An assessment of compositional methods for the analysis of DNA methylation-based deconvolution estimates.

DNA methylation (DNAm)-based deconvolution estimates contain relative data, forming a composition, that standard methods (testing directly on cell proportions) are ill-suited to handle. In this study we examined the performance of an alternative method, analysis of compositions of microbiomes (ANCOM), for the analysis of DNAm-based deconvolution estimates. We performed two different simulation studies comparing ANCOM to a standard approach (two sample t-test performed directly on cell proportions) and analyzed a real-world data from the Women's Health Initiative to evaluate the applicability of ANCOM to DNAm-based deconvolution estimates. Our findings indicate that ANCOM can effectively account for the compositional nature of DNAm-based deconvolution estimates. ANCOM adequately controls the false discovery rate while maintaining statistical power comparable to that of standard methods.

DNA methylation (DNAm)-based deconvolution provides highly accurate estimates of the proportion of each cell type in a mixed-cell type biological sample (e.g., whole-blood). These estimates can be used for examining the association between cell type proportions and biological or clinical end points; for example, comparing the estimated neutrophil proportion in whole blood between smokers and non-smokers. Cell proportion data has unique features which present challenges for traditional and widely used statistical methods. In response to this issue, our work presents two simulation studies and a real-world analysis that benchmark the performance of current standard statistical methods against an alternative method called analysis composition of microbes (ANCOM), which was originally developed for the analysis of microbiome data. In our real-world analysis we used DNAm data collected from Women's Health Initiative Long Life Study I and compared the results of each method against a gold-standard that is typically not available for these analyses. In each of our simulation studies, ANCOM was able to detect true differences in cell proportions between the groups being compared but had a much lower rate of false discovery compared with the standard statistical methods. Our real-world analysis demonstrated similar findings. Overall, our study highlights the potential of ANCOM as a powerful and robust method for analyzing DNAm-derived deconvolution estimates when the interest is comparisons of cell type proportions and biological or clinical end points. ANCOM's ability to minimize false discovery while maintaining robust statistical power positions it as a valuable addition to the epigenomic analysis toolkit.

Explainable AI and transformer models: Unraveling the nutritional influences on Alzheimer's disease mortality.

This pioneering study introduces the use of transformer-based machine learning models and explainable AI approaches to explore the impact of nutrition on Alzheimer's disease (AD) mortality. Using data from the Third National Health and Nutrition Examination Survey (Nhanes iii 1988 to 1994) and the NHANES III Mortality-Linked File (2019) databases, we investigate the intricate relationship between various nutritional factors and AD mortality. Our approach features a novel application of transformer models, which are then benchmarked against established methods like random forests and support vector machines. This comparison not only underscores the strengths of transformer models in handling complex medical datasets but also highlights their potential for providing deeper insights into disease progression. Key findings, such as the significant roles of Platelet distribution width in AD mortality in transformer and Serum Vitamin B12 in random forest, are enhanced by the use of Explainable Artificial Intelligence (XAI), particularly the Shapley Additive Explanations (SHAP) and the integrated gradient methods. This study serves as a vital step forward in applying advanced AI techniques to medical research, offering new perspectives in understanding and combating Alzheimer's Disease.

Association of multiple metabolic and cardiovascular markers with the risk of cognitive decline and mortality in adults with Alzheimer's disease and AD-related dementia or cognitive decline: a prospective cohort study.

Background and objectives: There is a scarcity of data stemming from large-scale epidemiological longitudinal studies focusing on potentially preventable and controllable risk factors for Alzheimer's disease (AD) and AD-related dementia (ADRD). This study aimed to examine the effect of multiple metabolic factors and cardiovascular disorders on the risk of cognitive decline and AD/ADRD. Methods: We analyzed a cohort of 6,440 participants aged 45-84 years at baseline. Multiple metabolic and cardiovascular disorder factors included the five components of the metabolic syndrome [waist circumference, high blood pressure (HBP), elevated glucose and triglyceride (TG) concentrations, and reduced high-density lipoprotein cholesterol (HDL-C) concentrations], C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), factor VIII, D-dimer, and homocysteine concentrations, carotid intimal-medial thickness (CIMT), and urine albumin-to-creatinine ratio (ACR). Cognitive decline was defined using the Cognitive Abilities Screening Instrument (CASI) score, and AD/ADRD cases were classified using clinical diagnoses. Results: Over an average follow-up period of 13 years, HBP and elevated glucose, CRP, homocysteine, IL-6, and ACR concentrations were significantly associated with the risk of mortality in the individuals with incident AD/ADRD or cognitive decline. Elevated D-dimer and homocysteine concentrations, as well as elevated ACR were significantly associated with incident AD/ADRD. Elevated homocysteine and ACR were significantly associated with cognitive decline. A dose-response association was observed, indicating that an increased number of exposures to multiple risk factors corresponded to a higher risk of mortality in individuals with cognitive decline or with AD/ADRD. Conclusion: Findings from our study reaffirm the significance of preventable and controllable factors, including HBP, hyperglycemia, elevated CRP, D-dimer, and homocysteine concentrations, as well as, ACR, as potential risk factors for cognitive decline and AD/ADRD.

