Change in the association between coffee intake and ischemic heart disease in an international ecological study from 1990 to 2018.

In previous observational studies, the association between coffee intake and risk of cardiovascular disease has reversed from positive to negative over time. This long-term international ecological study examined whether the association between coffee intake and mortality and incidence rates of ischemic heart disease (IHD) changed between 1990 and 2018 using multiple coherent data. We obtained data on coffee intake per capita, IHD mortality and incidence rates per 100,000 population, and socioeconomic and lifestyle indicators for each country from various publicly available databases. We integrated and analyzed data from 147 countries with populations of ≥ 1 million. We employed a linear mixed model analysis to assess the association between coffee intake and IHD mortality and incidence rates by year. The mean global coffee intake increased (p < 0.001), whereas IHD mortality (p < 0.001) and incidence (p = 0.073) decreased. In all models, the interaction between coffee intake and year showed a significant inverse association for IHD mortality and incidence rates (p < 0.001 for all). The country-level association between coffee intake and IHD mortality and incidence rates between 1990 and 2018 was stronger in the negative direction.

Green tea consumption is associated with annual changes in hippocampal volumes: A longitudinal study in community-dwelling middle-aged and older Japanese individuals.

BACKGROUND: To investigate the association between green tea consumption and the annual rate of change of gray matter (GM), white matter (WM), and hippocampal volumes in community-dwelling middle-aged and older Japanese individuals. METHODS: A prospective cohort study with two years of follow-up was conducted as part of the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) project. A total of 1693 participants (862 men and 831 women, aged 40-89 years) were included. Green tea consumption (mL/day) data were collected with a 3-day dietary record. Volumes of GM, WM, and the hippocampus were estimated by T1-weighted brain magnetic resonance imaging and FreeSurfer software. The GM ratio, WM ratio, and hippocampal ratio (HR) were calculated as the percentages of total intracranial volume, respectively. RESULTS: The mean (SD) annual rate of change of hippocampal volume [(HR at baseline - HR at follow-up)/HR at baseline/follow-up years×100%] was 0.499 (1.128) (%). In the multivariable-adjusted general linear model, green tea consumption was negatively associated only with the annual rate of change of hippocampal volume (%) [ß (95% CI) for each 1 mL/day increase in green tea consumption = -20.2E-5 (-35.0E-5 to -5.3E-5); P-value = 0.008]. No associations were observed for the annual rate of change of GM or WM volumes. The results remained significant when the analysis was limited to those with stable green tea consumption and were especially evident among individuals aged 65 years and older and among women. CONCLUSIONS: In this study, higher green tea consumption was associated with less annual hippocampal atrophy, and each additional 100 mL/day of green tea intake was related to a reduction of approximately 5% in annual hippocampal atrophy. This association was especially evident among older individuals and among women. Further study in different settings is needed to confirm this association.

Green tea and coffee intake and risk of cognitive decline in older adults: the National Institute for Longevity Sciences, Longitudinal Study of Aging.

OBJECTIVE: To examine the association between green tea and coffee intake and cognitive decline in older adults. DESIGN: A prospective cohort study. The average intake of green tea and coffee in the previous year was assessed through a dietitian interview using a dietary questionnaire. A Mini-Mental State Examination (MMSE) was conducted up to six times biennially. Cognitive decline was screened using the MMSE; its incidence was defined as the first time a score of <27 points was obtained in a biennial test from the baseline. Hazard ratios for incidence of cognitive decline were estimated according to the intake of the two beverages using multivariable Cox proportional hazard regression, controlling for sociodemographic and lifestyle factors. SETTING: The National Institute for Longevity Sciences, Longitudinal Study of Aging (NILS-LSA) in Japan. PARTICIPANTS: Men (n 620) and women (n 685), aged 60-85 years, from the NILS-LSA. RESULTS: During a mean of 5·3 (sd 2·9) years of follow-up, 432 incident cases of cognitive decline were observed. Compared with participants who consumed green tea

＜Editors' Choice＞ Association between green tea intake and risk of cognitive decline, considering glycated hemoglobin level, in older Japanese adults: the NILS-LSA study.

