Iron Status and Risk of Heart Disease, Stroke, and Diabetes: A Mendelian Randomization Study in European Adults.

BACKGROUND: The relevance of iron status biomarkers for coronary artery disease (CAD), heart failure (HF), ischemic stroke (IS), and type 2 diabetes (T2D) is uncertain. We compared the observational and Mendelian randomization (MR) analyses of iron status biomarkers and hemoglobin with these diseases. METHODS AND RESULTS: Observational analyses of hemoglobin were compared with genetically predicted hemoglobin with cardiovascular diseases and diabetes in the UK Biobank. Iron biomarkers included transferrin saturation, serum iron, ferritin, and total iron binding capacity. MR analyses assessed associations with CAD (CARDIOGRAMplusC4D [Coronary Artery Disease Genome Wide Replication and Meta-Analysis Plus The Coronary Artery Disease Genetics], n=181 522 cases), HF (HERMES [Heart Failure Molecular Epidemiology for Therapeutic Targets), n=115 150 cases), IS (GIGASTROKE, n=62 100 cases), and T2D (DIAMANTE [Diabetes Meta-Analysis of Trans-Ethnic Association Studies], n=80 154 cases) genome-wide consortia. Observational analyses demonstrated J-shaped associations of hemoglobin with CAD, HF, IS, and T2D. In contrast, MR analyses demonstrated linear positive associations of higher genetically predicted hemoglobin levels with 8% higher risk per 1 SD higher hemoglobin for CAD, 10% to 13% for diabetes, but not with IS or HF in UK Biobank. Bidirectional MR analyses confirmed the causal relevance of iron biomarkers for hemoglobin. Further MR analyses in global consortia demonstrated modest protective effects of iron biomarkers for CAD (7%-14% lower risk for 1 SD higher levels of iron biomarkers), adverse effects for T2D, but no associations with IS or HF. CONCLUSIONS: Higher levels of iron biomarkers were protective for CAD, had adverse effects on T2D, but had no effects on IS or HF. Randomized trials are now required to assess effects of iron supplements on risk of CAD in high-risk older people.

The potential causal path between periodontitis stage diagnosis and vegetable consumption is mediated by loss of posterior functional tooth units and masticatory function.

AIM: Emerging evidence points to a two-way relationship between periodontitis and dietary choices and, thus, nutrition. This study aimed to assess the potential cause-effect relationship between the periodontitis stage, loss of functional tooth units (FTUs), masticatory function, and intake of different food groups using path analysis. MATERIALS AND METHODS: A single calibrated examiner determined the periodontitis stage of a consecutive sample of 241 Chinese subjects reporting for tooth replacement. Their masticatory function was quantified by the mixing ability of a two-colour chewing gum. Validated food frequency questionnaires were used to calculate the intake of 33 food group items by an experienced calibrated rater. After verification of assumptions, visual structural equation modeling was performed with Amos 23. The consistency of results and the potential modifying effect of age were assessed in 9043 subjects from the NHANES database. RESULTS: Highly significant models were constructed using periodontitis stage and age as exogenous factors. Periodontitis stage diagnosis significantly affected the number of posterior FTUs and oral health-related quality of life (OHRQoL, path coefficient [PC] = -0.55 and -0.20, p < .05, respectively). In the model, FTUs also had an independent effect on OHRQoL (PC = 0.23, p < .05). FTUs determined the level of masticatory function (PC = -0.38, p < .05), which in turn affected vegetable intake but not fruit or meat intake (PC = -0.18, p < .0.5, PC = 0.06, NS and PC = 0.11, NS, respectively). The effect of age was significant for vegetable and meat intake and was also correlated with periodontitis stage diagnosis. Analysis of the NHANES database confirmed the negative impact of periodontitis on the number of occluding pairs and vegetable consumption for the 18-44, 45-60 and >60 age groups. CONCLUSIONS: Periodontitis showed a potential cause-effect pathway affecting vegetable intake across cultures and age groups. The size of the effect is potentially of clinical and public health significance. Additional studies, including intervention trials, are required to test this potential mechanism linking oral health to nutrition.

Cardiovascular risk burden, dementia risk and brain structural imaging markers: a study from UK Biobank.

