3.0 mg/L, respectively, compared to < 1.0 mg/L. Multivariable-adjusted ORs for all-cause dementia and for AD prevalence increased significantly with increasing serum hs-CRP levels (p for trend < 0.001 and p = 0.001, respectively). In addition, the multivariable-adjusted temporal cortex volume/estimated total intracranial volume ratio decreased significantly with increasing serum hs-CRP levels (< 1.0 mg/L 4.28%, 1.0-1.9 mg/L 4.27%, 2.0-2.9 mg/L 4.29%, ≥ 3.0 mg/L 4.21%; p for trend = 0.004). This study's results suggest that elevated serum hs-CRP levels are associated with greater risk of presence of dementia, especially AD, and of temporal cortex atrophy in a community-dwelling Japanese older population.

Association Between Serum NT-proBNP and Gray Matter Atrophy Patterns in an Older Japanese Population: The Hisayama Study.

Several population-based studies have reported that higher serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are associated with brain morphological changes. However, no population-based studies have examined the relationship between serum NT-proBNP and various regional brain volumes in detail. We here analyzed the brain MRI data of 1 201 community-dwelling Japanese aged ≥65 years. Regional gray matter volumes (GMV) and intracranial volume (ICV) were estimated by applying voxel-based morphometry (VBM) methods. The associations of serum NT-proBNP with regional GMV/ICV were examined by analysis of covariance. The regional gray matter atrophy patterns associated with elevated serum NT-proBNP levels were investigated using VBM without a priori regions of interest. The multivariable-adjusted means of the frontal, temporal, hippocampal, parahippocampal, and entorhinal GMV/ICV decreased significantly with elevated serum NT-proBNP levels (all p for trend and q values of false discovery rate correction < .05). In VBM, elevated serum NT-proBNP levels were correlated with atrophy of the bilateral hippocampi, bilateral amygdalas, bilateral parahippocampal gyri, bilateral entorhinal areas, bilateral fusiform gyri, left middle temporal gyrus, left inferior temporal gyrus, right central operculum, right posterior orbital gyrus, bilateral middle frontal gyri, anterior cingulate gyrus and bilateral medial frontal cortices. In a sensitivity analysis excluding 254 participants with mild cognitive impairment or dementia, serum NT-proBNP levels were correlated with atrophy of the bilateral hippocampi, bilateral amygdalas, bilateral parahippocampal gyri, bilateral fusiform gyri, and left middle frontal gyrus. Our data suggest that elevated serum NT-proBNP levels are associated with gray matter atrophy in brain regions that play an important role in cognitive function.

Day-to-day home blood pressure variability and risk of atrial fibrillation in a general Japanese population: the Hisayama Study.

AIMS: Several prospective studies have reported that higher visit-to-visit blood pressure variability (BPV) is associated with atrial fibrillation (AF). However, no studies have investigated the association between day-to-day BPV assessed by home blood pressure measurement and the development of AF. METHODS: A total of 2,827 community-dwelling Japanese aged ≥40 years without prior AF were followed up for 10 years (2007-2017). Day-to-day home BPV (defined as coefficients of variation [CoV] of home systolic blood pressure [SBP] for 28 days) were categorized into 4 groups according to the quartiles: Q1, ≤4.64%; Q2, 4.65%-5.70%; Q3, 5.71%-7.01%; Q4, ≥7.02%. The hazard ratios for developing AF were estimated using a Cox proportional hazards model. RESULTS: During the follow-up period, 134 participants developed new-onset AF. The crude incidence rates of AF increased significantly with higher CoV levels of home SBP: 2.1, 4.7, 5.3, and 8.8 per 1000 person-years in the first, second, third, and fourth quartiles, respectively (P for trend <0.01). After adjusting for potential confounders, increased CoV levels of home SBP were associated significantly with a higher risk of AF (P for trend =0.02). The participants in the highest quartile of CoV had a 2.18-fold (95% confidence intervals: 1.18-4.04) increased risk of developing AF compared to those in the lowest quartile. CONCLUSIONS: The present findings suggest that increased day-to-day home BPV levels are associated with a higher risk of the development of AF in a general Japanese population.