Association of type 2 diabetes mellitus with dementia-related and non-dementia-related mortality among postmenopausal women: A secondary competing risks analysis of the women's health initiative.

INTRODUCTION: Alzheimer's disease (AD) and AD-related dementias (ADRD) are leading causes of death among older adults in the United States. Efforts to understand risk factors for prevention are needed. METHODS: Participants (n = 146,166) enrolled in the Women's Health Initiative without AD at baseline were included. Diabetes status was ascertained from self-reported questionnaires and deaths attributed to AD/ADRD from hospital, autopsy, and death records. Competing risk regression models were used to estimate the cause-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for the prospective association of type 2 diabetes mellitus (T2DM) with AD/ADRD and non-AD/ADRD mortality. RESULTS: There were 29,393 treated T2DM cases and 8628 AD/ADRD deaths during 21.6 (14.0-23.5) median (IQR) years of follow-up. Fully adjusted HRs (95% CIs) of the association with T2DM were 2.94 (2.76-3.12) for AD/ADRD and 2.65 (2.60-2.71) for the competing risk of non-AD/ADRD mortality. DISCUSSION: T2DM is associated with AD/ADRD and non-AD/ADRD mortality. HIGHLIGHTS: Type 2 diabetes mellitus is more strongly associated with Alzheimer's disease (AD)/AD and related dementias (ADRD) mortality compared to the competing risk of non-AD/ADRD mortality among postmenopausal women. This relationship was consistent for AD and ADRD, respectively. This association is strongest among participants without obesity or hypertension and with younger age at baseline, higher diet quality, higher physical activity, higher alcohol consumption, and older age at the time of diagnosis of type 2 diabetes mellitus.

Pharmacoepidemiologic study of association between apparent treatment resistant hypertension, cardiovascular disease and interaction effect by sex and age.

BACKGROUND: A limited number of studies have been conducted to test the magnitudes of the association between apparent treatment resistant hypertension (aTRH) and risk of cardiovascular disease (CVD). AIM: To investigate the association between aTRH and risk of CVD and examine whether sex and age modify this association. METHODS: We applied an observational analysis study design using data from the United States Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT recruited participants (n = 25516) from 625 primary care settings throughout the United States, Canada, Puerto Rico, and United States Virgin Islands, aged 55 and older with hypertension and at least one additional risk factor for heart disease. aTRH was assessed from the year 2 visit. CVD event was defined as one of the following from the year 2 follow-up visit: Fatal or non-fatal myocardial infarction, coronary revascularization, angina, stroke, heart failure, or peripheral artery disease. Cox proportional hazards regression was used to examine the effect of aTRH on CVD risk. Potential modifications of sex and age on this association were examined on the multiplicative scale by interaction term and additive scale by joint effects and relative excess risk for interaction. RESULTS: Of the total study participants (n = 25516), 5030 experienced a CVD event during a mean of 4.7 years follow-up. aTRH was associated with a 30% increase in risk of CVD compared to non-aTRH [hazards ratio (HR) = 1.3, 95%CI: 1.19-1.42]. Sex and age modified this relationship on both multiplicative and additive scales independently. Stratified by sex, aTRH was associated with a 64% increase in risk of CVD (HR = 1.64, 95%CI: 1.43-1.88) in women, and a 13% increase in risk of CVD (HR = 1.13, 95%CI: 1.01-1.27) in men. Stratified by age, aTRH had a stronger impact on the risk of CVD in participants aged < 65 (HR = 1.53, 95%CI: 1.32-1.77) than it did in those aged ≥ 65 (HR = 1.18, 95%CI: 1.05-1.32). Significant two-way interactions of sex and aTRH, and age and aTRH on risk of CVD were observed (P < 0.05). The observed joint effect of aTRH and ages ≥ 65 years (HR = 1.85, 95%CI: 1.22-2.48) in males was less than what was expected for both additive and multiplicative models (HR = 4.10, 95%CI: 3.63-4.57 and 4.88, 95%CI: 3.66-6.31), although three-way interaction of sex, age, and aTRH on the risk of CVD and coronary heart disease did not reach a statistical significance (P > 0.05). CONCLUSION: aTRH was significantly associated with an increased risk of CVD and this association was modified by both sex and age. Further studies are warranted to test these mechanisms.