Background: Cardiovascular risk burden is associated with dementia risk and neurodegeneration-related brain structure, while the role of genetics and incident cardiovascular disease (CVD) remains unclear. Aims: To examine the association of overall cardiovascular risk burden with the risk of major dementia subtypes and volumes of related brain regions in a large sample, and to explore the role of genetics and CVD onset. Methods: A prospective study among 354 654 participants free of CVD and dementia (2006-2010, mean age 56.4 years) was conducted within the UK Biobank, with brain magnetic resonance imaging (MRI) measurement available for 15 104 participants since 2014. CVD risk burden was evaluated by the Framingham General Cardiovascular Risk Score (FGCRS). Dementia diagnosis was ascertained from inpatient and death register data. Results: Over a median 12.0-year follow-up, 3998 all-cause dementia cases were identified. Higher FGCRS was associated with increased all-cause dementia risk after adjusting for demographic, major lifestyle, clinical factors and the polygenic risk score (PRS) of Alzheimer's disease. Comparing the high versus low tertile of FGCRS, the odds ratios (ORs) and 95% confidence intervals (CIs) were 1.26 (1.12 to 1.41) for all-cause dementia, 1.67 (1.33 to 2.09) for Alzheimer's disease and 1.53 (1.07 to 2.16) for vascular dementia (all ptrend<0.05). Incident stroke and coronary heart disease accounted for 14% (95% CI: 9% to 21%) of the association between FGCRS and all-cause dementia. Interactions were not detected for FGCRS and PRS on the risk of any dementia subtype. We observed an 83% (95% CI: 47% to 128%) higher all-cause dementia risk comparing the high-high versus low-low FGCRS-PRS category. For brain volumes, higher FGCRS was associated with greater log-transformed white matter hyperintensities, smaller cortical volume and smaller grey matter volume. Conclusions: Our findings suggest that the positive association of cardiovascular risk burden with dementia risk also applies to major dementia subtypes. The association of cardiovascular risk burden with all-cause dementia is largely independent of CVD onset and genetic predisposition to dementia.

Denture use and risk for cardiometabolic disease: observational and Mendelian randomization analyses.

AIMS: Denture use may potentially increase the risk of cardiometabolic diseases (CMDs), but the casual relevance and strength of the associations are currently unknown. METHODS AND RESULTS: A total of 495 938 participants from the UK Biobank were included in the observational analyses. Linkage disequilibrium score (LDSC) regression and Mendelian randomization analyses were employed to estimate genetic correlation and the associations between the genetic liability for denture use with coronary artery disease, myocardial infarction, heart failure (HF), any stroke (AS), ischaemic stroke, haemorrhagic stroke, type 2 diabetes (T2D), and related clinical risk factors. In observational analysis, denture use was associated with 14-25% higher risks of various CMDs. The LDSC analysis found that denture use showed a positive genetic correlation with CMDs (rg 0.21-0.38). Genetic liability for denture use was associated with an elevated risk of HF [odds ratio: 1.49 (1.20-1.83)] and T2D [1.11 (1.01-1.24)]. By integrating genetic summary data of denture use with the sum of decayed, missing, and filled tooth surfaces (DMFS), a clinical measure of dental caries obtained from an independent source, genetically determined denture use/DMFS was also associated with an elevated risk of AS [1.21 (1.04-1.40)]. Furthermore, genetically predicted denture use/DMFS was significantly associated with established cardiometabolic risk factors, including HDL cholesterol, triglycerides, waist circumference, waist-to-hip ratio, and height. CONCLUSION: Our study supported potential causal associations between the genetic liability for denture use and risks for HF, AS, T2D, and related clinical risk factors. These findings may inform prevention and intervention strategies targeting dental diseases and CMDs.

This study examined the association of denture use with cardiometabolic diseases (CMDs) and related clinical risk factors through Mendelian randomization analyses using data from UK Biobank and published consortia. Genetic liability for denture use was associated with an 11­49% higher risk of heart failure, stroke, and type 2 diabetes.The potential causal relationship between denture use and CMDs was further strengthened by the associations of denture use with HDL cholesterol, triglycerides, waist circumference, waist-to-hip ratio, and height, which are among the major risk factors of CMDs.

Associations of the Mediterranean-DASH Intervention for Neurodegenerative Delay diet with brain structural markers and their changes.

INTRODUCTION: The associations of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet with brain structural changes are unclear. METHODS: Among 26,466 UK Biobank participants, a 15-point MIND score was calculated from 24-hour diet recalls from 2009 to 2012. We assessed its associations with 17 magnetic-resonance-derived brain volumetric markers and their longitudinal changes and explored whether genetic factors modify the associations. RESULTS: Higher MIND adherence was associated with larger volumes of thalamus, putamen, pallidum, hippocampus, and accumbens (beta per 3-unit increment ranging from 0.024 to 0.033) and lower white matter hyperintensities (P-trends < 0.05), regardless of genetic predispositions of Alzheimer's disease. MIND score was not associated with their longitudinal changes (P > 0.05) over a median of 2.2 years among participants with repeated imaging assessments (N = 2963), but was associated with slower atrophy in putamen (beta: 0.026, P-trend = 0.044) and pallidum (beta: 0.030, P-trend = 0.033) among APOE Îµ4 non-carriers (N = 654). DISCUSSION: The MIND diet showed beneficial associations with certain brain imaging markers, and its associations with long-term brain structural changes warrants future investigation. HIGHLIGHTS: Adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet was significantly associated with higher volumes and larger gray matter volumes in certain brain regions in UK adults, and the associations were not modified by genetic factors. No significant associations were observed between MIND diet and longitudinal changes in the investigated brain structural markers over a median of 2.2 years. Higher MIND score was significantly associated with slower atrophy in the putamen and pallidum among APOE Îµ4 non-carriers.