This prospective cohort study of a general Japanese population demonstrated a significant association between higher day-to-day blood pressure variability (BPV) assessed by home blood pressure monitoring and risk for the development of atrial fibrillation (AF). In addition, the association between BPV and the development of AF tended to be stronger in participants without hypertension.The findings of this study indicate that the evaluation of day-to-day BPV with home blood pressure monitoring may be useful to assess future risk of AF in participants with and without hypertension, and treatment that takes into account day-to-day BPV in addition to other cardiovascular risk factors may be necessary to prevent the development of AF.

Autonomic nervous system function assessed by heart rate variability and the presence of symptoms affecting activities of daily living in community-dwelling residents with chronic pain: The Hisayama Study.

BACKGROUND: Autonomic nervous system dysfunction has been reported to be associated with impaired activities of daily living (ADL) among patients with chronic pain, but the association has not been fully addressed in general populations. This study cross-sectionally investigated the association between autonomic nervous system function and the presence of subjective symptoms affecting ADL in community-dwelling residents with chronic pain. METHODS: A total of 888 residents with chronic pain, aged 40-79 years, who underwent a health examination in 2017-2018 were included. Based on heart rate variability measured by fingertip pulse wave, the standard deviation of normal-to-normal intervals (SDNN), root mean square of successive RR interval differences (RMSSD), low frequency (LF) power, and high frequency (HF) power were calculated. Symptoms affecting ADL were defined as those scoring ≥1 on the modified Rankin Scale. Odds ratios (ORs) and their 95% confidence intervals (CIs) for symptoms affecting ADL were estimated using a logistic regression analysis. RESULTS: The overall prevalence of symptoms affecting ADL was 39.4%. The ORs for symptoms affecting ADL increased significantly per 1-standard-deviation decrement in log-transformed SDNN (OR 1.23 [95% CI 1.06-1.44]), RMSSD (1.25 [1.08-1.45]), LF power (1.29 [1.11-1.52]), and HF power (1.29 [1.11-1.51]) after adjusting for age, sex, education, hypertension, diabetes, serum total cholesterol level, body mass index, past medical history, current smoking, current drinking, exercise, depressive symptoms, and pain intensity. CONCLUSIONS: Decreased heart rate variability was associated with the presence of symptoms affecting ADL among individuals with chronic pain in a Japanese community. SIGNIFICANCE: Decrease in heart rate variability was associated with the presence of symptoms affecting ADL among individuals with chronic pain in a Japanese community. This article could help scientists understand the significance of autonomic nervous system dysfunction in the pathology of chronic pain. Approaches that target autonomic nervous system dysfunction may be an option to relieve or prevent symptoms affecting ADL for chronic pain sufferers.

The relation between vaccination status and referral to a consultation-liaison psychiatry service for hospitalized patients with COVID-19.

BACKGROUND: Previous studies have shown that patients with Coronavirus Disease 2019 (COVID-19) are likely to be affected by delirium and other psychiatric complications. We aimed to evaluate the relation between COVID-19 vaccination status and referral of patients hospitalized with COVID-19 for consultation-liaison psychiatry services. METHOD: From the medical records used for this retrospective, single hospital-based study, 576 patients were identified who were over 18 years-of-age and hospitalized with a diagnosis of COVID-19 between March 2020 and March 2022. The data of 531 for whom the vaccine history was obtained from the medical records were available for analysis: 455 without and 76 with referral to consultation-liaison psychiatry. A history of COVID-19 vaccination at least two times was used in the analysis of the odds for referral to liaison psychiatric consultation: 95% confidence interval (CI) in multivariable logistic regression. The adjustment factors included sex, age, body mass index (BMI), severity of COVID-19, C-reactive protein level, medical history, and therapeutic factors such as the use of remdesivir, steroids, or mechanical ventilation. RESULTS: The prevalence of psychiatric consultation was 14.3%. Patients without vaccination had a 7-times greater OR (95%CI:2.08-23.58) than vaccinated patients for a referral for consultation-liaison psychiatry services after adjusting for confounding factors. CONCLUSION: Non-vaccination was associated with a greater likelihood of referral for consultation-liaison psychiatry service among these hospitalized Japanese patients with COVID-19, even after adjusting for clinical and therapeutic factors. It is possible that vaccination greatly lessens the need for the referral of COVID-19 patients for consultation-liaison psychiatry services.

Inadequate care and excessive overprotection during childhood are associated with the presence of diabetes mellitus in adulthood in a general Japanese population: a cross-sectional analysis from the Hisayama Study.

