The relationship between uric acid and brain health from observational studies.

This study conducts a systematic literature review and meta-analysis regarding the potential influence of serum uric acid levels on cerebral small vessel diseases and the cognitive status in the prodromal stages of dementia. We identified four different cerebral small vessel diseases and three specific domains of cognitive performance to be considered in the literature search. The analysis contained 14 studies (13 cross-sectional design and one longitudinal design) with 11,502 participants measuring the relationship between uric acid and cerebral small vessel disease. In both continuous and categorical analyses, significant associations were found between hyperuricemia and cerebral small vessel diseases (continuous data: pooled OR: 1.00, 95%CI: 1.00-1.01 and categorical data: pooled OR: 1.42, 95%CI: 1.15-1.75). For the relationship between uric acid and cognitive performance, 19 studies with 49,901 participants were considered, including eight cohort studies, and 11 cross-sectional studies. The cross-sectional data showed that a marginal relationship existed between uric acid and global cognition (ß: 0.00, 95%CI: -0.01-0.00). The pooled analysis of cohort studies indicated that higher uric acid had a deleterious effect on attention and executive function (continuous data: ß: -0.02, 95%CI: -0.04-0.00 and categorical data: ß: -0.03, 95%CI: -0.07-0.00). Conclusion: Our study indicated that a higher level of uric acid had an adverse effect on brain health. Furthermore, a high level of uric acid is related to cognitive decline in attention and executive function, which may exist a long time before the diagnosis of dementia.

Prediabetes and structural brain abnormalities: Evidence from observational studies.

Type 2 diabetes mellitus has been linked to structural brain abnormalities, but evidence of the association among prediabetes and structural brain abnormalities has not been systematically evaluated. Comprehensive searching strategies and relevant studies were systematically retrieved from PubMed, Embase, Medline and web of science. Twelve articles were included overall. Stratified analyses and regression analyses were performed. A total of 104 468 individuals were included. The risk of infarct was associated with continuous glycosylated haemoglobin (HbA1c ) [adjusted odds ratio (OR) 1.19 (95% confidence interval [CI]: 1.05-1.34)], or prediabetes [adjusted OR 1.13 (95% CI: 1.00-1.27)]. The corresponding ORs associated with white matter hyperintensities were 1.08 (95%CI: 1.04-1.13) for prediabetes, and 1.10 (95%CI: 1.08-1.12) for HbA1c . The association was significant between the decreased risk of brain volume with continuous HbA1c (the combined OR 0.92, 95% CI: 0.87-0.98). Grey matter volume and white matter volume were inversely associated with prediabetes [weighted mean deviation (WMD), -9.65 (95%CI: -15.25 to -4.04) vs WMD, -9.25 (95%CI: -15.03 to -3.47)]. There were no significant association among cerebral microbleeds, hippocampal volume, continuous total brain volume, and prediabetes. Our findings demonstrated that (a) both prediabetes and continuous HbA1c were significantly associated with increasing risk of infarct or white matter hyperintensities; (b) continuous HbA1c was associated with a decreased risk of brain volume; (c) prediabetes was inversely associated with grey matter volume and white matter volume. To confirm these findings, further studies on early diabetes onset and structural brain abnormalities are needed.

Urine NGAL as an early biomarker for diabetic kidney disease: accumulated evidence from observational studies.

Objectives: Urine neutrophil gelatinase-associated lipocalin (NGAL) was found to increase in diabetic kidney disease (DKD). However, the clinical value of urine NGAL as diagnostic indicators in DKD remains to be clarified. Methods: Relevant studies were systematically retrieved from PubMed, Embase, Web of Science, and the Cochrane Library. Stratified analyses and regression analyses were performed. Results: Fourteen studies with 1561 individuals were included in our analysis, including 1204 cross-sectional participants and 357 cohort participants. For the cross-sectional studies, the pooled sensitivity and specificity of NGAL in the diagnosis of DKD were 0.82 (95% confidence interval (CI): 0.75-0.87) and 0.81 (95% CI: 0.68-0.90), respectively. The pooled diagnostic odds ratio was 19 (95% CI: 11-33), and the overall area under the curve was 0.88 (95% CI: 0.84-0.90). For the cohort studies, the pooled sensitivity and specificity of NGAL in the diagnosis of DKD were 0.96 (95% CI: 0.91-0.98) and 0.89 (95% CI: 0.84-0.92), respectively. The overall area under the curve was 0.98, indicating good discriminative ability of NGAL as biomarkers for DKD. Conclusions: Urine NGAL, as the early diagnostic marker of DKD, might have the high diagnostic value, especially in cohort studies.

