Potential role of blood pressure variability and plasma neurofilament light in the mechanism of comorbidity between Alzheimer's disease and cerebral small vessel disease.

INTRODUCTION: Long-term blood pressure variability (BPV) and plasma neurofilament light (pNfL) have been identified as potential biomarkers for Alzheimer's disease (AD) and cerebral small vessel disease (CSVD). However, the relationship between BPV, pNfL, and their association with the comorbidity of AD and CSVD remains unknown. METHODS: Participants with normal cognition and mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative study were included in the data analysis. Linear mixed-effects regression models and causal mediation analyses were conducted to investigate the relationship among BPV, pNfL, comorbidity-related brain structural changes (hippocampal atrophy and white matter hyperintensities [WMH]), and cognitive function. RESULTS: BPV was associated with pNfL, volumes of hippocampus and WMH, and cognition. pNfL mediated the effects of BPV on brain structural changes and cognition. DISCUSSION: Our findings suggest a potential role of BPV and pNfL in the mechanism of comorbidity between AD and CSVD, underscoring the importance of BPV intervention in the general population. HIGHLIGHTS: Individuals with both Alzheimer's disease (AD) and cerebral small vessel disease (CSVD) pathologies had elevated blood pressure variability (BPV) and plasma neurofilament light (pNfL). The association between different components of BPV and brain structural changes may vary. BPV was associated with pNfL levels independent of average blood pressure. pNfL mediated the effects of BPV on comorbidity-related brain structural changes and cognitive performance.

Associations of tau, Aß, and brain volume of the Papez circuit with cognition in Alzheimer's disease.

This study aimed to investigate the cross-sectional associations between regional Alzheimer's disease (AD) biomarkers, including tau, ß-amyloid (Aß), and brain volume, within the Papez circuit, and neuropsychological functioning across the preclinical and clinical spectrum of AD. We utilized data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, including 251 Aß-positive participants. Participants were categorized into three groups based on the Clinical Dementia Rating (CDR): 73 individuals with preclinical AD (CDR = 0), 114 with prodromal AD (CDR = 0.5), and 64 with clinical AD dementia (CDR ≥ 1). Linear regression analyses, adjusted for age, gender, and education years, were employed to evaluate the associations between five regions of interest (the hippocampus, para-hippocampus, entorhinal cortex, posterior cingulate cortex, and thalamus) and five neuropsychological tests across the three imaging modalities. In the preclinical stage of AD, flortaucipir PET was associated with impaired global cognition and episodic memory (range standardized ß = 0.255-0.498, p < 0.05 corrected for multiple comparisons), while florbetapir PET and brain volume were marginally related to global cognition (range standardized ß = 0.221-0.231, p < 0.05). In the clinical stages of AD (prodromal and dementia), both increased flortaucipir uptake and decreased brain volume were significantly associated with poorer global neuropsychological and episodic memory performance (range standardized ß = 0.222-0.621, p < 0.05, most regions of interest survived correction for multiple comparisions). However, a slight relationship was observed between florbetapir uptake and poorer global cognitive function. The regions most affected by flortaucipir PET were the hippocampus, para-hippocampus, and posterior cingulate cortex. During the clinical stages, the hippocampus and entorhinal cortex exhibited the most significant volumetric changes. Tau PET and brain volume measurements within the Papez circuit are more sensitive indicators of early cognitive deficits in AD than Aß PET. Furthermore, during the clinical stages of AD, both flortaucipir PET and brain volume of the Papez circuit are closely correlated with cognitive decline. These findings underscore the importance of integrating multiple biomarkers for the comprehensive evaluation of AD pathology and its impact on cognition.

Association between serum carotenoids and bacterial vaginosis infection among American women.