Positive and negative associations with risk of cognitive decline have been reported for glycated hemoglobin (HbA1c) level and green tea (GT) intake, respectively. This study aimed to assess whether the reduction in the risk of cognitive decline with GT intake depended on HbA1c level. The participants were aged ≥60 years at baseline in the cohort study, wherein examinations were conducted biennially from 2000 to 2012. Subjects (n=1,304) who had no cognitive decline during the first survey and who had participated in the follow-up survey at least once were included. The follow-up end point was the first screening time point for cognitive decline (Mini-Mental State Examination score <27) or the last survey participation. With reference to the Japanese Diabetes Society guideline, the cut-off points for HbA1c level were set at 5.6%, 6.0%, and 6.5%, and lower and higher groups were assigned for each cut-off point. In a multiple Cox proportional hazard model, an interaction between GT intake and HbA1c groups for cognitive decline was observed only at HbA1c 6.0% (P-value for interaction [with Bonferroni's correction] <0.05/3). Lower risks of cognitive decline were found for the HbA1c ≥5.6%, ≥6.0%, and <6.5% groups (hazard ratios: 0.59, 0.34, and 0.77; 95% confidence intervals: 0.41-0.88, 0.19-0.61, and 0.56-1.08 for "≥4 times a day" vs. "

Prevalence of Sinusitis Detected by Magnetic Resonance Imaging in Subjects with Dementia or Alzheimer's Disease.

BACKGROUND: It has been reported that periodontitis is associated with Alzheimer's disease. However, the association between paranasal sinusitis and Alzheimer's disease has not been studied, although olfactory dysfunction frequently precedes the progress of dementia or Alzheimer's disease. METHODS: We studied 783 patients (283 men, 500 women; mean age 77.0 ± 7.9 years) who visited the Center for Comprehensive Care and Research on Memory Disorders, National Center for Geriatrics and Gerontology, and 2139 control subjects who participated in a population-based study conducted by the National Institute for Longevity Sciences - Longitudinal Study of Aging (NILS-LSA) in Japan. Sinusitis was evaluated using magnetic resonance imaging (MRI) according to the Lund-Mackay scoring system. A sinusitis score of ≥ 4 was classified as positive and a score of ≤ 3 was classified as negative. RESULTS: The prevalence of positive sinusitis was 6.3% in patients with a mini-mental state examination (MMSE) score of < 24 (n = 507), and 5.7% in patients with Alzheimer's disease (n = 280). The rate of positive sinusitis was7.2% in the control group. The prevalence of sinusitis was not significantly different between normal controls and patients with dementia or Alzheimer's disease after adjustments for age and sex. The rate of positive sinusitis was higher in male than in female subjects in both groups. CONCLUSION: The prevalence of sinusitis in patients with Alzheimer's disease or dementia was not higher than in the general population.

Association between polymorphisms in genes encoding methylenetetrahydrofolate reductase and the risk of Ménière's disease.

Folate metabolism is essential for cellular functioning. Despite extensive research on the roles of folate-metabolism-related gene polymorphisms in the pathophysiology of many diseases, such as cardiovascular disease, cancers, and sudden sensorineural hearing loss, little is known about their association with Ménière's disease (MD). The aim of this study was to investigate the effect of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (C677T and A1298C) on the risk of MD in a Japanese population. We examined the C677T and A1298C (rs1801133 and rs1801131) polymorphisms in the MTHFR gene and compared them between 1946 adults (986 men and 960 women) participating in the National Institute for Longevity Sciences Longitudinal Study of Aging and 86 cases of MD. A multiple logistic regression was performed to obtain odds ratios (ORs) for the risk of MD regarding the MTHFR polymorphisms before (model 1) and after (model 2) adjustment for age and sex factors. The OR of MTHFR C677T for the risk of MD was 0.669 (95% confidence interval [CI], 0.479-0.934) in model 1 and 0.680 (95% CI, 0.484-0.954) in model 2. In contrast, the OR of MTHFR A1298C for the risk of MD was 1.503 (95% CI, 1.064-2.123) in model 1 and 1.505 (95% CI, 1.045-2.167) in model 2. Our results imply that the MTHFR C677T and A1298C polymorphisms are associated with the risk of MD.

Vitamin D deficiency in elderly women in nursing homes: investigation with consideration of decreased activation function from the kidneys.