OBJECTIVE: To investigate associations between parenting styles during childhood and diabetes in adulthood in a Japanese community. METHODS: In 2011, 710 community-dwelling Japanese residents aged ≥ 40 years were assessed for the presence of diabetes and for their perceptions of the parenting style of their parents, as measured using the "care" and "overprotection" scales of the Parental Bonding Instrument. Care and overprotection scores for each parent were dichotomized by age-specific median values. Diabetes mellitus was defined as a fasting plasma glucose level of ≥ 7.0 mmol/L, a 2-h post-loaded glucose level of ≥ 11.1 mmol/L, HbA1c ≥ 6.5%, and/or the current use of insulin or oral glucose-lowering agents. The odds ratios (ORs) for prevalent diabetes were calculated using a logistic regression model. RESULTS: The prevalence of diabetes was 14.9%. Subjects with a high paternal overprotection score had a significantly greater likelihood of prevalent diabetes than those with a low paternal overprotection score after adjusting for confounders (OR 1.71, 95% confidence interval [CI] 1.06-2.77), while there was no significant association between paternal care and diabetes. Additionally, the multivariable-adjusted ORs for the presence of diabetes were significantly higher in subjects with a low maternal care score (OR 1.61, 95%CI 1.00-2.60) or in subjects with a high maternal overprotection score (OR 1.73, 95%CI 1.08-2.80). Moreover, the subjects with a low care score and high overprotection score for both their father and mother had a significantly higher multivariable-adjusted OR of diabetes than those with a high care score and low overprotection score for both parents (OR 2,12, 95%CI 1.14-3.95). CONCLUSIONS: This study suggests that inadequate care and excessive overprotection during childhood may contribute to the development of diabetes in adulthood.

Gender and age influence the association between gait speed and mild cognitive impairment in community-dwelling Japanese older adults: from the Japan Prospective Studies Collaboration for Ageing and Dementia (JPSC-AD).

BACKGROUND: Studies have shown that decreased gait speed is associated with impaired cognitive function. However, whether this association is equivalent across ages or genders in the older population remains unclear. Thus, we examined the association between mild cognitive impairment (MCI) and gait speed emphasising the influence of age and gender. METHODS: Overall, 8233 Japanese participants aged ≥65 years were enrolled in this cross-sectional study between 2016 and 2018. After stratification by gender and age group, the participants' gait speeds were divided into quintiles, and the difference in MCI prevalence at each gait speed quintile was calculated. Logistic regression analyses were performed to assess the odds of MCI for each quintile and to assess the influence of age and gender. RESULTS: Males had a consistently higher prevalence of MCI than females. The odds of MCI were increased as gait speed decreased. Logistic regression analyses revealed that in the multivariable-adjusted model 2, the odds ratios (95% confidence interval; CI) for MCI were 2.02 (1.47-2.76) for females and 1.75 (1.29-2.38) for males in the slowest gait speed quintiles compared to the fastest quintile. In the stratified analyses, only males showed an age-dependent increase in the associations between gait speed and MCI, while females exhibited comparable associations across age groups. CONCLUSIONS: Reduced gait speed was associated with increased odds of MCI, and this association may vary according to gender and age. Therefore, gait speed could serve as a valuable screening tool for MCI, with gender- and age-dependent clinical implications.

Association Between Frequency of Social Contact and Brain Atrophy in Community-Dwelling Older People Without Dementia: The JPSC-AD Study.

BACKGROUND AND OBJECTIVES: Epidemiologic evidence has shown that social isolation, a low frequency of social contact with others, is associated with the risk of dementia and late-life depressive symptoms. Therefore, we hypothesized that low frequency of social contact may be involved in brain atrophy, and depressive symptoms may play some role in this relationship. We aimed to evaluate the association between low frequency of social contact and the volumes of various brain regions and to assess the extent to which depressive symptoms mediate these relationships from a large population-based multisite cohort study. METHODS: Dementia-free community-dwelling Japanese aged 65 years or older underwent brain MRI scans and a comprehensive health examination. Frequency of contact with noncohabiting relatives and friends was determined by asking a single question with 4 categories: everyday, several times a week, several times a month, and seldom. Total and regional brain volumes, intracranial volume (ICV), and white matter lesion volume were estimated using FreeSurfer software. The associations between frequency of social contact and brain volumes per ICV were examined using analyses of covariance. Mediation analyses were conducted to calculate the proportion of the associations explained by depressive symptoms. RESULTS: We included 8,896 participants. The multivariable-adjusted mean of the total brain volume in the group with the lowest frequency of social contact was significantly lower compared with that in the group with the highest frequency of social contact (67.3% vs 67.8%), with a significant increasing trend across the groups (p value for trend <0.001). The white matter lesion volume increased significantly with lower frequency of social contact (0.30% in the lowest frequency group vs 0.26% in the highest frequency group, p value for trend <0.001). Lower frequency of social contact was associated with smaller volumes in the temporal lobe, occipital lobe, cingulum, hippocampus, and amygdala (all q values of false discovery rate correction <0.05). The relationships seemed to be partly mediated by depressive symptoms, which accounted for 15%-29% of the observed associations. DISCUSSION: Lower frequency of social contact was associated with decreased total and cognitive function-related regional brain volumes. In addition, depressive symptoms partially explained the association in community-dwelling older people without dementia in Japan.