Association between cardiovascular risk and coronavirus disease 2019: findings from 2021 National Health Interview Survey.

PURPOSE: To examine the association between pre-existing cardiovascular disorders and the risk of coronavirus disease 2019 (COVID-19) among community-dwelling adults in the United States. METHODS: We analyzed data from the 2021 National Health Interview Survey, encompassing 28,848 nationally representative participants aged ≥18. We examined the association by two age groups, younger adults (aged 18-59) and older adults (aged ≥60). Weighted analyses were conducted to consider the complex sampling design used in the National Health Interview Survey. RESULTS: The results show that 13.9% of younger and 8.2% of older adults were infected with coronavirus, corresponding to a nationwide estimate of 23,701,358 COVID-19 cases in younger adults and 6310,206 in older adults in 2021. Pre-existing cardiovascular risk factors (overweight, obesity, hypertension, and diabetes) in both age groups and pre-existing cardiovascular diseases (angina, heart attack, and coronary heart disease) in older adults were significantly associated with COVID-19 infection. Significant dose-response relationships existed between increased pre-existing cardiovascular risk factors and COVID-19 infection, with the strongest association in non-Hispanic Black, followed by Hispanic ethnicities and non-Hispanic White. CONCLUSIONS: Pre-existing cardiovascular disorders are significantly associated with the risk of COVID-19 infection. The magnitudes of this risk association are more substantial among minority populations.

Plasma proteins related to inflammatory diet predict future cognitive impairment.

Dysregulation of the immune system and dietary patterns that increase inflammation can increase the risk for cognitive decline, but the mechanisms by which inflammatory nutritional habits may affect the development of cognitive impairment in aging are not well understood. To determine whether plasma proteins linked to inflammatory diet predict future cognitive impairment, we applied high-throughput proteomic assays to plasma samples from a subset (n = 1528) of Women's Health Initiative Memory Study (WHIMS) participants (mean [SD] baseline age, 71.3 [SD 3.8] years). Results provide insights into how inflammatory nutritional patterns are associated with an immune-related proteome and identify a group of proteins (CXCL10, CCL3, HGF, OPG, CDCP1, NFATC3, ITGA11) related to future cognitive impairment over a 14-year follow-up period. Several of these inflammatory diet proteins were also associated with dementia risk across two external cohorts (ARIC, ESTHER), correlated with plasma biomarkers of Alzheimer's disease (AD) pathology (Aß42/40) and/or neurodegeneration (NfL), and related to an MRI-defined index of neurodegenerative brain atrophy in a separate cohort (BLSA). In addition to evaluating their biological relevance, assessing their potential role in AD, and characterizing their immune-tissue/cell-specific expression, we leveraged published RNA-seq results to examine how the in vitro regulation of genes encoding these candidate proteins might be altered in response to an immune challenge. Our findings indicate how dietary patterns with higher inflammatory potential relate to plasma levels of immunologically relevant proteins and highlight the molecular mediators which predict subsequent risk for age-related cognitive impairment.

A meta-analysis on the prevalence of Charcot-Marie-Tooth disease and related inherited peripheral neuropathies.

BACKGROUND: Charcot-Marie-Tooth disease and related inherited peripheral neuropathies (CMT&RIPNs) brings great suffering and heavy burden to patients, but its global prevalence rates have not been well described. METHODS: We searched major English and Chinese databases for studies reporting the prevalence of CMT&RIPNs from the establishment of the databases to September 26, 2022. Based on the age, gender, study design, study region, and disease subtype, the included studies were correspondingly synthesized for meta-analyses on the overall prevalence and/or the subgroup analyses by using pool arcsine transformed proportions in the random-effects model. RESULTS: Of the finally included 31 studies, 21 studied the whole age population and various types of CMT&RIPNs, and the others reported specific disease subtype(s) or adult or non-adult populations. The pooled prevalence was 17.69/100,000 (95% CI 12.32-24.33) for the whole age population and significantly higher for CMT1 [10.61/100,000 (95% CI 7.06-14.64)] than for other subtypes (P' < 0.001). Without statistical significance, the prevalence seemed higher in those aged ≥ 16 or 18 years (21.02/100,000) than in those aged < 16 years (16.13/100,000), in males (22.50/100,000) than in females (17.95/100,000), and in Northern Europe (30.97/100,000) than in other regions. CONCLUSION: CMT&RIPNs are relatively more prevalent as CMT1 in the disease subtypes, and probably prevalent in older ages, males, and Northern Europe. More studies on the epidemiological characteristics of CMT&RIPNs with well-defined diagnosis criteria are needed to improve the prevalence evaluation and to arouse more attention to health care support.

