Cortical thickness reveals sex differences in verbal and visuospatial memory.

Although previous studies have reported the sex differences in behavior/cognition and the brain, the sex difference in the relationship between memory abilities and the underlying neural basis in the aging process remains unclear. In this study, we used a machine learning model to estimate the association between cortical thickness and verbal/visuospatial memory in females and males and then explored the sex difference of these associations based on a community-elderly cohort (n = 1153, age ranged from 50.42 to 86.67 years). We validated that females outperformed males in verbal memory, while males outperformed females in visuospatial memory. The key regions related to verbal memory in females include the medial temporal cortex, orbitofrontal cortex, and some regions around the insula. Further, those regions are more located in limbic, dorsal attention, and default-model networks, and are associated with face recognition and perception. The key regions related to visuospatial memory include the lateral prefrontal cortex, anterior cingulate gyrus, and some occipital regions. They overlapped more with dorsal attention, frontoparietal and visual networks, and were associated with object recognition. These findings imply the memory performance advantage of females and males might be related to the different memory processing tendencies and their associated network.

Age-related enhancement of the association between episodic memory and gray matter volume in medial temporal and frontal lobes.

BACKGROUND: Episodic memory (EM) deteriorates as a result of normal aging as well as Alzheimer's disease. The neural underpinnings of such age-related memory impairments in older individuals are not well-understood. Although previous research has unveiled the association between gray matter volume (GMV) and EM in the elderly population, such findings exhibit variances across distinct age cohorts. Consequently, an investigation into the dynamic evolution of this relationship with advancing age is imperative. RESULT: The present study utilized a sliding window approach to examine how the correlation between EM and GMV varied with age in a cross-sectional sample of 926 Chinese older adults. We found that both verbal EM (VEM) and spatial EM (SEM) exhibited positive correlations with GMV in extensive areas primarily in the temporal and frontal lobes and that these correlations typically became stronger with older age. Moreover, there were variations in the strength of the correlation between EM and GMV with age, which differed based on sex and the specific type of EM. Specifically, the association between VEM and GMVs in the insula and parietal regions became stronger with age for females but not for males, whereas the association between SEM and GMVs in the parietal and occipital regions became stronger for males but not for females. At the brain system level, there is a significant age-related increase in the correlations between both types of EM and the GMV of both the anterior temporal (AT) system and the posterior medial (PM) system in male group. In females, both types of EM show stronger age-related correlations with the GMV of the AT system compared to males. CONCLUSIONS: Our study revealed a significant positive correlation between GMV in most regions associated with EM and age, particularly in the frontal and temporal lobes. This discovery offers new insights into the connection between brain structure and the diminishing episodic memory function among older individuals.

Multi-domain cognition dysfunction accompanies frontoparietal and temporal amyloid accumulation in the elderly.

It is helpful to understand the pathology of Alzheimer's disease by exploring the relationship between amyloid-ß accumulation and cognition. The study explored the relationship between regional amyloid-ß accumulation and multiple cognitions and study their application value in the Alzheimer's disease diagnosis. 135 participants completed 18F-florbetapir Positron Emission Tomography (PET), structural MRI, and a cognitive battery. Partial correlation was used to examine the relationship between global and regional amyloid-ß accumulation and cognitions. Then, a support vector machine was applied to determine whether cognition-related accumulation regions can adequately distinguish the cognitively normal controls (76 participants) and mild cognitive impairment (30 participants) groups or mild cognitive impairment and Alzheimer's disease (29 participants) groups. The result showed that amyloid-ß accumulation regions were mainly located in the frontoparietal cortex, calcarine fissure, and surrounding cortex and temporal pole regions. Episodic memory-related regions included the frontoparietal cortices; executive function-related regions included the frontoparietal, temporal, and occipital cortices; and processing speed-related regions included the frontal and occipital cortices. Support vector machine analysis showed that only episodic memory-related amyloid-ß accumulation regions had better classification performance during the progression of Alzheimer's disease. Assessing regional changes in amyloid, particularly in frontoparietal regions, can aid in the early detection of amyloid-related decline in cognitive function.

Flavihumibacter fluminis sp. nov., a novel thermotolerant bacterium isolated from river silt.