Family History of AD/Dementia, Polygenic Risk Score for AD, and Parkinson's Disease.

Background: Co-occurrence of Alzheimer's disease (AD) and Parkinson's disease (PD) has been observed. However, there is limited knowledge on how family history of AD is associated with PD. Objectives: To prospectively examine the associations of family history of AD/dementia and polygenic risk score for AD (AD-PRS) with PD risk. Methods: The study included 477,190 participants from UK Biobank who were free of PD at baseline (2006-2010) and had complete data on the studied exposure variables, family history of AD and AD-PRS. Cox proportional hazards model was used to examine the hazard ratios (HRs) and their 95% confidence intervals (CIs) of family history of AD/dementia and AD-PRS for PD risk. We also conducted mediation analysis to examine the proportion of the association between family history of AD/dementia and PD risk that could be mediated by AD-PRS. Results: During a median follow-up of 12.5 years, we identified 2550 incidences of PD. Family history of AD/dementia (adjusted HR = 1.21; 95% CI 1.09-1.35) and AD-PRS (adjusted HR = 1.10 per 1 unit increment; 95% CI 1.05-1.14) were associated with PD risk, after adjustment for age, sex, lifestyle factors, and other potential confounders. The association between family history of AD/dementia and PD risk was mediated by 13.1% by the AD-PRS. As expected, we observed significant associations of family history of AD/dementia and AD-PRS with risks of dementia and AD (P < 0.001 for all). Conclusions: Family history of AD/dementia appeared to be associated with PD risk, and this association could be mediated partially by AD-related genetic factors.

Prevalent stroke, age of its onset, and post-stroke lifestyle in relation to dementia: A prospective cohort study.

INTRODUCTION: The association of age at stroke onset with dementia and the role of post-stroke lifestyle on dementia risk remains unclear. METHODS: We leveraged data of 496,251 dementia-free participants from UK Biobank and explored the relationship between age at stroke onset and incident dementia. Among 8328 participants with stroke history, we further investigated the association of a healthy lifestyle with risk of dementia. RESULTS: Participants with stroke history had a higher risk of dementia (hazard ratio [HR], 2.02). The association was stronger among participants with stroke onset at a younger age (≤50: HR, 2.63) compared with those at the age > 50 years (50-60: HR, 2.17; ≥60: HR, 1.58). Among participants with stroke history, a favorable lifestyle was associated with a lower risk of incident dementia. DISCUSSION: Stroke onset in earlier life stage predicted a higher risk for dementia, but a favorable post-stroke lifestyle may protect against dementia.

Association of Type 2 Diabetes Mellitus with Cognitive Function in Adults: A Prospective Cohort Study.

BACKGROUND: The Cognitive role of untreated type 2 diabetes mellitus (T2DM) has been less well substantiated. OBJECTIVE: We sought to explore the prospective association of T2DM and untreated T2DM with cognitive function among middle-aged and older Chinese adults. METHODS: Data of 7,230 participants without baseline brain damage/mental retardation, or memory-related diseases in China Health and Retirement Longitudinal Study (CHARLS) from 2011- 2012 to 2015, were analyzed. Fasting plasma glucose and self-reported information on T2DM diagnosis and treatment were assessed. Participants were categorized into normoglycemia, impaired fasting glucose (IFG), and T2DM (including untreated and treated T2DM) groups. Episodic memory and executive function were assessed by modified Telephone Interview for Cognitive Status every two years. We used generalized estimating equation model to examine the association of baseline T2DM status with cognitive function in succeedingyears. RESULTS: Compared to those with normoglycemia, T2DM was associated with worse overall cognitive function after controlling for demographic variables, lifestyles, follow-up time, major clinical factors, and baseline cognitive function, although the associations were statistically non-significant (ß= -0.19, 95% CI: -0.39, 0.00). However, a significant association was mainly observed for those with untreated T2DM (ß= -0.26, 95% CI: -0.47, -0.04), especially in the domain of executive function (ß= -0.19, 95% CI: -0.35, -0.03). In general, IFG and treated T2DM individuals had similar levels of cognitive function with normoglycemia participants. CONCLUSION: Our findings supported a detrimental role of untreated T2DM on cognitive function among middle-aged and older adults. Screening and early treatment for T2DM are warranted for maintaining better cognitive function in later life.