Vitamin d deficiency and metabolic syndrome: The joint effect on cardiovascular and all-cause mortality in the United States adults.

BACKGROUND: The long-term impact of vitamin D deficiency and metabolic syndrome (MetS) on cardiovascular disease (CVD) and all-cause mortality are still a matter of debate. AIM: To test the hypotheses that lower serum 25 hydroxyvitamin D [25(OH)D] concentrations (a marker of vitamin D level) and MetS have a long-term impact on the risk of CVD and all-cause mortality, and individuals with vitamin D deficiency can be identified by multiple factors. METHODS: A sample of 9094 adults, 20 to 90 years of age, who participated in the Third National Health and Nutrition Examination Survey (NHANES III, 1988 to 1994) were followed through December 2015 was analyzed. The associations of serum 25(OH)D concentrations and MetS with CVD and all-cause mortality were analyzed longitudinally using Cox regression models. Classification and regression tree (CART) for machine learning was applied to classify individuals with vitamin D deficiency. RESULTS: Of 9094 participants, 30% had serum 25(OH)D concentrations < 20 ng/mL (defined as vitamin D deficiency), 39% had serum 25(OH)D concentrations between 20 to 29 ng/mL (insufficiency), and 31% had serum 25(OH)D concentrations ≥30 ng/mL (sufficiency). Prevalence of MetS was 28.4%. During a mean of 18 years follow-up, vitamin D deficiency and MetS were significantly associated with increased risk of CVD and all-cause mortality. Subjects with both vitamin D deficiency and MetS had the highest risk of CVD mortality (HR = 1.77, 95%CI: 1.22-2.58) and all-cause mortality (HR = 1.62, 95%CI: 1.26-2.09), followed by those with both vitamin D insufficiency and MetS for CVD mortality (HR = 1.59, 95%CI: 1.12-2.24), and all-cause mortality (HR = 1.41, 95%CI: 1.08-1.85). Meanwhile, vitamin D sufficiency significantly decreased the risk of CVD and all-cause mortality for those who even had MetS. Among the total study sample, CART analysis suggests that being non-Hispanic Black, having lower serum folate level, and being female were the first three predictors for those with serum 25(OH)D deficiency. CONCLUSION: Vitamin D deficiency and MetS were significantly associated with increased risk of CVD and all-cause mortality. There was a significant joint effect of vitamin D deficiency and MetS on the risk of mortality. Findings of the CART analysis may be useful to identify individuals positioned to benefit from interventions to reduce the risk of CVD and all-cause mortality.

Epidemiology for public health practice: The application of spatial epidemiology.

Spatial epidemiology is the description and analysis of geographic patterns and variations in disease risk factors, morbidity and mortality with respect to their distributions associated with demographic, socioeconomic, environmental, health behavior, and genetic risk factors, and time-varying changes. In the Letter to Editor, we had a brief description of the practice for the mortality and the space-time patterns of John Snow's map of cholera epidemic in London, United Kingdom in 1854. This map is one of the earliest public heath practices of developing and applying spatial epidemiology. In the early history, spatial epidemiology was predominantly applied in infectious disease and risk factor studies. However, since the recent decades, noncommunicable diseases have become the leading cause of death in both developing and developed countries, spatial epidemiology has been used in the study of noncommunicable disease. In the Letter, we addressed two examples that applied spatial epidemiology to cluster and identify stroke belt and diabetes belt across the states and counties in the United States. Similar to any other epidemiological study design and analysis approaches, spatial epidemiology has its limitations. We should keep in mind when applying spatial epidemiology in research and in public health practice.

Associations between Circulating SELENOP Level and Disorders of Glucose and Lipid Metabolism: A Meta-Analysis.

