Association of modified dementia risk score with cerebrospinal fluid biomarkers and cognition in adults without dementia.

Introduction: This study aimed to investigate the cognitive profile and prospective cognitive changes in non-demented adults with elevated Modified Dementia Risk Scores (MDRS), while also exploring the potential relationship between these associations and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathology and neuroinflammation. Methods: Within the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database, 994 participants without dementia were assessed on MDRS, CSF biomarkers and cognition. We examined the associations of the MDRS with CSF biomarkers and cognitive scores using linear regressions. Causal mediation analyses were conducted to analyze the associations among MDRS, brain pathologies, and cognition. The Alzheimer's Disease Neuroimaging Initiative (ADNI) study was used to validate the mediation effects and to investigate the longitudinal association between MDRS and cognitive decline. Results: The results revealed that higher MDRS were linked to poorer cognitive performance (Model 1: PFDR < 0.001; Model 2: PFDR < 0.001) and increases in CSF levels of phosphorylated tau (P-tau, Model 1: PFDR < 0.001; Model 2: PFDR < 0.001), total tau (T-tau, Model 1: PFDR < 0.001; Model 2: PFDR < 0.001), P-tau/Aß42 ratio (Model 1: PFDR = 0.023; Model 2: PFDR = 0.028), T-tau/Aß42 ratio (Model 1: PFDR < 0.001; Model 2: PFDR < 0.001) and soluble triggering receptor expressed on myeloid cells 2 (sTrem2, Model 1: PFDR < 0.001; Model 2: PFDR < 0.001) in the CABLE study. The impact of MDRS on cognition was partially mediated by neuroinflammation and tau pathology. These mediation effects were replicated in the ADNI study. Baseline MDRS were significantly associated with future cognitive decline, as indicated by lower scores on the Mini-Mental State Examination (MMSE, Model 1: PFDR = 0.045; Model 2: PFDR < 0.001), ADNI composite memory score (ADNI-MEM, Model 1: PFDR = 0.005; Model 2: PFDR < 0.001), ADNI composite executive function score (ADNI-EF, Model 1: PFDR = 0.045; Model 2: PFDR < 0.001), and higher score on the Alzheimer's Disease Assessment Scale (ADAS13, Model 1: PFDR = 0.045; Model 2: PFDR < 0.001). Discussion: The findings of this study revealed significant associations between MDRS and cognitive decline, suggesting a potential role of tau pathology and neuroinflammation in the link between MDRS and poorer cognitive performance in individuals without dementia. Consequently, the MDRS holds promise as a tool for targeted preventive interventions in individuals at high risk of cognitive impairment.

Study on the detection rate, genetic polymorphism, viral load, persistent infection capacity, and pathogenicity of human papillomavirus type 81.

Human papillomavirus (HPV) type 81 has recently become one of the most common low-risk HPV types; however, literature focusing on it is limited. This study aimed to analyze the reasons for the increased detection rate of HPV81 and investigate its evolving pathogenicity. We analyzed the detection rates and trends of HPV81 in 229 061 exfoliated cervical cell samples collected from 2014 to 2023; collected samples of HPV81 single infections from two different time periods; and analyzed the allele frequencies, positive selection, viral load, persistent infection capacity, and pathogenicity of E6 and E7 genotypes. We found that the detection rate of HPV81 ranked first among the low-risk types in exfoliated cervical cells and exhibited a significantly increasing trend (p < 0.001). The frequency of the E6 prototype allele of HPV81 (n = 317) was significantly increased (p = 0.018) and demonstrated the strongest adaptive capacity. The viral load and persistent infection capacity of the E6 prototype were significantly higher than those of the mutants, thus serving as key drivers for increasing the detection rate of HPV81 and enhancing its pathogenicity. The viral load was positively correlated with persistent infection capacity and pathogenicity. Persistent infection was a crucial factor in the pathogenicity of HPV81. Successful adaptive evolution of HPV81 is accompanied by enhanced pathogenicity.

Associations between cardiometabolic multimorbidity and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in cognitively intact adults: the CABLE study.