CKD, Brain Atrophy, and White Matter Lesion Volume: The Japan Prospective Studies Collaboration for Aging and Dementia.

Rationale & Objective: Chronic kidney disease, defined by albuminuria and/or reduced estimated glomerular filtration rate (eGFR), has been reported to be associated with brain atrophy and/or higher white matter lesion volume (WMLV), but there are few large-scale population-based studies assessing this issue. This study aimed to examine the associations between the urinary albumin-creatinine ratio (UACR) and eGFR levels and brain atrophy and WMLV in a large-scale community-dwelling older population of Japanese. Study Design: Population-based cross-sectional study. Setting & Participants: A total of 8,630 dementia-free community-dwelling Japanese aged greater than or equal to 65 years underwent brain magnetic resonance imaging scanning and screening examination of health status in 2016-2018. Exposures: UACR and eGFR levels. Outcomes: The total brain volume (TBV)-to-intracranial volume (ICV) ratio (TBV/ICV), the regional brain volume-to-TBV ratio, and the WMLV-to-ICV ratio (WMLV/ICV). Analytical Approach: The associations of UACR and eGFR levels with the TBV/ICV, the regional brain volume-to-TBV ratio, and the WMLV/ICV were assessed by using an analysis of covariance. Results: Higher UACR levels were significantly associated with lower TBV/ICV and higher geometric mean values of the WMLV/ICV (P for trend = 0.009 and <0.001, respectively). Lower eGFR levels were significantly associated with lower TBV/ICV, but not clearly associated with WMLV/ICV. In addition, higher UACR levels, but not lower eGFR, were significantly associated with lower temporal cortex volume-to-TBV ratio and lower hippocampal volume-to-TBV ratio. Limitations: Cross-sectional study, misclassification of UACR or eGFR levels, generalizability to other ethnicities and younger populations, and residual confounding factors. Conclusions: The present study demonstrated that higher UACR was associated with brain atrophy, especially in the temporal cortex and hippocampus, and with increased WMLV. These findings suggest that chronic kidney disease is involved in the progression of morphologic brain changes associated with cognitive impairment.

Serum Mac-2 Binding Protein Glycosylation Isomer Concentrations Are Associated With Incidence of Type 2 Diabetes.

CONTEXT: Serum Mac-2 binding protein glycosylation isomer (M2BPGi) concentrations are known to be an indicator of chronic liver injury and fibrosis. OBJECTIVE: This study aimed to investigate the association between serum M2BPGi concentrations and the development of type 2 diabetes in a Japanese community. METHODS: A total of 2143 community-dwelling Japanese individuals aged 40-79 years without diabetes at baseline were followed up for 7 years. Serum M2BPGi concentrations were divided into quintiles: Q1, ≤0.37 cutoff index (COI); Q2, 0.38-0.49 COI; Q3, 0.50-0.62 COI; Q4, 0.62-0.80 COI; and Q5, ≥0.81 COI. Cox proportional hazards models were used to estimate hazard ratios and 95% CIs for the development of type 2 diabetes. RESULTS: During the follow-up period, 219 individuals developed type 2 diabetes. The age- and sex-adjusted cumulative incidence of type 2 diabetes significantly increased with elevating serum M2BPGi levels (P for trend < .01). This association remained significant after adjustment for potential confounders (P for trend = .04). This significant association attenuated to a nonsignificant level after additionally adjusting for serum high-sensitivity C-reactive protein or homeostasis model assessment of insulin resistance. CONCLUSION: The present study demonstrated that higher serum M2BPGi concentrations were significantly associated with higher risk of diabetes in a Japanese community. Moreover, inflammation and insulin resistance were suggested to contribute to the excess risk of diabetes in individuals with higher serum M2BPGi levels. These findings shed light on the importance of inflammation and insulin resistance when considering the pathogenesis of diabetes.