Selenoprotein P (SELENOP) is an extracellular antioxidant, selenium transporter, and hepatokine interfering with glucose and lipid metabolism. To study the association between the circulating SELENOP concentration and glucose and lipid metabolic diseases (GLMDs), including gestational diabetes (GD), metabolic syndrome (MetS), non-alcoholic fatty liver disease, obesity, and type 2 diabetes, as well as the individual markers, a meta-analysis was conducted by searching multiple databases from their establishment through March 2022 and including 27 articles published between October 2010 and May 2021, involving 4033 participants. Participants with GLMDs had higher levels of SELENOP than those without GLMDs (standardized mean difference = 0.84, 95% CI: 0.16 to 1.51), and the SELENOP levels were positively correlated with the markers of GLMDs (pooled effect size = 0.09, 95% CI: 0.02 to 0.15). Subgroup analyses showed that the SELENOP concentrations were higher in women with GD and lower in individuals with MetS than their counterparts, respectively. Moreover, SELENOP was positively correlated with low-density lipoprotein cholesterol, but not with the other markers of GLMDs. Thus, the heterogenicity derived from diseases or disease markers should be carefully considered while interpreting the overall positive association between SELENOP and GLMDs. Studies with a larger sample size and advanced design are warranted to confirm these findings.

The association between bilirubin and hypertension among a Chinese ageing cohort: a prospective follow-up study.

BACKGROUND: Hypertension is highly prevalent and associated with the elevated risks of cardiovascular diseases, dementia, and physical disabilities among adults. Although the correlation between bilirubin and hypertension has been reported, the observation in quinquagenarian population is scarce. We aimed to examine bilirubin-hypertension association in Guankou Ageing Cohort Study. METHODS: Participants ≥ 55 years were recruited and their questionnaires and physical examination data were collected. Kaplan-Meier survival analysis and Cox proportional hazards regression were implemented to assess the hypertension risk. The non-liner dose-response relationships of bilirubin-hypertension were determined by restricted cubic spline (RCS) models. Receiver operating characteristic (ROC) curves and multiple factors analysis (MFA) were performed to evaluate the predictive abilities. RESULTS: 1881 eligible participants (male 43.75%, female 56.25%) with the median age of 61.00 (59.00-66.00) were included. The hazard ratio (HR, 95% CI) of serum total bilirubin (STB) and unconjugated bilirubin (UCB) were 1.03 (1.01-1.05) and 1.05 (1.03-1.07), while conjugated bilirubin (CB) showed a weak protective effect with the HR of 0.96 (0.92-0.99), and the associations remained significant in all models. RCS analyses further indicated the similar bidirectional effects of STB and UCB with the cut-off of 12.17 µmol/L and 8.59 µmol/L, while CB exhibited inverse bidirectional dose-response relationship with a cut-off of 3.47 µmol/L. ROC curves and MFA showed baseline STB combined with age, BMI, and waist circumference could well discriminate the low and high of hypertension risk. CONCLUSIONS: Our findings suggested the higher levels of total and unconjugated bilirubin were hazardous factors of hypertension, while an inverse effect presented when more bilirubin was conjugated.

Association between blood pressure levels and cognitive impairment in older women: a prospective analysis of the Women's Health Initiative Memory Study.