Adherence to a healthy lifestyle and brain structural imaging markers.

Previous research has linked specific modifiable lifestyle factors to age-related cognitive decline in adults. Little is known about the potential role of an overall healthy lifestyle in brain structure. We examined the association of adherence to a healthy lifestyle with a panel of brain structural markers among 2,413 participants in PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study in China and 19,822 participants in UK Biobank (UKB). A healthy lifestyle score (0-5) was constructed based on five modifiable lifestyle factors: diet, physical activity, smoking, alcohol consumption, and body mass index. Validated multimodal neuroimaging markers were derived from brain magnetic resonance imaging. In the cross-sectional analysis of PRECISE, participants who adopted four or five low-risk lifestyle factors had larger total brain volume (TBV; ß = 0.12, 95% CI: - 0.02, 0.26; p-trend = 0.05) and gray matter volume (GMV; ß = 0.16, 95% CI: 0.01, 0.30; p-trend = 0.05), smaller white matter hyperintensity volume (WMHV; ß = - 0.35, 95% CI: - 0.50, - 0.20; p-trend < 0.001) and lower odds of lacune (Odds Ratio [OR] = 0.48, 95% CI: 0.22, 1.08; p-trend = 0.03), compared to those with zero or one low-risk factors. Meanwhile, in the prospective analysis in UKB (with a median of 7.7 years' follow-up), similar associations were observed between the number of low-risk lifestyle factors (4-5 vs. 0-1) and TBV (ß = 0.22, 95% CI: 0.16, 0.28; p-trend < 0.001), GMV (ß = 0.26, 95% CI: 0.21, 0.32; p-trend < 0.001), white matter volume (WMV; ß = 0.08, 95% CI: 0.01, 0.15; p-trend = 0.001), hippocampus volume (ß = 0.15, 95% CI: 0.08, 0.22; p-trend < 0.001), and WMHV burden (ß = - 0.23, 95% CI: - 0.29, - 0.17; p-trend < 0.001). Those with four or five low-risk lifestyle factors showed approximately 2.0-5.8 years of delay in aging of brain structure. Adherence to a healthier lifestyle was associated with a lower degree of neurodegeneration-related brain structural markers in middle-aged and older adults.

Sugary beverages and genetic risk in relation to brain structure and incident dementia: a prospective cohort study.

BACKGROUND: The relation of intake of sugary beverages and genetic predisposition to the long-term risk of dementia and brain structure remains unclear. OBJECTIVES: This study aimed to assess the associations of sugar-sweetened beverages (SSBs), artificially-sweetened beverages (ASBs), and natural juices (NJs) and the genetic predisposition with dementia risk and brain structure. METHODS: We included 177,926 UK Biobank participants without dementia at baseline and followed them until March 2021. Intake of SSBs, ASBs, and NJs was assessed using repeated web-based 24-h dietary recalls from 2009 to 2012. We calculated a polygenic risk score (PRS) to indicate genetic predisposition of dementia for each individual. We estimated the HRs and 95% CIs using Cox proportional hazard models for dementia risk and ß coefficients and 95% CIs using linear models for brain imaging markers. RESULTS: During study follow-up (mean = 9.5 years), 1293 participants developed dementia (69.1 cases/100,000 person-years) excluding dementia cases within the first 2 years. Higher intake of SSBs and ASBs (>2 units/d compared with none) was each associated with a higher risk of dementia (HR: 1.34; 95% CI: 1.01, 1.77; P-trend = 0.040 for SSBs and 1.20; 95% CI: 0.84, 1.72; P-trend = 0.004 for ASBs). In contrast, moderate intake of NJs (>0-1 unit/d compared with none) was related to a lower dementia risk (HR: 0.77; 95% CI: 0.68, 0.87), a larger volume of brain gray matter (ß = 0.05; 95% CI: 0.02, 0.08), and a lower volume of white matter hyperintensities (ß = -0.07; 95% CI: -0.11, -0.03). The associations were not significantly modified by genetic risk (P-interactions = 0.839 for SSB × PRS, 0.732 for ASB × PRS, and 0.950 for NJ × PRS). CONCLUSIONS: Higher SSB and ASB intake was associated with higher risk of dementia, and moderate NJ intake was associated with a lower risk of dementia. Am J Clin Nutr 20XX;xx:xx-xx.