Association of white matter lesions and brain atrophy with the development of dementia in a community: the Hisayama Study.

AIM: To investigate the association of white matter lesions volume (WMLV) levels with dementia risk and the association between dementia risk and the combined measures of WMLV and either total brain atrophy or dementia-related gray matter atrophy in a general older population. METHODS: One thousand one hundred fifty-eight Japanese dementia-free community-residents aged ≥65 years who underwent brain magnetic resonance imaging were followed for 5.0 years. WMLV were segmented using the Lesion Segmentation Toolbox. Total brain volume (TBV) and regional gray matter volume were estimated by voxel-based morphometry. The WMLV-to-intracranial brain volume ratio (WMLV/ICV) was calculated, and its association with dementia risk was estimated using Cox proportional hazard models. Total brain atrophy, defined as the TBV-to-ICV ratio (TBV/ICV), and dementia-related regional brain atrophy defined based on our previous report were calculated. The association between dementia risk and the combined measures of WMLV/ICV and either total brain atrophy or the number of atrophied regions was also tested. RESULTS: During the follow-up, 113 participants developed dementia. The risks of dementia increased significantly with higher WMLV/ICV levels. In addition, dementia risk increased additively both in participants with higher WMLV/ICV levels and lower TBV/ICV levels and in those with higher WMLV/ICV levels and a higher number of dementia-related brain regional atrophy. CONCLUSION: The risk of dementia increased significantly with higher WMLV/ICV levels. An additive increment in dementia risk was observed with higher WMLV/ICV levels and lower TBV/ICV levels or a higher number of dementia-related brain regional atrophy, suggesting the importance of prevention or control of cardiovascular risk factors.

Changes in the Eicosapentaenoic Acid to Arachidonic Acid Ratio in Serum over 10 Years in a Japanese Community: The Hisayama Study.

AIM: Circulating omega-3 and omega-6 polyunsaturated fatty acids may to contribute to cardiovascular health at the population level. Over a decade, we investigated changes in the serum eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio, and in serum concentrations of the individual fatty acids, in a Japanese community. METHODS: Community surveys took place in 2002-2003 and 2012-2013 in a rural area of Japan. The community surveys included 3,194 and 3,220 community dwellers aged ≥ 40 years who did not take EPA medication in 2002-2003 and 2012-2013, respectively. Fatty acid fractionations in serum were measured using a gas chromatography method. Changes in the serum EPA/AA ratio over time were examined using linear mixed models. RESULTS: Overall, the average serum EPA/AA ratio decreased over the 10 years. A decreasing trend in the serum EPA/AA ratio occurred in all age groups except participants aged ≥ 80 years, with larger decreases in the younger age groups. A similar decline in serum EPA/AA ratio occurred in participants with and those without lipid-lowering therapy. Serum EPA concentrations were slightly increased in the whole population but remained stable or even decreased in participants aged 40-69. In contrast, the average serum AA concentrations increased in all age groups. CONCLUSION: In a Japanese community, the serum EPA/AA ratio decreased over 10 years at the population level, especially in middle-aged participants.

Association of gait speed with regional brain volumes and risk of dementia in older Japanese: The Hisayama study.

BACKGROUND: To investigate the association of gait speed with regional brain volumes and the risk of incident dementia. METHODS: A total of 1112 dementia-free Japanese residents aged ≥65 years who underwent brain magnetic resonance imaging were followed for 5.0 years (median). The participants were classified into the age- and sex-specific quartile levels of maximum gait speed. Regional gray matter volumes (GMV) and white matter hyperintensities volumes (WMHV) were measured by applying voxel-based morphometry methods. The cross-sectional association of maximum gait speed with regional GMV was examined using an analysis of covariance. We also estimated the association between maximum gait speed level and the risk of developing dementia using a Cox proportional hazards model. Mediation analyses were conducted to determine the contribution of regional brain volumes to the association between maximum gait speed and dementia. RESULTS: Lower maximum gait speed was significantly associated with lower GMV of the total brain, frontal lobe, temporal lobe, cingulate gyrus, insula, hippocampus, amygdala, basal ganglia, thalamus, and cerebellum, and increased WMHV at baseline. During the follow-up, 108 participants developed dementia. The incidence rate of all dementias increased significantly with decreasing maximum gait speed after adjusting for potential confounders (P for trend = 0.03). The mediating effects of the GMV of the hippocampus, GMV of the insula, and WMHV were significant. CONCLUSIONS: Lower maximum gait speed was significantly associated with an increased risk of dementia. Reduced GMV of the hippocampus or insula, and an increase in WMHV was likely to be involved in this association.