BACKGROUND: Whether blood pressure (BP), and at what level of controlled BP, reduces risk of cognitive impairment remains uncertain. We investigated the association of BP and hypertension treatment status with mild cognitive impairment and dementia in older women. METHODS: We prospectively analysed a sample of 7207 community-dwelling women aged 65-79 years participating in the Women's Health Initiative Memory Study (WHIMS). Participants were recruited between May 28, 1996, and Dec 13, 1999, at 39 US clinical centres, and they were followed up until Dec 31, 2019. Cognitive function was assessed annually. Mild cognitive impairment and probable dementia were defined through a centralised adjudication process. BP was measured by trained and certified staff at baseline. Pulse pressure (PP) was calculated as systolic BP (SBP) minus diastolic BP. Hypertension was defined using the American Heart Association 2017 Guideline for High BP in Adults. Outcomes were (1) mild cognitive impairment, (2) probable dementia, and (3) cognitive loss (the combined endpoint of either mild cognitive impairment or probable dementia, or both). We estimated hazard ratios (HRs) to assess the association between hypertension, SBP, and PP with the risk of study outcomes using Cox proportional hazards regression models, with adjustment for key covariates. FINDINGS: During a median follow-up of 9 years (IQR 6-15), 1132 (15·7%) participants were classified as mild cognitive impairment, 739 (10·3%) as probable dementia, and 1533 (21·3%) as cognitive loss. The incidence rates per 1000 person-years were 15·3 cases (95% CI 14·4-16·2) for mild cognitive impairment, 9·7 cases (9·0-10·4) for probable dementia, and 20·3 (19·3-21·3) for cognitive loss. Elevated SBP and PP were significantly associated with increased risk of mild cognitive impairment and cognitive loss (test for trends across SBP and PP strata, p<0·01). Individuals with hypertension, but with controlled SBP of less than 120 mm Hg did not have a significantly increased risk of mild cognitive impairment (HR 1·33, 95% CI 0·98-1·82, p=0·071), and of cognitive loss (1·09, 0·82-1·44, p=0·57) compared with normotension. Individuals on anti-hypertensive treatment with PP of less than 50 mm Hg did not have a significantly higher risk of mild cognitive impairment (1·26, 0·98-1·62, p=0·07) and of cognitive loss (1·17, 0·94-1·46, p=0·16). There were no significant associations between hypertension, SBP, or PP and probable dementia. INTERPRETATION: Results of our study show significant associations of hypertension and elevated SBP and PP levels with risk of mild cognitive impairment and the combined endpoint of either mild cognitive impairment or probable dementia, suggesting that intensive control of hypertension, SBP, and PP can preserve cognitive health in older women. FUNDING: National Heart, Lung, and Blood Institute, National Institutes of Health, and US Department of Health and Human Services.

Association and interaction between dietary patterns and gene polymorphisms in Liangshan residents with hyperuricemia.

Hyperuricemia (HUA) is associated with dietary and genetic factors. However, studies on dietary patterns and their interaction effect with genes on the risk of HUA are limited. We aimed to explore the association between dietary patterns and HUA, and dietary patterns-gene interactions on the risk of HUA. A population-based cross-sectional study was conducted in adults aged 18 and older in Liangshan Yi Autonomous Prefecture of China. Dietary consumption was collected using a standard Food Frequency Questionnaire. Vein blood samples were collected after overnight fasting, and DNA was extracted from peripheral blood leukocytes. Dietary patterns were derived using principal component and factor analysis. Of the 2646 participants, the prevalence of HUA was 26.8%. Three dietary patterns were classified. Of them, a dietary pattern with higher meat consumption (defined as meat-based) had the strongest association with HUA than a dietary pattern with plant-based or local special diet-based. A higher frequency of T allele at ABCG2 rs2231142 and SLC2A9 rs11722228 loci was observed in participants with HUA than those without HUA. An additive interaction of meat-based dietary pattern with rs2231142 locus was significantly associated with an increased risk of HUA. The relative excess risks of interaction, attributable proportion of interaction, and synergy index (S) were 0.482 (95% CI: 0.012-0.976), 0.203 (95% CI: 0.033-0.374), and 1.544 (95% CI: 1.012-2.355), respectively. In conclusion, a dietary pattern with meat-based was significantly associated with an increased risk of HUA. There was an additive interaction between a meat-based dietary pattern and the ABCG2 rs2231142 locus. Individuals with rs2231142 T allele were at higher risk of HUA than those with rs2231142 GG allele.

Dietary sugar intake and risk of Alzheimer's disease in older women.

BACKGROUND: Despite some reports of cardiometabolic disorders associated with the risk of Alzheimer's disease (AD), limited studies have been conducted to examine the association between excessive sugar intake (a risk factor for cardiometabolic disorders) and AD risk. AIM: The purpose of our study was to evaluate if excessive sugar intake has a significant long-term effect on the risk of AD. METHODS: A population sample of 37,689 participants, who enrolled in the United States (US) Women's Health Initiative - Dietary Modification Trial (WHI-DM) in 1993-2005 and its extended observational follow-up study through 1 March 2019, were analyzed. Dietary sugar intake was measured using food frequency questionnaires. AD was classified by reports using a standard questionnaire. A dietary pattern that explained the maxima variations in sugar intake was constructed using reduced rank regression (RRR) technique. Associations of RRR dietary pattern scores and sugar intake (g/day) by quartiles (Q1 through Q4) with AD risk were examined using Cox proportional hazards regression analysis with adjusting for key covariates. RESULTS: During a mean follow-up of 18.7 years, 4586 participants reported having incident AD. The total incidence rate (95% confidence interval [CI]) of AD was 6.5 (6.3-6.7) per 1000 person-years (PYs). The incidence rates (95% CI) of AD by total sugar intake were 6.2 (5.8-6.6), 6.4 (6.0-6.8), 6.6 (6.3-7.0), and 6.9 (6.5-7.3) per 1000 PYs among those in quartiles (Q) 1 to Q4 (toward higher sugar consumption) of total sugar intake, respectively (test for trend of AD incident rates, p < 0.001). Individuals in Q4 of total sugar intake had a 1.19 higher risk of incident AD than those in Q1 (hazard ratio [HR] = 1.19, 95% CI: 1.05-1.34, p = 0.01). An estimated increase of 10 g/day in total sugar intake (about 2.4 teaspoons) was associated with an increased AD risk by 1.3-1.4%. Of six subtypes of sugar intake, lactose was significantly associated with AD risk. CONCLUSIONS: Our study indicates that excessive total sugar intake was significantly associated with AD risk in women. Of six subtypes of sugar intake, lactose had a stronger impact on AD risk.