OBJECTIVES: To determine the approximate percentage of women in nursing homes who have vitamin D deficiency and to investigate whether, in assessing vitamin D status in elderly women, there are problems with measuring only 25 hydroxy-vitamin D(3) (25(OH)D(3) ) and whether decreased vitamin D activation as a result of poor renal function needs to be considered. DESIGN: Cross-sectional study. SETTING: Forty-eight nursing homes in Japan. PARTICIPANTS: Four hundred three women with a mean age of 86.5 living in nursing homes who had participated in a clinical trial for hip protectors and were not bedridden. MEASUREMENTS: At the start of the trial, in addition to general biochemical data, 25(OH)D(3) , 1,25-dihydroxy-vitamin D(3) (1,25(OH)(2) D(3) ), intact parathyroid hormone (intact PTH), calcium (Ca), phosphorus (P), bone alkaline phosphate (BAP), cross-linked N-telopeptide of type I collagen (NTx), and osteocalcin were measured in participants' blood, and statistical analysis was performed. RESULTS: 25(OH)D(3) , which is thought to reflect vitamin D status in the body, was surveyed and found to have a mean value of 16.7 ng/mL. 25(OH)D(3) was less than 16 ng/mL in 49.1% of all participants. Creatinine clearance (CCr) was less than 30 mL/min in 20.1% of participants. Participants with serum 25(OH)D(3) less than 16 ng/mL and CCr less than 30 mL/min had significantly higher levels of intact PTH and serum NTx. Participants with a CCr less than 30 mL/min had significantly lower levels of 1,25(OH)(2) D(3) . CONCLUSION: Frail elderly adults living in nursing homes with poor renal function had lower 1,25(OH)(2) D(3) and higher intact PTH levels and were thus thought to have poorer vitamin D activating capacity. Supplementation with cholecalciferol may be insufficient in people who have poor renal function.

Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials.

BACKGROUND: The MTHFR 677C→T polymorphism has been associated with raised homocysteine concentration and increased risk of stroke. A previous overview showed that the effects were greatest in regions with low dietary folate consumption, but differentiation between the effect of folate and small-study bias was difficult. A meta-analysis of randomised trials of homocysteine-lowering interventions showed no reduction in coronary heart disease events or stroke, but the trials were generally set in populations with high folate consumption. We aimed to reduce the effect of small-study bias and investigate whether folate status modifies the association between MTHFR 677C→T and stroke in a genetic analysis and meta-analysis of randomised controlled trials. METHODS: We established a collaboration of genetic studies consisting of 237 datasets including 59,995 individuals with data for homocysteine and 20,885 stroke events. We compared the genetic findings with a meta-analysis of 13 randomised trials of homocysteine-lowering treatments and stroke risk (45,549 individuals, 2314 stroke events, 269 transient ischaemic attacks). FINDINGS: The effect of the MTHFR 677C→T variant on homocysteine concentration was larger in low folate regions (Asia; difference between individuals with TT versus CC genotype, 3·12 µmol/L, 95% CI 2·23 to 4·01) than in areas with folate fortification (America, Australia, and New Zealand, high; 0·13 µmol/L, -0·85 to 1·11). The odds ratio (OR) for stroke was also higher in Asia (1·68, 95% CI 1·44 to 1·97) than in America, Australia, and New Zealand, high (1·03, 0·84 to 1·25). Most randomised trials took place in regions with high or increasing population folate concentrations. The summary relative risk (RR) of stroke in trials of homocysteine-lowering interventions (0·94, 95% CI 0·85 to 1·04) was similar to that predicted for the same extent of homocysteine reduction in large genetic studies in populations with similar folate status (predicted RR 1·00, 95% CI 0·90 to 1·11). Although the predicted effect of homocysteine reduction from large genetic studies in low folate regions (Asia) was larger (RR 0·78, 95% CI 0·68 to 0·90), no trial has evaluated the effect of lowering of homocysteine on stroke risk exclusively in a low folate region. INTERPRETATION: In regions with increasing levels or established policies of population folate supplementation, evidence from genetic studies and randomised trials is concordant in suggesting an absence of benefit from lowering of homocysteine for prevention of stroke. Further large-scale genetic studies of the association between MTHFR 677C→T and stroke in low folate settings are needed to distinguish effect modification by folate from small-study bias. If future randomised trials of homocysteine-lowering interventions for stroke prevention are undertaken, they should take place in regions with low folate consumption. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).

The effects of aging on distortion-product otoacoustic emissions in adults with normal hearing.