BACKGROUND: Cardiometabolic multimorbidity is associated with an increased risk of dementia, but the pathogenic mechanisms linking them remain largely undefined. We aimed to assess the associations of cardiometabolic multimorbidity with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathology to enhance our understanding of the underlying mechanisms linking cardiometabolic multimorbidity and AD. METHODS: This study included 1464 cognitively intact participants from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database. Cardiometabolic diseases (CMD) are a group of interrelated disorders such as hypertension, diabetes, heart diseases (HD), and stroke. Based on the CMD status, participants were categorized as CMD-free, single CMD, or CMD multimorbidity. CMD multimorbidity is defined as the coexistence of two or more CMDs. The associations of cardiometabolic multimorbidity and CSF biomarkers were examined using multivariable linear regression models with demographic characteristics, the APOE ε4 allele, and lifestyle factors as covariates. Subgroup analyses stratified by age, sex, and APOE ε4 status were also performed. RESULTS: A total of 1464 individuals (mean age, 61.80 years; age range, 40-89 years) were included. The markers of phosphorylated tau-related processes (CSF P-tau181: ß = 0.165, P = 0.037) and neuronal injury (CSF T-tau: ß = 0.065, P = 0.033) were significantly increased in subjects with CMD multimorbidity (versus CMD-free), but not in those with single CMD. The association between CMD multimorbidity with CSF T-tau levels remained significant after controlling for Aß42 levels. Additionally, significantly elevated tau-related biomarkers were observed in patients with specific CMD combinations (i.e., hypertension and diabetes, hypertension and HD), especially in long disease courses. CONCLUSIONS: The presence of cardiometabolic multimorbidity was associated with tau phosphorylation and neuronal injury in cognitively normal populations. CMD multimorbidity might be a potential independent target to alleviate tau-related pathologies that can cause cognitive impairment.

Associations between liver function and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in non-demented adults: The CABLE study.

Liver function has been suggested as a possible factor in the progression of Alzheimer's disease (AD) development. However, the association between liver function and cerebrospinal fluid (CSF) levels of AD biomarkers remains unclear. In this study, we analyzed the data from 1687 adults without dementia from the Chinese Alzheimer's Biomarker and LifestylE study to investigate differences in liver function between pathological and clinical AD groups, as defined by the 2018 National Institute on Aging-Alzheimer's Association Research Framework. We also examined the linear relationship between liver function, CSF AD biomarkers, and cognition using linear regression models. Furthermore, mediation analyses were applied to explore the potential mediation effects of AD pathological biomarkers on cognition. Our findings indicated that, with AD pathological and clinical progression, the concentrations of total protein (TP), globulin (GLO), and aspartate aminotransferase/alanine transaminase (ALT) increased, while albumin/globulin (A/G), adenosine deaminase, alpha-L-fucosidase, albumin, prealbumin, ALT, and glutamate dehydrogenase (GLDH) concentrations decreased. Furthermore, we also identified significant relationships between TP (ß = -0.115, pFDR < 0.001), GLO (ß = -0.184, pFDR < 0.001), and A/G (ß = 0.182, pFDR < 0.001) and CSF ß-amyloid1-42 (Aß1-42 ) (and its related CSF AD biomarkers). Moreover, after 10 000 bootstrapped iterations, we identified a potential mechanism by which TP and GLDH may affect cognition by mediating CSF AD biomarkers, with mediation effect sizes ranging from 3.91% to 16.44%. Overall, our results suggested that abnormal liver function might be involved in the clinical and pathological progression of AD. Amyloid and tau pathologies also might partially mediate the relationship between liver function and cognition. Future research is needed to fully understand the underlying mechanisms and causality to develop an approach to AD prevention and treatment approach.

Association of thyroid disease with risks of dementia and cognitive impairment: A meta-analysis and systematic review.

Introduction: It is still uncertain whether the risk of dementia and cognitive impairment is related to thyroid disease. we carried out a meta-analysis and systematic review (PROSPERO: CRD42021290105) on the associations between thyroid disease and the risks of dementia and cognitive impairment. Methods: We searched PubMed, Embase, and Cochrane Library for studies published up to August 2022. The overall relative risk (RRs) and its 95% confidence interval (CIs) were calculated in the random-effects models. Subgroup analyses and meta-regression were conducted to explore the potential source of heterogeneity among studies. We tested and corrected for publication bias by funnel plot-based methods. The Newcastle-Ottawa Scale (NOS) or Agency for Healthcare Research and Quality (AHRQ) scale were used to evaluate the study quality of longitudinal studies and cross-sectional studies, respectively. Results: A total of 15 studies were included in our meta-analysis. Our meta-analysis showed that hyperthyroidism (RR = 1.14, 95% CI = 1.09-1.19) and subclinical hyperthyroidism (RR = 1.56, 95% CI = 1.26-1.93) might be associated with an elevated risk for dementia, while hypothyroidism (RR = 0.93, 95% CI = 0.80-1.08) and subclinical hypothyroidism (RR = 0.84, 95% CI = 0.70-1.01) did not affect the risk. Discussion: Hyperthyroidism and subclinical hyperthyroidism are predictors of dementia. Systematic review registration: PROSPERO, Identifier: CRD42021290105.

Associations of Lung Function Decline with Risks of Cognitive Impairment and Dementia: A Meta-Analysis and Systematic Review.