BACKGROUND: Bacterial vaginosis (BV) is a widely occurring vaginal inflammation in women of childbearing age caused by dysbiosis of the vaginal flora. Few studies have investigated the effect of serum carotenoids on the development and pathogenesis of BV. This study thus aimed to explore the correlation between serum carotenoids and BV in American women. METHOD: The analysis included 1252 participants with BV from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2004. Multiple logistic regression was conducted to explore the correlation between BV and serum carotenoids, while smooth curve fitting was utilized to examine potential nonlinear correlations. Furthermore, stratified subgroup analyses and sensitivity analyses were conducted. ORs reflected the correlation between BV and serum carotenoids. RESULT: Results of multiple logistic regression indicated that total serum carotenoids and BV had an inverse correlation. In the fully adjusted model II, the quartile with the highest levels of α-carotene and ß-cryptoxanthin had a substantially lower incidence of BV. Smooth curve fitting revealed a significant negative linear correlation between serum carotenoids and the incidence of BV. The negative correlation between serum carotenoids and BV was relatively stable in stratified analyses. Moreover, in sensitivity analyses, the association between serum carotenoids and BV persisted, and ß-carotene became significantly negatively correlated with BV. CONCLUSION: This study found an inverse correlation between serum carotenoids and the prevalence of BV.

The Association of Body Mass Index with Cognition and Alzheimer's Disease Biomarkers in the Elderly with Different Cognitive Status: A Study from the Alzheimer's Disease Neuroimaging Initiative Database.

Background: The association of body mass index (BMI) with cognition and Alzheimer's disease (AD) biomarkers of the elderly remains inconclusive. Objective: To investigate the relationship between BMI and cognition as well as AD biomarkers in the elderly with different cognitive status. Methods: Participants with cognitively normal (CN) were included as the CN group. Participants with mild cognitive impairment and mild dementia were included as the cognitive impairment (CI) group. The relationship between BMI and AD biomarkers (cerebrospinal fluid Aß42 and p-tau181, hippocampal volume [HV]), global cognition (Mini-Mental State Examination [MMSE]), memory, and executive function were explored. Results: In the CI group, BMI was associated with MMSE (ß= 0.03, p = 0.009), Aß42 (ß= 0.006, p = 0.029), p-tau181/Aß42 ratio (ß= -0.001, p = 0.011), and HV (ß= 0.05, p < 0.001). However in the CN group, BMI exhibited associations with p-tau181 (ß= 0.012, p = 0.014) and memory composite score (ß= -0.04, p = 0.038), but not with p-tau181/Aß42 ratio and HV. Moreover, mediation analysis showed that in the CI group, the positive effect of BMI on HV and MMSE score was partially mediated by diastolic blood pressure. Conclusion: The association of BMI with cognition and AD biomarkers varies across different cognitive status. In particular, a lower BMI was associated with worse cognition, higher Aß burden, and lower HV in individuals with CI. Clinical practice should strengthen the monitoring and management of BMI in patients with AD.

Effects of asymptomatic cerebral artery stenosis of anterior circulation and establishment of collateral circulation on cognition.

OBJECTIVE: The purpose of this study is to investigate how cognition is affected by asymptomatic cerebral artery stenosis (CAS) of the anterior circulation and its related collateral circulation. METHODS: 102 patients with CAS of the anterior circulation and 52 controls were enrolled from January 1, 2019 to June 30, 2022. Patients with CAS of anterior circulation were further divided into different subgroups according to the degree of stenosis, cerebral perfusion, and collateral circulation. A series of neuropsychological scales were used to evaluate the participant's cognitive function, activities of daily living, and neuropsychiatric symptoms (such as memory, execution, psychomotor speed, etc.). The data were analyzed using T-test, F-test, chi-square test, rank sum test, and other statistical methods, moreover, the quantitative data were further examined for trends. The relationship between the degree of CAS, cerebral perfusion, collateral circulation, and the outcome of the cognitive test was investigated using Spearman correlation analysis. RESULTS: Compared to controls, there were severe impairments of global cognition, psychomotor speed/execution, memory, attention, activities of daily living, and more neuropsychiatric symptoms in patients with anterior circulation CAS (p < 0.05), and these impairments got worsened with the aggravation of CAS (p < 0.05). The global cognition, psychomotor speed / executive function, memory function, and daily living ability were impaired both in the cerebral perfusion-compensated group and decompensated group(p < 0.05), while there was no statistically significant difference between the two groups (p > 0.05). With the aggravation of CAS, the proportion of poor collateral formation increased, and this difference was statistically significant (P < 0.01). The degree of stenosis, cerebral perfusion, and collateral circulation establishment of anterior circulation CAS was correlated with global cognition, memory, psychomotor speed, execution, attention, activities of daily living, and neuropsychiatric symptoms (all p < 0.01). CONCLUSION: Cognitive impairment and the percentage of inadequate collateral circulation development rise as stenosis progresses in patients with anterior circulation CAS. The decline in global cognitive function was accompanied by impairments in psychomotor speed / executive function, memory function, attention, and daily living skills, as well as the aggravation of neuropsychiatric symptoms, especially in patients with impaired cerebral perfusion and poor collateral circulation formation.