The association between weight change patterns and obesity-related complex multimorbidity: evidence from NHANES.

Objective: Obesity is a major risk factor for non-communicable diseases (NCDs), which has been the leading cause of death nowadays. The aim of this study is to examine the association between total changes in body mass index (BMI) across adulthood and the risk of obesity-related complex multimorbidity in elderly, characterizing the capacity of BMI waves in predicting major chronic diseases. Methods: In this retrospective study, 15,520 participants were analyzed from the National Health and Nutrition Examination Survey (NHANES) from 1999 and 2018. BMI was categorized as obesity (≥30.0 kg/m²), overweight (25.0-29.9 kg/m²), normal weight (18.5-24.9 kg/m²), and underweight (<18.5 kg/m²). Odds ratios (ORs) with 95% confidence interval (CIs) for the relationship between BMI change patterns and major health outcomes included hypertension, cancer, chronic obstructive pulmonary disease, cardiovascular disease, and diabetes, and population attributable fractions (PAFs) of BMI were evaluated. Results: In comparison with participants who remained non-obese, those who are stable obese showed the highest risks of developing at least one chronic disease in later life, with odds ratios of 2.76 (95% CI: 2.20 to 3.45) from age 25 years to 10 years before baseline, 2.90 (2.28 to 3.68) from age 25 years to baseline, and 2.49 (2.11 to 2.95) in the 10-year period before baseline. Moving from non-obese to obese weight-change pattern in all periods (from age 25 years to 10 years before baseline: OR = 1.82; 95% CI, 1.57 to 2.11; from age 25 years to baseline: OR = 1.87; 95% CI, 1.59 to 2.19; from 10 years before baseline to baseline: OR = 1.62; 95% CI, 1.26 to 2.08) and moving from obese to non-obese, the 10-year period before baseline (OR = 1.89; 95% CI, 1.39 to 2.57) was associated with increased risk of chronic diseases. Midlife obesity status can explain the 8.6% risk of occurrence of the chronic diseases in elderly. Conclusions: Maintaining a stable healthy weight and losing weight in early adulthood and midlife are important for better life quality during the aging process. More effective strategies and policies to reduce the prevalence of obesity are needed.

Validation of a new portable system containing both FeNO analysis and spirometry measurement.

Introduction: Pulmonary function tests and FeNO measurements are widely used for the diagnosis and management of respiratory diseases. They are used to evaluate airway limitation and respiratory inflammation. Standard spirometers and nitric oxide (NO) analyzers are widely used in hospitals. However, their high price has made some hospitals in underdeveloped areas unable to afford or purchase these devices. The development of a new portable system (SUNVOU TM2125) combining FeNO measurement and spirometry provides additional possibilities for optimizing the diagnosis and management of respiratory diseases. However, its accuracy needs further validation. Methods: The FeNO analysis component of SUNVOU TM2125 was compared with that of a widely used NO analyzer (NIOX VERO). The spirometry component of the TM2125 was compared with a standard spirometer (Jaeger MasterScreen) for pulmonary parameters such as FEV1, FVC, FEV1/FVC, and PEF. Pearson correlation and Bland-Altman plots were used to evaluate the agreement between the devices. Results: FeNO values measured using TM2125 were higher than those measured using VERO, with a mean difference of 1.8 ppb. There was a strong correlation between FeNO values measured using the two devices (r = 0.988, p < 0.001). Bland-Altman plots showed a high degree of agreement between the two devices, with 93.3% of values within the 95% confidence interval range. The spirometric parameters (FEV1, FVC, FEV1/FVC, and PEF) measured using the TM2125 were lower than those measured using the MasterScreen. Good correlations were observed between the values measured using the TM2125 and MasterScreen (r > 0.9). Based on the Bland-Altman plots, there was a high degree of agreement between the devices. Conclusion: The accuracy of FeNO and spirometry measurements using SUNVOU TM2125 was validated. This can help improve the diagnosis and monitoring of chronic respiratory diseases in underdeveloped countries.