OBJECTIVES: The focus of this study was to determine whether deterioration in cochlear function, as evaluated by distortion-product otoacoustic emission (DPOAE), exists before the elevation of audiometric thresholds occurs during the course of aging. In previous research, variability in normal audiometric thresholds likely contributed to the aging effect on OAE data. Therefore, in selecting subjects, we applied the stringent criterion in pure-tone thresholds (PTT) to limit dispersion among normal-hearing thresholds. DESIGN: We evaluated 331 subjects (136 men and 195 women) of a population-based sample of 2259 adults aged 40 to 82 yr who took part in the Longitudinal Study of Aging. We chose subjects according to the audiometric criterion that thresholds at any of five frequencies, namely 500, 1000, 2000, 4000, and 8000 Hz, did not exceed 15 dB HL. The mean age of our subjects was 48.3 +/- 7.4 yr (range, 41 to 72 yr) in men and 49.6 +/- 7.6 yr (range, 41 to 80 yr) in women. In a univariate analysis, analysis of variance was performed on DPOAE amplitudes and noise estimates at 22 test frequencies, as well as on the PTT. Age groups (40s, 50s, 60s, and above) were considered separately for men and women, without adjustment for any confounding variables. In a multivariate approach, general linear model analyses were performed to focus attention on the impact of age as a continuous variable, and on the influence of PTT on DPOAE levels. The multivariate analysis was conducted separately for men and women. DPOAE amplitudes at nine test frequencies were set as objective variables. Age (continuous variable), PTT at the corresponding test frequency, and interaction between age and PTT at the corresponding test frequency were evaluated as explanatory variables with adjustment for static admittance, history of ear disease (yes = 1), and history of occupational noise exposure (yes = 1). RESULTS: Of the 22 test frequencies, we found a statistically significant difference in DPOAE amplitudes among age groups at four test frequencies in men, ranging from 4761 to 6165 Hz, and at all but the 3088 Hz test frequency in women. Despite the stringent audiometric inclusion criterion, statistically significant differences in the mean PTT among the age groups were observed at 4000 Hz in men and at all five tested frequencies in women. Multivariate analyses demonstrated a significant negative effect of age on DPOAE levels at 1086 Hz f2 frequency in men and at the 1184, 2002, 2185, 4004, and 4358 Hz f2 frequencies in women. Regarding PTT, neither main nor interactive effect on DPOAE amplitude was statistically significant at any of nine test frequencies. The goodness-of-fit of the model, in terms of R2, ranged from 0.05 to 0.11 in men and from 0.11 to 0.18 in women. CONCLUSIONS: The present analyses substantiated the hypothesis DPOAEs deteriorate with age independently of hearing sensitivity. The aging effect on DPOAE measures was observed more in women than in men. We conclude that DPOAE measurements in audiometrical normal-hearing elderly may provide early indications of cochlear damage because of aging.

Dietary supplement use by community-living population in Japan: data from the National Institute for Longevity Sciences Longitudinal Study of Aging (NILS-LSA).

BACKGROUND: There are few studies about dietary supplement use and nutrient intake from these products in Japan. The purpose of this study was to clarify (1) the prevalence of dietary supplement use, (2) the characteristics of dietary supplement users, (3) nutrient intake from dietary supplements, and (4) the existence of dietary supplement users who took excessive nutrients from these products. METHODS: To collect the information on dietary supplement use in the previous year and nutrient intake from these products, we conducted a self-administered dietary supplement frequency questionnaire. The subjects were 2,259 people aged 40-82 years. Dietary supplements were grouped into 8 major categories. A dietary supplement database was developed to estimate nutrient intake from these products. Excess users were defined as people who consumed more nutrient than the tolerable upper intake level of the Dietary Reference Intakes for Japanese. RESULTS: In the previous year, 55 % of males and 61 % of females consumed dietary supplements. Dietary supplement use was especially prevalent in females, subjects who felt unhealthy, and subjects who were more careful of maintaining an appropriate weight, though the association was affected by the frequency of dietary supplement use. The most common dietary supplements were drink type in males and vitamins in females. Some nutrient values obtained from dietary supplements were higher than those from food. Excess users were found for intake of vitamin A, B(6), K, niacin, iron, and magnesium. CONCLUSIONS: It is important to clarify dietary supplement use and to estimate nutrient intake from these products.