Family dysfunction is associated with chronic pain in a community-dwelling Japanese population: The Hisayama study.

BACKGROUND: Poor family functioning has been reported to be associated with the severity of chronic pain in outpatients, but the association has not been fully addressed in general populations. The present study aimed to examine the association between family dysfunction levels and the presence of chronic pain in a community-dwelling Japanese population. METHODS: A total of 2598 participants aged ≥40 years were classified as having healthy, borderline or unhealthy family functioning. Chronic pain was defined as subjective pain for three months or longer, and further classified by pain intensity, the number of chronic pain sites, pain duration and the extent of pain spread. A logistic regression model was used to compute the odds ratios (ORs) for chronic pain outcomes. RESULTS: The prevalence of chronic pain was 49%. The age- and sex-adjusted prevalence of total and severe chronic pain were increased significantly with increasing family dysfunction levels (all p for trend <0.01). After adjusting for sociodemographic, physical, social and family structure factors, the ORs (95% confidence intervals [CI]) for having chronic pain among borderline and unhealthy groups were 1.20 (1.01-1.44) and 1.43 (1.15-1.79), respectively, as compared with a healthy family function group. The association was stronger among people who were employed and those who were living with their children. In addition, the ORs for severe chronic pain increased significantly with increasing levels of family dysfunction. CONCLUSIONS: The family dysfunction level was positively associated with the presence as well as the severity of chronic pain in a community-dwelling population. SIGNIFICANCE: A biopsychosocial burden due to family relationships could worsen the clinical presentation of pain. Social support or family therapy for dysfunctional families would be a potential initiative for the prevention or management of chronic pain.

Association of Inner Retinal Thickness with Prevalent Dementia and Brain Atrophy in a General Older Population: The Hisayama Study.

Purpose: To assess the association of inner retinal thickness with prevalent dementia and regional brain atrophy in a general older population of Japanese. Design: Population-based, cross-sectional study. Participants: A total of 1078 residents aged 65 years or older who participated in an eye examination, a comprehensive survey of dementia, and brain magnetic resonance imaging scanning in 2017. Methods: The thicknesses of the inner retinal layers, namely, the ganglion cell-inner plexiform layer (GC-IPL) and retinal nerve fiber layer (RNFL)-were measured by swept-source OCT (SS-OCT). The association of these retinal thicknesses with the risk of the presence of dementia was estimated using restricted cubic splines and logistic regression models. Regional brain volumes were estimated separately by applying 2 different methods: voxel-based morphometry (VBM) and analysis by FreeSurfer software. The associations of GC-IPL and RNFL thickness with each brain regional volume were analyzed using multiple regression analysis. Main Outcome Measure: Prevalent dementia and regional brain atrophy. Results: Among the study participants, 61 participants (5.7%) were diagnosed with dementia. The likelihood of the presence of dementia significantly increased with lower GC-IPL thickness after adjusting for potential confounders (odds ratio, 1.62 [95% confidence interval, 1.30-2.01] per 1 standard deviation decrement in the GC-IPL thickness), but no significant association was observed with RNFL thickness. In the VBM analyses with the multivariable adjustment, lower GC-IPL thickness was significantly associated with lower volume of known brain regions related to cognitive functions (i.e., the hippocampus, amygdala, entorhinal area, and parahippocampal gyrus) and visual functions (i.e., the cuneus, lingual gyrus, and thalamus). Meanwhile, the volume of the thalamus significantly decreased with lower RNFL thickness, but none of the brain regions related to cognitive function exhibited a volume change in association with RNFL thickness. The sensitivity analysis using FreeSurfer analysis also showed that lower GC-IPL thickness was significantly associated with lower regional brain volume/intracranial volume of the hippocampus, amygdala, cuneus, lingual gyrus, and thalamus. Conclusions: Our findings suggest that the measurement of GC-IPL thickness by SS-OCT, which is a noninvasive, convenient, and reproducible method, might be useful for identifying high-risk individuals with dementia.