The Association Between Diabetes Duration and Domain-Specific Cognitive Impairment: A Population-Based Study.

BACKGROUND: Diabetes is a risk factor for cognitive impairment, and disease duration is associated with geriatric decline and functional disabilities. OBJECTIVE: This study aimed to examine the association of diabetes duration with domain-specific cognitive impairment in elderly. METHODS: A total of 3,142 participants from the National Health and Nutrition Examination Survey (NHANES) from the period between 2011 and 2014 were included. We assessed cognitive function using the Digit Symbol Substitution Test (DSST), the CERAD Word Learning (CERAD-WL) test, the CERAD Delayed Recall (CERAD-DR) test and animal fluency (AF) test. RESULTS: After adjusting for age, sex, race/ethnicity, education level, and annual household income, we found that diabetes with a duration longer than 20 years were at 3.32-fold increased risk of DSST impairment (OR = 3.32, 95% CI: 1.95 to 5.67), 1.72-fold increased risk of CERAD-WL impairment (OR = 1.72, 95% CI: 1.13 to 2.62), and 1.76-fold increased risk of AF impairment (OR = 1.76, 95% CI: 1.23 to 2.53), compared with those with no diabetes. Associations were generally stronger in women than in men. Participants with diabetes, who were diagnosed at 50-59 years old were at increased risk of DSST impairment, CERAD-WL impairment, CERAD-DR impairment, and AF impairment per 5 years longer duration of diabetes. CONCLUSION: Longer diabetes duration was associated with the increased risk of cognitive impairment, especially in processing speed and attention. The presence of chronic kidney disease was associated with the increased risk of DSST impairment.

Relationship Between Weight-Change Patterns and Cognitive Function: A Retrospective Study.

BACKGROUND: Obesity has been linked to cognitive impairment. However, how changes in body mass index (BMI) over the life course influence cognitive function remains unclear. OBJECTIVE: The influence of distinct weight-change patterns from young adulthood to midlife and late adulthood on cognitive function in older adults was explored. METHODS: A total of 5,809 individuals aged≥60 years were included and categorized into four groups on the basis of BMI change patterns. Cognitive function was assessed using four cognition tests in the baseline survey. The relationship between the weight-change patterns and cognition was evaluated using regression models. RESULTS: In comparison with participants who remained at non-obese, those moving from the non-obese to obese weight-change pattern from young (25 years of age) to middle adulthood showed lower Digit Symbol Substitution Test (DSST) scores (ß= -1.28; 95% confidence interval [CI]: -2.24 to -0.32). A non-obese to obese change pattern from age 25 years of age to 10 years before baseline was associated with a higher risk of DSST impairment (odds ratio = 1.40; 95% CI: 1.09 to 1.79). In comparison with participants whose heaviest weight was recorded after 60 years of age, those with the heaviest weight between 18 and 40 years of age had lower DSST scores (ß= -1.46; 95% CI: -2.77 to -1.52). CONCLUSION: Our results suggest that the transition from the non-obese to obese category in early adulthood and appearance of the heaviest weight between 18 and 40 years of age are associated with lower cognitive function in later life.

Predicted lean body mass in relation to cognitive function in the older adults.