Long-term variability in physiological measures in relation to mortality and epigenetic aging: prospective studies in the USA and China.

BACKGROUND: Visit-to-visit body weight variability (BWV), pulse rate variability (PRV), and blood pressure variability (BPV) have been respectively linked to multiple health outcomes. The associations of the combination of long-term variability in physiological measures with mortality and epigenetic age acceleration (EAA) remain largely unknown. METHODS: We constructed a composite score of physiological variability (0-3) of large variability in BWV, PRV, and BPV (the top tertiles) in 2006/2008-2014/2016 in the Health and Retirement Study (HRS) and 2011-2015 in the China Health and Retirement Longitudinal Study (CHARLS). All-cause mortality was documented through 2018. EAA was calculated using thirteen DNA methylation-based epigenetic clocks among 1047 participants in a substudy of the HRS. We assessed the relation of the composite score to the risk of mortality among 6566 participants in the HRS and 6906 participants in the CHARLS by Cox proportional models and then investigated its association with EAA using linear regression models. RESULTS: A higher score of variability was associated with higher mortality risk in both cohorts (pooled hazard ratio [HR] per one-point increment, 1.27; 95% confidence interval [CI], 1.18, 1.39; P-heterogeneity = 0.344), after adjustment for multiple confounders and baseline physiological measures. Specifically, each SD increment in BWV, PRV, and BPV was related to 21% (95% CI: 15%, 28%), 6% (0%, 13%), and 12% (4%, 19%) higher hazard of mortality, respectively. The composite score was significantly related to EAA in second-generation clocks trained on health outcomes (e.g., standardized coefficient = 0.126 in the Levine clock, 95% CI: 0.055, 0.196) but not in most first-generation clocks trained on chronological age. CONCLUSIONS: Larger variability in physiological measures was associated with a higher risk of mortality and faster EAA.

Age- and sex-specific modifiable risk factor profiles of dementia: evidence from the UK Biobank.

Dementia constitutes a worldwide concern. To characterize the age- and sex-specific modifiable risk factor profiles of dementia, we included 497,401 UK Biobank participants (mean age = 56.5 years) without dementia at baseline (2006-2010) and followed them until March 2021. Cox proportional hazard models were used to estimate the age- and sex-specific hazard ratios (HRs) of incident dementia associated with socioeconomic (less education and high Townsend deprivation index), lifestyle (non-moderate alcohol intake, current smoking, suboptimal diet, physical inactivity, and unhealthy sleep duration), and health condition factors (hypertension, diabetes, cardiovascular diseases, and depressive symptoms). We also calculated the population attributable fractions (PAFs) of these factors. During follow-up (mean = 11.6 years), we identified 6564 dementia cases. HRs for the risk factors were similar between the sexes, while most factors showed stronger associations among younger participants. For example, the HRs of smoking were 1.74 (95% CI: 1.23, 2.47) for individuals aged < 50 years, and 1.18 (1.05, 1.33) for those aged ≥ 65 years. Overall, 46.8% (37.4%, 55.2%) of dementia cases were attributable to the investigated risk factors. The PAFs of the investigated risk factors also decreased with age, but that for health condition risk factors decreased with lower magnitude than socioeconomic and lifestyle risk factors. The stronger associations and greater PAFs of several modifiable risk factors for dementia among younger adults than older participants underscored the importance of dementia prevention from an earlier stage across the adult life course.

Sleep Duration and Risks of Incident Cardiovascular Disease and Mortality Among People With Type 2 Diabetes.

OBJECTIVE: People with type 2 diabetes may have insufficient or prolonged sleep that could accelerate cardiovascular disease (CVD) onset, but existing evidence from prospective studies has been limited. We examined the association of sleep duration with CVD incidence and mortality in this high-risk population. RESEARCH DESIGN AND METHODS: This prospective study included 18,876 participants with type 2 diabetes in the UK Biobank who were free of CVD and cancer at baseline. Habitual sleep duration was obtained using a baseline questionnaire. Cox proportional hazards regression models were used to examine the association between sleep duration and CVD events. RESULTS: During an average follow-up of 11.0-12.0 years, we documented 2,570 incident cases of atherosclerotic cardiovascular disease (ASCVD) and 598 CVD deaths. Compared with sleeping for 7 h/day, the multivariable-adjusted hazard ratios of ≤5 and ≥10 h/day were 1.26 (95% CI 1.08, 1.48) and 1.41 (1.16, 1.70) for incident ASCVD, 1.22 (0.99, 1.50) and 1.16 (0.88, 1.52) for coronary artery disease, 1.70 (1.23, 2.35) and 2.08 (1.44, 3.01) for ischemic stroke, 1.02 (0.72, 1.44) and 1.45 (1.01, 2.10) for peripheral artery disease, and 1.42 (1.02, 1.97) and 1.85 (1.30, 2.64) for CVD mortality. Similar results were observed in most sensitivity analyses that aimed to address potential reverse causation and in the joint analyses of sleep duration and metabolic control or diabetes severity status. CONCLUSIONS: Short and long sleep durations were independently associated with increased risks of CVD onset and death among people with type 2 diabetes.