BACKGROUND: There are controversies surrounding the effects of lung function decline on cognitive impairment and dementia. OBJECTIVE: We conducted a meta-analysis and systematic review to explore the associations of lung function decline with the risks of cognitive impairment and dementia. METHODS: The PubMed, EMBASE, and the Cochrane Library were searched to identify prospective studies published from database inception through January 10, 2023. We pooled relative risk (RR) and 95% confidence intervals (CI) using random-effects models. The Egger test, funnel plots, meta-regression, sensitivity, and subgroup analyses were conducted to detect publication bias and investigate the source of heterogeneity. RESULTS: Thirty-three articles with a total of 8,816,992 participants were subjected to meta-analysis. Poorer pulmonary function was associated with an increased risk of dementia (FEV: RR = 1.25 [95% CI, 1.17-1.33]; FVC: RR = 1.40 [95% CI, 1.16-1.69]; PEF: RR = 1.84 [95% CI, 1.37-2.46]). The results of the subgroup analyses were similar to the primary results. Individuals with lung diseases had a higher combined risk of dementia and cognitive impairment (RR = 1.39 [95% CI, 1.20-1.61]). Lung disease conferred an elevated risk of cognitive impairment (RR = 1.37 [95% CI, 1.14-1.65]). The relationship between lung disease and an increased risk of dementia was only shown in total study participants (RR = 1.32 [95% CI, 1.11-1.57]), but not in the participants with Alzheimer's disease (RR = 1.39 [95% CI, 1.00-1.93]) or vascular dementia (RR = 2.11 [95% CI, 0.57-7.83]). CONCLUSION: Lung function decline was significantly associated with higher risks of cognitive impairment and dementia. These findings might provide implications for the prevention of cognitive disorders and the promotion of brain health.

Catalytic activation of peroxydisulfate by secondary mineral derived self-modified iron-based composite for florfenicol degradation: Performance and mechanism.

The advanced oxidation processes (AOPs) driven by iron-based materials are the highly efficient technology for refractory organic pollutants treatment. In this work, self-modified iron-based catalysts were prepared using secondary mineral as the precursor by one-step pyrolysis process without additional dopants. The prepared catalysts exhibited excellent performance in catalytic degradation of florfenicol (FF), especially C-AJ, which was derived from ammoniojarosite [(NH4, H3O)Fe3(OH)6(SO4)2], activated PDS to degrade 93% FF with initial concentration of 50 mg/L. Quenching tests and electron paramagnetic resonance (ESR) studies showed that SO4•-, •OH, and •O2- were the main reactive species for FF degradation and their contribution degree was SO4•- > â€¢OH > â€¢O2-. The Fe0 and the cycle of Fe(II)/Fe(III) both contributed to the PDS activation, and the reduction of Fe(III) to Fe(II) was accelerated by S2- on the catalyst surface. In addition, Fe3O4 on the C-AJ indirectly catalyzes PDS by promoting electron transfer. The effects of catalyst dosage, PDS concentration, pH, inorganic anions, and real aqueous matrices on FF degradation, TOC analysis, and cycling test were investigated. The results showed that iron-based catalysts have superior environmental durability due to their excellent catalytic properties in the real aqueous matrices with common inorganic anions and pH 3-9 and its steady catalytic capacity with multiple cycles. Overall, this study sheds new light on the rational design of self-modified iron-based composite and develops low-cost technology toward remediation of FF-contaminated wastewater.

Conductive property of secondary minerals triggered Cr(VI) bioreduction by dissimilatory iron reducing bacteria.

Although secondary minerals have great potential for heavy metal removal, their impact on chromium biogeochemistry in subsurface environments associated with dissimilatory iron reducing bacteria (DIRB) remains poorly characterized. Here, we have investigated the mechanisms of biogenic secondary minerals on the rate of Cr(VI) bioreduction with shewanella oneidensis MR-1. Batch results showed that the biogenic secondary minerals, schwertmannite and jarosite, appreciably increased the Cr(VI) bioreduction rate. UV-vis diffuse reflection spectra showed that schwertmannite and jarosite are semiconductive minerals, which can be activated by MR-1, followed by transferred conduction electrons toward Cr(VI). Cyclic voltammetry and Tafel analysis suggested that the resistance of secondary minerals is a dominant factor controlling Cr(VI) bioreduction. In addition, Cr(VI) adsorption on secondary minerals through ligand exchange promoted Cr(VI) bioreduction by decreasing the electron transfer distance between MR-1 and chromate. Fe(III)/Fe(II) cycling in schwertmannite and jarosite also contributed to Cr(VI) bioreduction as reflected by X-ray photoelectron spectroscopy and Fourier transform infrared spectrometer. Complementary characterizations further verified the contributions of Fe(III)/Fe(II) cycling, Cr(VI) adsorption, and conduction band electron transfer to enhanced Cr(VI) bioreduction. This study provides new insights on the understanding of Cr(VI) bioreduction by semiconductor minerals containing sulfate in subsurface environments.

Characteristics of human papillomaviruses distribution in Guizhou Province, China.