Background: Previous findings about lean body mass (LBM) and cognitive function remain unclear. We aimed to examine this association by using data from the National Health and Nutrition Examination Survey (NHANES). Methods: Using data from the NHANES 2011-2014, we conducted logistic regression models to investigate the relation between the predicted LBM and domain-specific cognitive function assessed by Digit Symbol Substitution Test (DSST), Consortium to Establish a Registry for Alzheimer's Disease Word Learning test (CERAD-WL) and Delayed Recall test (CERAD-DR), and Animal Fluency (AF) for information processing speed, memory, and executive function, respectively. Cognitive impairment was defined as the lowest quartile of each cognitive test in the total population. Sex-stratified analysis was further made. Results: A total of 2955 participants aged 60 and above (mean [SD] age, 69.17[0.20] years; 1511 female [51.13%]) were included in the study. After being adjusted for social economic factors, anthropometric parameters, and diseases, we found a positive association between predicted LBM and information processing speed (Odds ratio of DSST impairment= 0.95, 95%CI= 0.91 to 0.99) regardless of body mass index and sex. Compared with patients in the first quartile of predicted LBM, those in the fourth quartile had an odds ratio of 0.355 (95% confidence interval 0.153-0.822) for DSST impairment. No significant relation in other cognitive tests and predicted LBM was found whether stratified by sex or not. Conclusion: Our findings point to the association between predicted lean body mass and cognitive dysfunction in information processing speed, which could be used for early detection and prevention of deterioration of cognitive function among older adults.

Bloom of tetracycline resistance genes in mudflats following fertilization is attributed to the increases in the shared potential hosts between soil and organic fertilizers.

A field experiment was carried out in mudflats adjacent to the Yellow Sea, China, amended with sewage sludge and vermicompost by one-time input at different rates to reveal the fates of tetracycline resistance genes (TRGs) and their potential hosts in the soils. Quantitative PCR results showed that soils added with either sludge or vermicompost had more abundant TRGs compared with the non-fertilized soil. This situation was more obvious in sludge fertilized soils especially at high application rates. Vermicompost exhibited a promising outlook for improvement of the mudflats. The abundances of intI1 in the non-fertilized soils were significantly higher than those in fertilizers and fertilized soils. The potential hosts for intI1 were not shared with other TRGs-contained hosts, indicating that intI1 had little effects on the dissemination of TRGs in the mudflats. Moreover, the exclusive hosts for TRGs in fertilizers were not higher than those in the non-fertilized soils, illustrating little effects of fertilization on the introduction of exogenous TRGs into soil. The shared hosts between soil and fertilizers were highest among four possible sources, contributing vastly to the bloom of TRGs following fertilization. It was also shown that different organic fertilizers caused distinct categories of shared potential hosts for TRGs. RDA analysis further indicated that the abundances of the shared potential hosts were affected by soil nutrients. These results suggested that the development of TRGs in soil following fertilization depended on the shared potential hosts with similar ecological niches between soil and fertilizers.

The Relationship Between BMI and Lung Function in Populations with Different Characteristics: A Cross-Sectional Study Based on the Enjoying Breathing Program in China.

Purpose: To analyze the relationship between body mass index (BMI) and lung function, which may help optimize the screening and management process for chronic obstructive pulmonary disease (COPD) in the early stages. Patients and Methods: In this cross-sectional study using data from the Enjoying Breathing Program in China, participants were divided into two groups according to COPD Screening Questionnaire (COPD-SQ) scores (at risk and not at risk of COPD) and three groups based on lung function (normal lung function, preserved ratio impaired spirometry [PRISm], and obstructive lung function). Results: A total of 32,033 subjects were enrolled in the current analysis. First, in people at risk of COPD, overweight and obese participants had better forced expiratory volume in one second (FEV1; overweight: 0.33 liters (l), 95% confidence interval [CI]: 0.27 to 0.38; obesity: 0.31 L, 95% CI: 0.22 to 0.39) values than the normal BMI group. Second, among people with PRISm, underweight participants had a lower FEV1 (-0.56 L, 95% CI: -0.86 to -0.26) and forced vital capacity (FVC; -0.33 L, 95% CI: -0.55 to -0.11) than participants with a normal weight, and obese participants had a higher FEV1 (0.22 L, 95% CI: 0.02 to 0.42) and FVC (0.16 L, 95% CI: 0.02 to 0.30) than participants with a normal weight. Taking normal BMI as the reference group, lower FEV1 (-0.80 L, 95% CI: -0.97 to -0.63) and FVC (-0.53 L, 95% CI: -0.64 to -0.42) were found in underweight participants with obstructive spirometry, and better FEV1 (obesity: 0.26 L, 95% CI: 0.12 to 0.40) was found in obese participants with obstructive spirometry. Conclusion: Being underweight and severely obese are associated with reduced lung function. Slight obesity was shown to be a protective factor for lung function in people at risk of COPD and those with PRISm.