Associations of time-varying obesity and metabolic syndrome with risk of incident heart failure and its subtypes: Findings from the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: Most previous studies have examined associations between metabolic disorders measured at a single point in time and risk of heart failure (HF). However, there are many situations where the values of exposures vary over time before HF occurs. We aimed to examine the associations of time-varying obesity and metabolic syndrome (MetSyn) measured at multiple points in time with HF. METHODS: A total of 6750 participants in the Multi-Ethnic Study of Atherosclerosis from 2000 were included in the study. Follow-up was completed through December 2015. MetSyn was defined using the American Heart Association criteria. Incident HF was diagnosed by clinical criteria. Subtypes HF (reduced ejection fraction (HFrEF) and preserved (HFpEF) were classified by left ventricular EF. RESULTS: A total of 331 HF cases were identified during 82,609 person-years of observation. The incidence (95%CI) of total HF was 4.0 (3.4-4.4) per 1000 person-years. Of the total HF cases, 45.6% were HFrEF (n = 151), 40.8% HFpEF (n = 135), and 13.6% were unclassified HF subtypes (n = 45). After adjusting for key covariates, time-varying obesity (BMI ≥ 30 kg/m2) and MetSyn were significantly associated with HF, with a stronger association for HFpEF than for HFrEF. The corresponding hazards ratios (HR, 95%CI) were 1.97 (1.43-2.72) and 1.86 (1.43-2.42) for HFpEF, and 1.46 (1.07-1.98), and 1.39 (1.06-1.82) for HFrEF respectively. Time-varying large waist circumference was significantly associated with for HFpEF, but not with HFrEF. CONCLUSION: Time-varying obesity and MetSyn were significantly associated with HF risk, with a stronger association with HFpEF than with HFrEF. Continued effort to control these risk factors is recommended.

Impact of diabetes mellitus and cardiometabolic syndrome on the risk of Alzheimer's disease among postmenopausal women.

BACKGROUND: In spite of an increase in the incidence and prevalence of diabetes mellitus (DM) and Alzheimer's disease (AD) in the aging population worldwide, limited attention has been paid to their potential association. AIM: To investigate the association of DM and cardiometabolic syndrome (CMS, a precursor to DM) with risk of incident AD among postmenopausal women. METHODS: Postmenopausal women aged 50-79 (n = 63117) who participated in the U.S. Women's Health Initiative Observational Study (WHIOS), recruited in 1993-1998, without baseline AD and followed up through March 1, 2019, were analyzed. AD was classified by participant-reported history of doctor-diagnosis of incident AD in the WHIOS. DM was defined by participant-report or treated because of diabetes or serum glucose concentrations ≥ 126 mg/dL. CMS was defined as having ≥ 3 of five CMS components: large waist circumference, high blood pressure, elevated triglycerides, elevated glucose, and low high-density lipoprotein cholesterol. The associations of DM and CMS with AD were analyzed using Cox's proportional hazards regression analysis. RESULTS: During a median follow-up of 20 years (range: 3.36 to 23.36 years), of 63117 participants, 8340 developed incident AD. Women with DM had significantly higher incidence of AD [8.5, 95% confidence interval (CI): 8.0-9.0 per 1000 person-years (PY)] than those without DM (7.1, 95%CI: 6.9-7.2 per 1000 PY). Multivariate Cox's regression analysis indicated that women with DM or CMS had a significantly higher risk of AD than those without DM or CMS. The corresponding hazard ratios [HR (95%CI)] were 1.22 (1.13-1.31, P < 0.001) in subjects with DM, and 1.18 (1.09-1.27, P < 0.001) in subjects with CMS. The HRs diminished with age and became non-significant in the oldest age group. CONCLUSION: During a median follow-up of 20 years, DM and CMS were significantly associated with the risk of AD among postmenopausal women. More specifically, women aged 50-69 with DM or CMS vs those without these conditions had significantly higher relative risks of AD than the relative risks of AD in those aged 70-79 with DM or CMS vs those without DM or CMS.