BACKGROUND: Human papillomavirus (HPV) is one of the most common sexually transmitted viruses. Data about HPV infection in Guizhou is limited. METHODS: 56,768 cervical samples were collected and genotyped for 15 main high risk and 6 main low risk HPV types. RESULTS: 16.95% (9623/56768) of samples were HPV positive; 90.70% (8728/9623) of HPV positive women were infected by high risk HPV. High risk and high risk mix infection (1458; 70.85%) was the most common mix HPV infection type. The highest HPV detection rate was found in age group 41-45 years old (detection rate = 17.89%) (χ2 = 204.77; P < 0.001); the highest within-group HPV infection rates were found in the ≤20 (25.62%) and ≥ 61 (24.67%) years old age groups, the lowest within-group HPV infection rate was found in the 31-35 years old age group (15.02%). The highest mix infection proportions were found in the ≥61 (36.06%) and ≤ 20 (33.63%) years old age groups (χ2 = 111.21; P < 0.001), the lowest mix infection proportion was found in the 41-45 (17.42%) years old age group. The highest high risk infection proportions were found in the 26-30 (92.98%), ≥61 (92.68%), and 36-40 (92.16%) years old age groups (χ2 = 31.72; P < 0.001), the lowest high risk infection proportion was found in the ≤20 (84.96%) years old age group. HPV infection rates varied with seasons in Guizhou. CONCLUSIONS: Characteristics of HPV distribution in Guizhou were identified. There were significant differences in HPV distribution among age groups, prevention strategies should be adjusted according to the characteristics.

E6 and E7 gene polymorphisms in human papillomavirus Type-6 identified in Southwest China.

BACKGROUND: Human papillomavirus type-6 (HPV6) is the major etiological agent of anogenital warts both men and women. The present study aimed to characterize the genetic diversity among HPV6 in Southwest China, and to investigate the origin of, selective pressure experienced by, and impact of the resultantly identified genetic variants on the HPV6 secondary structure. METHODS: Phylogenetic trees were constructed by Maximum-likelihood and the Kimura 2-parameters methods by Molecular Evolutionary Genetics Analysis version 6.0. The diversity of secondary structure was analyzed by PSIPred software. The selection pressures acting on the E6/E7 genes were estimated by Phylogenetic Analyses by Maximum Likelihood version 4.8 software. RESULTS: HPV6 was the most prevalent low risk HPV type in southwest China. In total, 143 E6 and E7 gene sequences of HPV6 isolated from patients were sequenced and compared to GenBank HPV6 reference sequence X00203. The results of these analyses revealed that both the HPV6 E6 and E7 were highly conserved within the analyzed patient samples, and comprised only 3 types of variant sequence, respectively. Furthermore, the analysis of HPV6 E6 and E7 sequences revealed seven/five single-nucleotide mutations, two/four and five/one of which were non-synonymous and synonymous, respectively. The phylogenetic analyses of the E6 and E7 sequences indicated that they belonged to sub-lineage A1 and sub-lineage B1, whereas the selective pressure analyses showed that only the E7 mutation sites 4R, 34E, and 52F were positive selection. CONCLUSIONS: HPV6 (detection rate = 13.10%) was very prevalent in southwest China, both the HPV6 E6 and E7 sequences were highly conserved within the analyzed patient samples in southwest China, indicating that the low risk HPV6 can adapt to the environment well without much evolution.

Characteristics of HPV prevalence in Sichuan Province, China.

OBJECTIVE: To investigate the distribution of HPV subtypes and analyze variation in infection trends during a 6-year period in Sichuan Province, China. METHODS: A cross-sectional observational study was conducted at a center in Chengdu between January 1, 2009, and December 31, 2014. Patients with at least one type of cervical disease confirmed by histology and cytology were eligible for inclusion. Cervical specimens were tested for the presence of high-risk and low-risk HPV subtypes by reverse membrane hybridization. RESULTS: Among 10 682 participants, 3370 women (31.5%) were infected with HPV. The most frequently detected high-risk genotypes were HPV16 (n=791; 27.1%), HPV58 (n=476; 16.3%), HPV33 (n=273; 9.4%), HPV52 (n=244; 8.4%), and HPV18 (n=201; 6.9%). The most frequently detected low-risk genotype was HPV6 (n=703; 40.8%). The detection rates of HPV33 (from 7.9% to 10.2%) and HPV58 (from 14.0% to 16.7%) increased over the 6-year period, whereas those of HPV16 (from 32.3% to 24.9%) and HPV18 (from 10.0% to 6.2%) decreased. The prevalence of HPV infection was highest among women aged 21-25 years (χ(2)=191.189; P<0.001). CONCLUSION: HPV58 and HPV33 were the most prevalent subtypes in Sichuan. Changes in the prevalences of infection with different HPV subtypes have been identified.