Association of Sarcopenia and A Body Shape Index With Overall and Cause-Specific Mortality.

Aim: This observational study aimed to examine the association between the A Body Shape Index (ABSI) and/or sarcopenia and total, cardiovascular, and cancer mortality. Methods: The associations of sarcopenia and ABSI with all-cause, cardiovascular, and cancer mortality were assessed in 4,488 participants from the 1999-2004 National Health and Nutrition Examination Survey (NHANES) who were followed up until December 31, 2015. Models were analyzed separately for men and women and adjusted for age, race, and other confounding factors. ABSI was assessed as a continuous measurement by quartile for men and women. Population attributable fractions (PAFs) were calculated to assess mortality caused by sarcopenia and/or ABSI in the study population. Results: When ABSI was assessed as a continuous variable, the ABSI quartile showed a linear trend for total (p = 0.0001), cardiovascular (p = 0.04), and cancer (p = 0.02) mortality in men and for total (p = 0.06) and cardiovascular (p = 0.06) mortality in women. The hazard ratios (HRs) of the fourth ABSI quartile were 1.51 [95% confidence interval (CI): 1.20-1.89] in men and 1.23 (95% CI: 0.93-1.64) in women, compared with those in the first quartile. When ABSI was assessed by quartile, the appendicular skeletal mass index (ASMI) was lower in the groups with high ABSI. When high ABSI was combined with sarcopenia, the HRs of all-cause mortality were 2.05 (95% CI: 1.60-2.62) in men and 1.51 (95% CI: 1.19-1.92) in women. In the subpopulation (sarcopenia group or higher ABSI), the PAFs of mortality due to sarcopenia were 26.16% (95% CI: 12.68-37.56) in men and 21.89% (95% CI: 5.64-35.35) in women, and the PAF of mortality due to higher ABSI was 23.70% (95% CI: 12.11-33.77) in men. Conclusion: The ABSI value was significantly associated with all-cause and cardiovascular mortality, and the co-existence of higher ABSI values and sarcopenia can contribute to a more significant death risk in comparison with high ABSI values or sarcopenia. Moreover, the ABSI values in combination with the ASMI can be used to preliminarily evaluate the content and distribution of fat and muscle and to predict the risk of death in obese and sarcopenic populations.

Association of kidney function and brain health: A systematic review and meta-analysis of cohort studies.

OBJECTIVE: This study aimed to evaluate the bidirectional association between the kidney dysfunction and the brain health, including structural and functional abnormalities. DESIGN: Systematic review and meta-analysis with network meta-analysis for outcomes with different estimated glomerular filtration rate (eGFR) ranges. DATA SOURCES: PubMed, Embase database, Cochrane library and Web of Science (up to Dec. 2021). ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Longitudinal studies that provided evidence of the impact of kidney function estimated from eGFR and urine albumin-to-creatinine ratio (UACR) or chronic kidney disease (CKD) on structural and functional brain abnormalities, and those that provided evidence of the opposite relationship. Studies with study population mean age under 18 years old were excluded. MAIN OUTCOME MEASURES: Two independent reviewers screened the included studies, extracted the data, and assessed the risk of bias. We performed a random-effects meta-analysis and a network meta-analysis for outcomes with compatible data. We assessed the risk of bias using the Newcastle-Ottawa Quality Assessment Scale criteria (NOS). Subgroup and sensitivity analyses were conducted to explore heterogeneity in the meta-analyses. Inconsistency analyses using the node-splitting method were performed to confirm the results of network meta-analysis. RESULTS: A total of 53 studies with 3037,357 participants were included in the current systematic review. Among these, 16 provided evidence of structural brain abnormalities, and 38 provided evidence of cognitive impairment and dementia. Analysis of evidence of categorical kidney function showed a positive association between kidney dysfunction and cerebral small vessel disease (cSVD) (relative risk (RR) 1.77, 95% confidence interval (CI) 1.40-2.24, I2 = 0.0%), but such results were not found in the analyses of evidence where the kidney function was measured as a continuous variable. Meanwhile, analysis of 28 prior longitudinal studies with 194 compatible sets of data showed that the worse kidney function as categorical variables was related to a greater risk of global brain cognitive disorder (RR 1.28, 95% CI 1.20-1.36, I2 = 82.5%). CONCLUSIONS: In this systematic review and meta-analysis, we found a positive association between CKD and functional brain disorders. However, the relationship between the kidney dysfunction and structural abnormalities in the brain remains controversial. As for the opposite relationship, structural brain abnormalities, especially cerebral microbleeds and silent infarction, but not functional brain abnormalities, are associated with worse renal function. In addition, a higher UACR, but not a lower eGFR, was associated with a higher risk of Alzheimer's disease and vascular dementia.