Association of the number of natural teeth with dietary diversity and nutritional status in older adults: A cross-sectional study in China.

AIM: To investigate the association of the number of natural teeth with overall dietary diversity and nutritional status in a nationally representative study among older adults in China. MATERIALS AND METHODS: A cross-sectional analysis was conducted among community-dwelling adults aged 65 years or older from the Chinese Longitudinal Healthy Longevity Study. According to the self-reported number of natural teeth, participants were categorized into ≥20, 10-19, 1-9 natural teeth, and edentulous. Dietary diversity score (DDS) was constructed based on intake frequencies of 10 food groups assessed by a simplified food frequency questionnaire. The geriatric nutritional risk index was used to measure the malnutrition status (i.e., normal, mild malnutrition, and moderate-to-severe malnutrition) among a subgroup of participants. Linear and multinomial logistic regression models were used to examine the corresponding associations. RESULTS: Among 54,796 study participants, the mean (SD) age was 87.86 (11.45) years, 82.7% had poor dentition (<20 natural teeth), and 27.3% wore dentures. After multivariable adjustment, participants with poor dentition had lower DDSs (ßedentulous  = -0.39, 95% confidence interval [CI], -0.48, -0.30; ß1-9 teeth  = -0.46, 95% CI, -0.55, -0.37; ß10-19 teeth  = -0.36, 95% CI, -0.46, -0.26) than those with 20 natural teeth or more. For individual food items, edentulous, 1-9 and 10-19 natural teeth were associated with lower odds of regular intake of fresh fruits, fresh vegetables, meat, fish and aquatic products, eggs, legumes, preserved vegetables, tea, and garlic, but higher odds of regular intake of sugar and sweets. Among participants with poor dentition, individuals without dentures had lower intake frequencies of most food groups than those wearing dentures. In addition, poor dentition was related to lower odds of normal nutritional status (odds ratio = 0.49, 95% CI, 0.27, 0.89). CONCLUSIONS: Older adults with poor dentition had significantly lower dietary diversity and worse nutritional status. Future studies are warranted to identify effective interventions to improve the dietary quality and nutrition status among partially and fully edentulous individuals, including those with Stage IV periodontitis.

Global Burden Attributable to High Low-Density Lipoprotein-Cholesterol From 1990 to 2019.

Background: High low-density lipoprotein-cholesterol (LDL-C) is a public health issue contributing to ischemic heart disease (IHD) and stroke. Method: In this ecological study, we collected summary exposure values (SEVs), deaths, disability-adjusted life of years (DALYs), and Social Demographic Index (SDI) of high LDL-C from 1990 to 2019 using the query tool from the Global Burden of Disease (GBD) Collaborative Network. Outcomes include SEVs, deaths, and DALYs attributable to high LDL-C stratified by sex, age, region, SDI, countries, and territories. Estimated annual percentage changes (EAPCs) were applied to estimate annual trends of changes in these outcomes. We applied the weighted segmented regression with break-point estimation to detect the linear piecewise relationship between SDI and high LDL-C disease burden. Results: Globally, 3.00 million (95% uncertainty interval [UI], 2.35-3.76 million) people in 1990 and 4.40 million (95% UI, 3.30-5.65 million) people died from high LDL-C in 2019. The absolute annual burden from deaths and DALYs attributed to high LDL-C increased by 46% (95% UI, 35-56%) and 41% (95% UI, 31-50%) from 1990 to 2019. The age-standardized SEV, death, and DALY was decreased by 9% (95% UI, -11 to -8%), 37% (95% UI, -41-33%), and 32% (95% UI, -37 to -28%), respectively, during the study period. There was a negative association between SDI and high LDL-C-related age-standardized death and DALY rates when SDI surpassed 0.71 and 0.71, respectively. Conclusion: Although the overall age-standardized burden of high LDL-C is controlled in the past 30 years, it remains increasing in moderate SDI countries, and decreasing trends are disappearing in high SDI countries. New challenges require new actions stratified by countries with different SDI levels.

Weight Gain After Smoking Cessation and Cancer Risk in 3 Prospective Cohorts in the United States.