Associations between metabolic syndrome and four heavy metals: A systematic review and meta-analysis.

Four most concerned heavy metal pollutants, arsenic, cadmium, lead, and mercury may share common mechanisms to induce metabolic syndrome (MetS). However, recent studies exploring the relationships between MetS and metal exposure presented inconsistent findings. We aimed to clarify the relationship between heavy metal exposure biomarkers and MetS using a meta-analysis and systematic review approach. Literature search was conducted in international and the Chinese national databases up to June 2020. Of selected studies, we extracted the relevant data and evaluated the quality of each study's methodology. We then calculated the pooled effect sizes (ESs), standardized mean differences (SMDs), and their 95% confidence intervals (CIs) using a random-effect meta-analysis approach followed by stratification analyses for control of potential confounders. Involving 55,536 participants, the included 22 articles covered 52 observational studies reporting ESs and/or metal concentrations on specific metal and gender. Our results show that participants with MetS had significantly higher levels of heavy metal exposure [pooled ES = 1.16, 95% CI: 1.09, 1.23; n = 42, heterogeneity I2 = 75.6%; and SMD = 0.22, 95% CI: 0.15, 0.29; n = 32, I2 = 94.2%] than those without MetS. Pooled ESs in the subgroups stratified by arsenic, cadmium, lead, and mercury were 1.04 (95% CI: 0.97, 1.10; n = 8, I2 = 61.0%), 1.10 (0.95, 1.27; 11, 45.0%), 1.21 (1.00, 1.48; 12, 82.9%), and 1.26 (1.06, 1.48; 11, 67.7%), respectively. Pooled ESs in the subgroups stratified by blood, urine, and the other specimen were 1.22 (95% CI: 1.08, 1.38; n = 26, I2 = 75.8%), 1.06 (1.00, 1.13; 14, 58.1%), and 2.41 (1.30, 4.43; 2, 0.0%), respectively. In conclusion, heavy metal exposure was positively associated with MetS. Further studies are warranted to examine the effects of individual metals and their interaction on the relationship between MetS and heavy metals.

Epidemiology of Cancers in Zambia: A significant variation in Cancer incidence and prevalence across the nation.

BACKGROUND: Cancer is one of the leading causes of death worldwide. More than two-thirds of deaths due to cancers occur in low- and middle-income countries where Zambia belongs. This study, therefore, sought to assess the epidemiology of various types of cancers in Zambia. METHODS: We conducted a retrospective observational study using the Zambia National Cancer Registry (ZNCR) population based data from 2007 to 2014. Zambia Central Statistics Office (CSO) demographic data were used to determine catchment area denominator used to calculate prevalence and incidence rates of cancers. Age-adjusted rates and case fatality rates were estimated using standard methods. We used a Poisson Approximation for calculating 95% confidence intervals (CI). RESULTS: The seven most cancer prevalent districts in Zambia were Luangwa, Kabwe, Lusaka, Monze, Mongu, Katete and Chipata. Cervical cancer, prostate cancer, breast cancer and Kaposi's sarcoma were the four most prevalent cancers as well as major causes of cancer related deaths in Zambia. Age adjusted rates and 95% CI for these cancers were: cervix uteri (186.3; CI = 181.77 - 190.83), prostate (60.03; CI = 57.03 - 63.03), breast (38.08; CI = 36.0 - 40.16) and Kaposi's sarcoma (26.18; CI = 25.14 - 27.22). CFR were: Leukaemia (38.1%); pancreatic cancer (36.3%); lung cancer (33.3%); and brain, nervous system (30.2%). The cancer population was associated with HIV with p-value of 0.000 and a Pearson correlation coefficient of 0.818. CONCLUSIONS: The widespread distribution of cancers with high prevalence observed in the southern zone may have been perpetrated by lifestyle and sexual culture (traditional male circumcision known to prevent STIs is practiced in the northern belt) as well as geography. Intensifying cancer screening and early detection countrywide as well as changing the lifestyle and sexual culture would greatly help in the reduction of cancer cases in Zambia.