Cerebral Blood Flow Alterations and Obesity: A Systematic Review and Meta-Analysis.

BACKGROUND: Reduction in cerebral blood flow (CBF) plays an essential role in the cognitive impairment and dementia in obesity. However, current conclusions regarding CBF changes in patients with obesity are inconsistent. OBJECTIVE: A systematic review and meta-analysis was performed to evaluate the relationship between obesity and CBF alterations. METHODS: We systematically screened published cross-sectional and longitudinal studies focusing on the differences in CBF between obese and normal-weight individuals. Eighteen studies including 24,866 participants, of which seven articles reported longitudinal results, were evaluated in the present study. RESULTS: The results of the meta-analysis showed that in cross-sectional studies, body mass index (BMI) was negatively associated with CBF (ß= -0.31, 95% confidence interval [CI]: -0.44, -0.19). Moreover, this systematic review demonstrated that obese individuals showed global and regional reductions in the CBF and increased CBF in diverse functional areas of the frontal lobe, including the prefrontal cortex, left frontal superior orbital, right frontal mid-orbital cortex, and left premotor superior frontal gyrus. CONCLUSION: Our findings suggest that BMI, rather than waist circumference and waist-to-hip ratio, is inversely associated with CBF in cross-sectional studies. The CBF of obese individuals showed global and regional reductions, including the frontal lobe, temporal and parietal lobes, cerebellum, hippocampus, and thalamus.

Impact of Intensive Glucose Control on Brain Health: Meta-Analysis of Cumulative Data from 16,584 Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: Despite growing evidence that type 2 diabetes is associated with dementia, the question of whether intensive glucose control can prevent or arrest cognitive decline remains unanswered. In the analysis reported here, we explored the effect of intensive glucose control versus standard care on brain health, including structural abnormalities of the brain (atrophy, white matter hyperintensities, lacunar infarction, and cerebral microbleeds), cognitive dysfunction, and risk of dementia. METHODS: We searched the PubMed and Embase databases, the Web of Science website, and the Clinicaltrial.gov registry for studies published in English prior to July 2020. Only studies with a randomized controlled trial (RCT) design were considered. We analyzed structural abnormalities of the brain (atrophy, white matter hyperintensities, lacunar infarction, and cerebral microbleeds), cognitive function (cognitive impairment, executive function, memory, attention, and information-processing speed), and dementia (Alzheimer's disease, vascular dementia, and mixed dementia). RESULTS: Six studies (5 different RCTs) with 16,584 participants were included in this meta-analysis. One study that compared structural changes between groups receiving intensive versus conventional glucose control measures reported non-significant results. The results of the five studies, comprising four cohorts, indicated a significantly poorer decline in cognitive function in the intensive glucose control group (ß - 0.03, 95% confidence interval [CI] - 0.05 to - 0.02) than in the conventional glucose control group. Further subgroup analysis showed a significant difference in the change in cognitive performance in composite cognitive function (ß - 0.03, 95% CI - 0.05 to - 0.01) and memory (ß - 0.13, 95% CI - 0.25 to - 0.02). One trial evaluated the prevalence of cognitive impairment and dementia between groups receiving intensive and conventional glucose control, respectively, and the differences were insignificant. CONCLUSION: This meta-analysis suggests that intensive glucose control in patients with type 2 diabetes can slow down cognitive decline, especially the decline in composite cognition and memory function. However, further studies are necessary to confirm the impact of strict glucose control on structural abnormalities in the brain and the risk of dementia.

The changes in antibiotic resistance genes during 86 years of the soil ripening process without anthropogenic activities.