Decreased expression of protein O-linked mannose ß-1,2-N-acetylglucosaminyltransferase 1 contributes to Alzheimer's disease-like pathologies.

Alzheimer's disease (AD) is pathologically characterized by senile plaques and neurofibrillary tangles composed of ß-amyloid peptide (Aß) and tau hyperphosphorylation, respectively. Mannosylation, a particular type of posttranslational modification, may be involved in the pathogenesis of AD. However, its underlying mechanism remains unclear. Protein O-linked mannose ß-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the formation of the N-acetylglucosamine ß-1,2-Man linkage of O-mannosylglycan, which can increase the protein posttranslational mannosylation level. The defective POMGnT1 gene leads to the hypomannosylation of proteins, which may cause cognitive decline in aged people. This study aimed to investigate whether POMGnT1 participated in the pathogenesis of AD and explore its underlying role using AD mouse and cell models. In this study, the expression of POMGnT1 was measured in AD models [ß-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. The results revealed that the expression of POMGnT1 decreased in AD mouse and cell models. In addition, POMGnT1-overexpressing N2a/APP cells were built by retroviral transfection. POMGnT1 overexpression may lower Aß levels by reducing APP production and downregulating ß- and γ-secretase activities. It also promoted clearance of Aß by upregulating insulin-degrading enzymes and ameliorated tau hyperphosphorylation. Hence, it was concluded that POMGnT1 was involved in the pathogenic process of AD. The decreased expression of POMGnT1 contributes to AD-like pathologies.NEW & NOTEWORTHY This study explored the role of mannosylation in the pathogenesis of AD through a mannosyltransferase-POMGnT1. Results demonstrated that target gene overexpression could ameliorate pathologies of Aß and tau hyperphosphorylation. This study is the first to examine the relationship between mannosylation and AD.

Global impacts of future urban expansion on terrestrial vertebrate diversity.

Rapid urban expansion has profound impacts on global biodiversity through habitat conversion, degradation, fragmentation, and species extinction. However, how future urban expansion will affect global biodiversity needs to be better understood. We contribute to filling this knowledge gap by combining spatially explicit projections of urban expansion under shared socioeconomic pathways (SSPs) with datasets on habitat and terrestrial biodiversity (amphibians, mammals, and birds). Overall, future urban expansion will lead to 11-33 million hectares of natural habitat loss by 2100 under the SSP scenarios and will disproportionately cause large natural habitat fragmentation. The urban expansion within the current key biodiversity priority areas is projected to be higher (e.g., 37-44% higher in the WWF's Global 200) than the global average. Moreover, the urban land conversion will reduce local within-site species richness by 34% and species abundance by 52% per 1 km grid cell, and 7-9 species may be lost per 10 km cell. Our study suggests an urgent need to develop a sustainable urban development pathway to balance urban expansion and biodiversity conservation.

Analysis of the expression and distribution of protein O-linked mannose ß1,2-N-acetylglucosaminyltransferase 1 in the normal adult mouse brain.

Introduction: Protein O-linked mannose ß1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) is crucial for the elongation of O-mannosyl glycans. Mutations in POMGNT1 cause muscle-eye-brain (MEB) disease, one of the main features of which is anatomical aberrations in the brain. A growing number of studies have shown that defects in POMGNT1 affect neuronal migration and distribution, disrupt basement membranes, and misalign Cajal-Retzius cells. Several studies have examined the distribution and expression of POMGNT1 in the fetal or neonatal brain for neurodevelopmental studies in the mouse or human brain. However, little is known about the neuroanatomical distribution and expression of POMGNT1 in the normal adult mouse brain. Methods: We analyzed the expression of POMGNT1 mRNA and protein in the brains of various neuroanatomical regions and spinal cords by western blotting and RT-qPCR. We also detected the distribution profile of POMGnT1 in normal adult mouse brains by immunohistochemistry and double-immunofluorescence. Results: In the present study, we found that POMGNT1-positive cells were widely distributed in various regions of the brain, with high levels of expression in the cerebral cortex and hippocampus. In terms of cell type, POMGNT1 was predominantly expressed in neurons and was mainly enriched in glutamatergic neurons; to a lesser extent, it was expressed in glial cells. At the subcellular level, POMGNT1 was mainly co-localized with the Golgi apparatus, but expression in the endoplasmic reticulum and mitochondria could not be excluded. Discussion: The present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective.