BACKGROUND: It remains unknown how cancer risks vary by duration of smoking cessation and whether the benefit is attenuated by postcessation weight gain. METHODS: We prospectively followed 198 565 persons from the Nurses' Health Study (1978-2016), Nurses' Health Study II (1991-2017), and Health Professionals Follow-up Study (1988-2016) who were free of cancer at baseline. We used proportional hazard Cox models to compare cancer risk between current smokers and former smokers with different durations of smoking cessation and postcessation weight gains. RESULTS: During 4 718 199 person-years of follow-up, we identified 32 456 cases of total cancer. Compared with current smokers, the risks for total and smoking-related cancer in past smokers were reduced to the level similar to never smokers after abstaining smoking for more than 26 years, with the hazard ratio of 0.69 (95% confidence interval [CI] = 0.63 to 0.76) for total cancer and 0.31 (95% CI = 0.26 to 0.37) for smoking-related cancer, whereas no risk reduction was found for obesity-related cancer. Comparing former smokers with current smokers, the multivariable-adjusted hazard ratios for postcessation weight gain of 0-4.9 kg, 5-9.9 kg, and 10 kg or higher were 0.85 (95% CI = 0.81 to 0.89), 0.88 (95% CI = 0.83 to 0.93), and 0.93 (95% CI = 0.88 to 1.00) for total cancer and 0.62 (95% CI = 0.58 to 0.67), 0.65 (95% CI = 0.60 to 0.71), and 0.71 (95% CI = 0.65 to 0.78) for total smoking-related cancer. In contrast, higher weight gain following smoking cessation was associated with a modest increased obesity-related cancer risk. CONCLUSION: Smoking cessation overall has a strong net association with lower risk of total cancer irrespective of weight gain. However, this inverse association may be attenuated by substantial postcessation weight gain, largely because of an increased risk of obesity-related cancers.

Isocaloric-restricted Mediterranean Diet and Chinese Diets High or Low in Plants in Adults With Prediabetes.

CONTEXT: Calorie restriction plus dietary advice is suggested as a preventive strategy for individuals with obesity and prediabetes; however, optimal diet is still debatable. We aimed to compare the effects of Mediterranean diet (MD) and Chinese diets high or low in plants on body weight and glucose homeostasis among high-risk Chinese. SUBJECTS AND METHODS: In this parallel-arm randomized controlled trial, 253 Chinese adults aged 25 to 60 years with a body mass index ≥ 24.0 kg/m2 and fasting blood glucose ≥ 5.6 mmol/L were randomly assigned to 3 isocaloric-restricted diets: MD (n = 84), a traditional Jiangnan diet high in plants (TJD, n = 85), or a control diet low in plants (CD, n = 84). During the 6-month trial, a 5-weekday full-feeding regimen was followed, along with mobile app-based monitoring. Abdominal fat measurement (magnetic resonance imaging), oral glucose tolerance test (OGTT), and continuous glucose monitoring (CGM) were conducted at baseline and 3 and 6 months. RESULTS: With a 25% calorie restriction for 6 months, weight deduction was 5.72 kg (95% confidence interval, 5.03-6.40) for MD, 5.05 kg (4.38-5.73) for TJD, and 5.38 kg (4.70-6.06) for CD (Ptime < 0.0001). No between-group differences were found for fasting glucose, insulin, and the Matsuda index from OGTT. Notably, CD had significantly longer time below range (glucose < 3.9 mmol/L) than MD (0.81% [0.21-1.40], P = 0.024) and marginally longer time than TJD (0.56% [-0.03 to 1.15], P = 0.065), as measured by CGM. CONCLUSIONS: With the 6-month isocaloric-restricted feeding, TJD and MD achieved comparable weight deduction and improved glucose homeostasis, whereas CD showed a higher risk for hypoglycemia.

Lipidomic Signatures of Dairy Consumption and Associated Changes in Blood Pressure and Other Cardiovascular Risk Factors Among Chinese Adults.