This study aimed to reveal the baseline of natural variations in antibiotic resistance genes (ARGs) in soil without anthropogenic activities over the decades. Nine soil samples with different time of soil formation were taken from the Yancheng Wetland National Nature Reserve, China. ARGs and mobile genetic elements (MGEs) were characterized using metagenomic analysis. A total of 196 and 192 subtypes of ARGs were detected in bulk soil and rhizosphere, respectively. The diversity and abundance of ARGs were stable during 69 years probably due to the alkaline pH soil environment but not due to antibiotics. Increases in ARGs after 86 years were probably attributed to more migrant birds inhabited compared with other sampling sites. Multidrug was the most abundant type, and largely shared by soil samples. It was further shown that soil samples could not be clearly distinguished, suggesting a slow process of succession of ARGs in the mudflat. The variation partitioning analysis revealed that the ARG profile was driven by the comprehensive effects exhibited by the bacterial community, MGEs, and environmental factors. Besides, pathogenic bacteria containing ARGs mediated by migrant birds in the area with 86 years of soil formation history nearing human settlements needed special attention. This study revealed the slow variations in ARGs in the soil ripening process without anthropogenic activities over decades, and it provided information for assessing the effect of human activities on the occurrence and dissemination of ARGs.

Spectrum of thyroid dysfunction and dementia: a dose-response meta-analysis of 344,248 individuals from cohort studies.

Thyroid hormone, as a modifiable risk factor for dementia, promotes neurocognitive function and regulates metabolic processes. Various studies have defined different thyroid-stimulating hormone cutoffs, but the safest thyroid-stimulating hormone concentration was absent. A dose-response meta-analysis describing the overall functional relation and identifying exposure intervals associated with a higher or lower disease risk is thus desirable. Therefore, our current analysis was conducted to understand the influence of thyroid dysfunction on dementia risk. We searched PubMed, Embase, and Web of Science before May 1, 2020 for human studies published in English. Studies were considered for inclusion if they used a cohort study design to measure the risk of dementia in different thyroid function status groups, diagnosed thyroid functional status and all-cause dementia, included participants aged >18 years, and provided quantitative measures of data. The analysis contained 17 articles with 344,248 individuals with a 7.8-year mean follow-up. Ten studies with 329,287 participants indicated that only subclinical hyperthyroidism was associated with an increased risk of dementia. In contrast, subclinical hypothyroidism, clinical hyperthyroidism, and clinical hypothyroidism did not affect dementia. In the dose-response meta-analysis with 46,417 samples from 11 studies, the association of thyroid-stimulating hormone with the risk of dementia exhibited a U-shaped curve. Our study indicated that subclinical hyperthyroidism was associated with the risk of dementia and the thyroid-stimulating hormone concentration at around 1.55-1.60 mU/L as the optimum range for the risk of dementia.

Relationship between obesity and structural brain abnormality: Accumulated evidence from observational studies.

We aimed to evaluate the relationship between obesity and structural brain abnormalities assessed by magnetic resonance imaging using data from 45 observational epidemiological studies, where five articles reported prospective longitudinal results. In cross-sectional studies' analyses, the pooled weighted mean difference for total brain volume (TBV) and gray matter volume (GMV) in obese/overweight participants was -11.59 (95 % CI: -23.17 to -0.02) and -10.98 (95 % CI: -20.78 to -1.18), respectively. TBV was adversely associated with BMI and WC, GMV with BMI, and hippocampal volume with BMI, WC, and WHR. WC/WHR are associated with a risk of lacunar and white matter hyperintensity (WMH). In longitudinal studies' analyses, BMI was not statistically associated with the overall structural brain abnormalities (for continuous BMI: RR = 1.02, 95 % CI: 0.94-1.12; for categorial BMI: RR = 1.18, 95 % CI: 0.75-1.85). Small sample size of prospective longitudinal studies limited the power of its pooled estimates. A higher BMI is associated with lower brain volume while greater WC/WHR, but not BMI, is related to a risk of lacunar infarct and WMH. Future longitudinal research is needed to further elucidate the specific causal relationships and explore preventive measures.

Relationship between Central Obesity and the incidence of Cognitive Impairment and Dementia from Cohort Studies Involving 5,060,687 Participants.