Wernicke encephalopathy with extensive cortical lesions combined with diffuse large B-cell lymphoma.

OBJECTIVE: Wernicke encephalopathy (WE) is an acute or subacute neurologic disorder resulting from thiamine deficiency. A Magnetic Resonance Imaging (MRI) test is useful in addition to the clinical manifestation, which is the main basis for the diagnosis. Typical MRI findings include areas surrounding the aqueduct and third ventricle, as well as those in the medial thalamus, dorsal medulla, tectal plate, and mamillary bodies. We reported a case of WE with extensive cortical lesions. The beneficial effects of thiamine supplementation and low dosage of glucocorticoid did not sustain after discharge. Eventually, we found that the condition he had was brought on by gastric diffuse large B-cell lymphoma. Thiamine supplements combined with glucocorticoids may be a good administration regimen. The etiology of WE is frequently disregarded. In individuals with WE, it is essential to take the underlying illness into account. Malignancy, especially gastrointestinal tract cancer, should be considered. A good administration regimen may include glucocorticoids and thiamine supplements.

Interaction between urbanization and the eco-environment in the Pan-Third Pole region.

Due to the high ecological vulnerability of the Pan-Third Pole region and the complexity of its ecological process, the impact of urbanization on the ecological environment (eco-environment) in this specific region attracts global attention. Here, we established an effective framework to evaluate the coupling coordination process of urbanization and eco-environment, and investigated the spatial distribution and dynamic evolution of this coupling coordination. Results showed that the Pan-Third Pole is undergoing an accelerated process of urbanization. Meanwhile, the overall eco-environment has profoundly changed from an ecological reserve to an ecological deficit. The coupling degree between urbanization and eco-environment shows an upward trend, and the decoupling process dynamically changes between various types. Regional convergence is remarkably embodied in the coupling and decoupling types. We found four coupling categories and three decoupling categories for the interaction between urbanization and eco-environment. Among them, the first coupling category contains 35 countries, which maintained a basically coordinated pattern with eco-environment lag. The initial urbanization level of the first category was higher than 35%, indicating that countries with higher urbanization levels were more likely to achieve coordinated development between urbanization and eco-environment. There was a noteworthy "path-dependence" in the evolution of the coordinated relationship between urbanization and eco-environment in the Pan-Third Pole. These findings will have important policy implications for decision-makers to explore coordination and sustainable development path for urbanization and eco-environment conservation.

Primary empty sella: The risk factors and associations with the cerebral small vessel diseases-An observational study.

OBJECTIVE: To investigate the risk factors of primary empty sella (PES) and its associations with cerebral small vessel diseases (CSVD). METHODS: A total of 132 consecutive patients were recruited from Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University from December 2018 to January 2020, including 69 cases of PES, and age, gender-matched 63 subjects without PES. Demographics and clinical characteristics were recorded. Enlarged perivascular spaces (PVS) and white matter hyperintensities (WMH), which are image markers for CSVD, were assessed. Univariate logistic regression models and multivariate logistic regression models were performed to predict the independent risk factors of PES. RESULTS: There was a significant difference in baseline characteristics in terms of hypertension (p < 0.001) and pregnancy (p = 0.019) between PES and the control group; among markers of CSVD, whole WMH (p = 0.030) and periventricular hyperintensities (PVH) (p = 0.027) were significantly different; however, no significant differences concerning deep WMH, total PVS, basilar ganglia-PVS and centrum semiovale-PVS (p > 0.05). After adjusting relevant potential confounders, multivariate logistic regression revealed hypertension (OR=3.158, 95 %CI: 1.452∼6.865, p = 0.004) and pregnancy (OR=2.236, 95 %CI: 1.036-4.826, p = 0.040) were independent risk factors for PES. CONCLUSION: Hypertension and pregnancy are independent risk factors of PES. There is a possible correlation between PES and WMH, especially PVH, however, further studies are required to confirm these findings.