BACKGROUND: Omics data may provide a unique opportunity to discover dairy-related biomarkers and their linked cardiovascular health. METHODS: Dairy-related lipidomic signatures were discovered in baseline data from a Chinese cohort study (n=2140) and replicated in another Chinese study (n=212). Dairy intake was estimated by a validated food-frequency questionnaire. Lipidomics was profiled by high-coverage liquid chromatography-tandem mass spectrometry. Associations of dairy-related lipids with 6-year changes in cardiovascular risk factors were examined in the discovery cohort, and their causalities were analyzed by 2-sample Mendelian randomization using available genome-wide summary data. RESULTS: Of 350 lipid metabolites, 4 sphingomyelins, namely sphingomyelin (OH) C32:2, sphingomyelin C32:1, sphingomyelin (2OH) C30:2, and sphingomyelin (OH) C38:2, were identified and replicated to be positively associated with total dairy consumption (ß=0.130 to 0.148; P<1.43×10-4), but not or weakly with nondairy food items. The score of 4 sphingomyelins showed inverse associations with 6-year changes in systolic (-2.68 [95% CI, -4.92 to -0.43]; P=0.019), diastolic blood pressures (-1.86 [95% CI, -3.12 to -0.61]; P=0.004), and fasting glucose (-0.25 [95% CI, -0.41 to -0.08]; P=0.003). Mendelian randomization analyses further revealed that genetically inferred sphingomyelin (OH) C32:2 was inversely associated with systolic (-0.57 [95% CI, -0.85 to -0.28]; P=9.16×10-5) and diastolic blood pressures (-0.39 [95% CI, -0.59 to -0.20]; P=7.09×10-5). CONCLUSIONS: The beneficial effects of dairy products on cardiovascular health might be mediated through specific sphingomyelins among Chinese with overall low dairy consumption.

Associations of erythrocyte polyunsaturated fatty acids with incidence of stroke and stroke types in adult Chinese: a prospective study of over 8000 individuals.

PURPOSE: There is limited and inconsistent evidence about the relationships of erythrocyte polyunsaturated fatty acids (PUFAs) with stroke and stroke types, particularly in China where the stroke rates are high. We aimed to investigate the associations of different erythrocyte PUFAs with incidence of total stroke, ischemic stroke (IS), and intracerebral hemorrhage (ICH) in Chinese adults. METHODS: In the prospective China Kadoorie Biobank, erythrocyte PUFAs were measured using gas chromatography in 10,563 participants who attended 2013-14 resurvey. After a mean follow-up of 3.8 years, 412 incident stroke cases (342 IS, 53 ICH) were recorded among 8,159 participants without prior vascular diseases or diabetes. Cox regression yielded adjusted hazard ratios (HRs) for stroke associated with 13 PUFAs. RESULTS: Overall, the mean body mass index was 24.0 (3.4) kg/m2 and the mean age was 58.1 (9.9) years. In multivariable analyses, 18:2n-6 was positively associated with ICH (HR = 2.33 [95% CIs 1.41, 3.82] for top versus bottom quintile, Ptrend = 0.007), but inversely associated with IS (0.69 [0.53,0.90], Ptrend = 0.027), while 20:3n-6 was positively associated with risk of IS (1.64 [1.32,2.04], Ptrend < 0.001), but not with ICH. Inverted-U shape curve associations were observed of 20:5n-3 with IS (Pnonlinear = 0.002) and total stroke (Pnonlinear = 0.008), with a threshold at 0.70%. After further adjustment for conventional CVD risk factors and dietary factors, these associations remained similar. CONCLUSION: Among relatively lean Chinese adults, erythrocyte PUFAs 18:2n-6, 20:3n-6 and 20:5n-3 showed different associations with risks of IS and ICH. These results would improve the understanding of stroke etiology.

Plasma folate levels in relation to cognitive impairment: a community-based cohort of older adults in China.

PURPOSE: Lower plasma level of folate has been associated with an increased risk of age-related cognitive impairment. However, studies that examined this relation have yielded mixed results. We aimed to examine the prospective association of plasma folate level with risk of cognitive impairment in a community-based prospective cohort of older adults in China. METHODS: This study included 615 participants (mean age: 76.3 years) without baseline cognitive impairment from the Rugao Longevity and Ageing Study (RuLAS). We used logistic regression to examine the prospective association between baseline plasma folate and risk of cognitive impairment in the next two years. Fasting blood samples were collected and assayed for plasma folate level at baseline. Cognitive impairment was defined as Hasegawa Dementia Scale (HDS) score ≤ 21.5 points. RESULTS: During two years' follow-up, 20.7% of the participants developed cognitive impairment. After controlled for age, gender, and plasma homocysteine, a higher level of plasma folate was associated with lower odds of cognitive impairment. The corresponding odds ratio (OR) with 95% confidence interval was 0.41 (0.19-0.89) comparing participants at extreme quintiles of plasma folate (median level 17.2 vs. 6.3 nmol/L). The associations were similar after further adjustment for major demographic and lifestyle factors (OR = 0.42, 0.18-0.98). Moreover, the inverse association was particularly stronger among males (OR = 0.12, 0.03-0.52) but was non-significant among females. CONCLUSION: Our findings support a potential beneficial role of higher plasma folate levels in cognitive function in older Chinese adults, particularly among males. Future studies with larger sample size and longer follow-up are warranted to confirm these findings and to identify the optimal plasma folate level for cognitive function.