Central obesity, measured by the waist circumference (WC) or waist-to-hip ratio, has been linked with metabolic dysfunction and structural abnormalities in the brain, two risk factors for cognitive impairment and dementia. The current analysis was performed to understand the influence of central obesity on the incidence of cognitive impairment and dementia. It included 21 studies involving 5,060,687 participants and showed that a high WC was associated with a greater risk of cognitive impairment and dementia (HR = 1.10, 95 % CI: 1.05-1.15), compared with a low WC. Sub-group analysis showed that a high WC increased the likelihood of developing cognitive impairment and dementia in individuals older than 65 years of age (HR = 1.13, 95 % CI: 1.08-1.19), whereas no association was observed in individuals younger than 65 years of age (HR = 1.04, 95 % CI: 0.93-1.16). Furthermore, dose-response meta-analysis confirmed that a high WC was a risk factor for cognitive impairment and dementia. In conclusion, central obesity, as measured by WC, was associated with a risk of cognitive impairment and dementia.

Impact of antidiabetic agents on dementia risk: A Bayesian network meta-analysis.

BACKGROUND: Dementia is more prevalent among people with type 2 diabetes, but little is known regarding the influence of antidiabetic agents on this association. OBJECTIVE: This study assessed the impact of various antidiabetic agents on the risk of dementia among patients with Type 2 diabetes mellitus. METHODS: Relevant studies were retrieved from the PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases. Nine antidiabetic agents were included in the search. Data were pooled via network meta-analysis and meta-analysis. RESULTS: Nine studies were selected for the network meta-analysis with 530,355 individuals and 17 studies for the meta-analysis with 1,258,879 individuals. The analysis excluded glucagon-like peptide 1 (GLP-1) analogs and sodium-dependent glucose transporter 2 (SGLT-2) inhibitors due to the absence of relevant data. The use of dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, thiazolidinedione, and sulfonylurea was associated with a decreased risk of dementia in comparison to no treatment with antidiabetic agents (hazard ratio [HR] for DPP-4 inhibitors, 0.54; 95% confidence interval [CI], 0.38-0.74, HR for metformin, 0.75; 95% CI, 0.63-0.86; HR for sulfonylurea, 0.85; 95%CI, 0.73-0.98 and HR for thiazolidinedione, 0.70; 95% CI, 0.55-0.89, respectively). However, the node-splitting analysis showed the inconsistency of direct and indirect estimates in sulfonylurea (P = 0.042). DPP-4 inhibitors, metformin, thiazolidinedione, and sulfonylurea exhibited a significant impact on the risk of dementia in diabetics compared with insulin (HR, 0.35; 95%CI, 0.20-0.59, HR, 0.48; 95% CI, 0.30-0.77, HR, 0.45; 95% CI, 0.29-0.73 and HR, 0.55; 95% CI, 0.34-0.88, respectively). DPP-4 inhibitors also exhibited a protective effect on the risk of Alzheimer's dementia compared with the no treatment with antidiabetic agents (HR, 0.48; 95% CI, 0.25-0.92). The meta-analysis demonstrated a protective effect of using metformin and DPP-4 inhibitors on the risk of dementia (HR, 0.86; 95% CI, 0.74-1.00 and HR, 0.65; 95% CI, 0.55-0.76, respectively). Further analysis showed insulin was associated with an increased risk of Alzheimer's dementia (HR, 1.60; 95% CI, 1.13-2.26). Only two case-control studies mentioned GLP-1 analogs and SGLT-2 inhibitors, and the pooled ORs showed no evidence of an association with dementia (GLP-1 analogs: 0.71; 95% CI, 0.46-1.10 and SGLT-2 inhibitors: 0.74; 95% CI, 0.47-1.15). CONCLUSION: This analysis indicated that patients with type 2 diabetes under treatment with DPP-4 inhibitors presented with the lowest risk of dementia, followed by those treated with metformin and thiazolidinedione, while treatment with insulin was associated with the highest risk. For the increasing focus on the protective effect on dementia, further specific clinical studies are needed to evaluate the impact of GLP-1 analogs and SGLT-2 inhibitors on the risk of dementia.