A yellow, Gram-stain-positive, strictly aerobic, thermotolerant, non-motile and rod-shaped bacterial strain, designated RY-1T, was isolated from a silt sample of Fuyang River, Wuqiang County, Hengshui City, Hebei Province, PR China. Cells showed oxidase- and catalase-positive activities. Growth occurred at 20-45 °C (optimum, 37 °C) and pH 6.0-8.0 (optimum, pH 7.0), and in the presence of 0-1.5 % (w/v) NaCl (optimum, 0%). A phylogenetic tree based on 16S rRNA gene sequences revealed that strain RY-1T formed a phylogenetic lineage with Flavihumibacter members within the family Chitinophagaceae. A comparison of 16S rRNA gene sequences showed that strain RY-1T was most closely related to Flavihumibacter cheonanensis WS16T (98.6 %), Flavihumibacter sediminis CJ663T (97.7 %) and Flavihumibacter solisilvae 3-3T (97.6 %). The genome size of strain RY-1T was 4.71 Mb, and the DNA G+C content was 44.3  %. The average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity values between strain RY-1T and reference strains were all lower than the threshold values for species delineation. Strain RY-1T contained menaquinone-7 and iso-C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 1G as the sole respiratory isoprenoid quinone and major cellular fatty acids (≥5 %), respectively. The major polar lipids consisted of phosphatidylethanolamine, three unidentified aminolipids and four unidentified lipids. According to the results of phenotypic, phylogenetic and chemotaxonomic characteristics, strain RY-1T represents a novel species of the genus Flavihumibacter, for which the name Flavihumibacter fluminis sp. nov. is proposed. The type strain is RY-1T (=GDMCC 1.2775T=JCM 34870T).

Isolation and biological activity of natural chalcones based on antibacterial mechanism classification.

Bacterial infection, which is still one of the leading causes of death in humans, poses an enormous threat to the worldwide public health system. Antibiotics are the primary medications used to treat bacterial diseases. Currently, the discovery of antibiotics has reached an impasse, and due to the abuse of antibiotics resulting in bacterial antibiotic resistance, researchers have a critical desire to develop new antibacterial agents in order to combat the deteriorating antibacterial situation. Natural chalcones, the flavonoids consisting of two phenolic rings and a three-carbon α, ß-unsaturated carbonyl system, possess a variety of biological and pharmacological properties, including anti-cancer, anti-inflammatory, antibacterial, and so on. Due to their potent antibacterial properties, natural chalcones possess the potential to become a new treatment for infectious diseases that circumvents existing antibiotic resistance. Currently, the majority of research on natural chalcones focuses on their synthesis, biological and pharmacological activities, etc. A few studies have been conducted on their antibacterial activity and mechanism. Therefore, this review focuses on the antibacterial activity and mechanisms of seventeen natural chalcones. Firstly, seventeen natural chalcones have been classified based on differences in antibacterial mechanisms. Secondly, a summary of the isolation and biological activity of seventeen natural chalcones was provided, with a focus on their antibacterial activity. Thirdly, the antibacterial mechanisms of natural chalcones were summarized, including those that act on bacterial cell membranes, biological macromolecules, biofilms, and quorum sensing systems. This review aims to lay the groundwork for the discovery of novel antibacterial agents based on chalcones.

Brain Network Organization and Aging.

Despite recent substantial progress in neuroscience, the mechanisms and principles of the complex structure, functions, and the relationship between the brain and cognitive functions have not been fully understood. The modeling method of brain network can provide a new perspective for neuroscience research, and it is possible to provide new solutions to the related research problems. On this basis, the researchers define the concept of human brain connectome to highlight and emphasize the importance of network modeling methods in neuroscience. For example, using diffusion-weighted magnetic resonance imaging (dMRI) technology and fiber tractography methods, a white matter connection network of the whole brain can be constructed. From the perspective of brain function, functional magnetic resonance imaging (fMRI) data can build the brain functional connection network. A structural covariation modeling method is used to obtain a brain structure covariation network, and it appears to reflect developmental coordination or synchronized maturation between areas of the brain. In addition, network modeling and analysis methods can also be applied to other types of image data, such as positron emission tomography (PET), electroencephalogram (EEG), and magnetoencephalography (MEG). This chapter mainly reviews the research progress of researchers on brain structure, function, and other aspects at the network level in recent years.

The Aging Patterns of Brain Structure, Function, and Energy Metabolism.

The normal aging process brings changes in brain structure, function, and energy metabolism, which are presumed to contribute to the age-related decline in brain function and cognitive ability. This chapter aims to summarize the aging patterns of brain structure, function, and energy metabolism to distinguish them from the pathological changes associated with neurodegenerative diseases and explore protective factors in aging. We first described the normal atrophy pattern of cortical gray matter with age, which is negatively affected by some neurodegenerative diseases and is protected by a healthy lifestyle, such as physical exercise. Next, we summarized the main types of age-related white matter lesions, including white matter atrophy and hyperintensity. Age-related white matter changes mainly occurred in the frontal lobe, and white matter lesions in posterior regions may be an early sign of Alzheimer's disease. In addition, the relationship between brain activity and various cognitive functions during aging was discussed based on electroencephalography, magnetoencephalogram, and functional magnetic resonance imaging. An age-related reduction in occipital activity is coupled with increased frontal activity, which supports the posterior-anterior shift in aging (PASA) theory. Finally, we discussed the relationship between amyloid-ß deposition and tau accumulation in the brain, as pathological manifestations of neurodegenerative disease and aging.

A new strategy of transforming an ACQ compound into an AIE theranostic system for bacterial imaging and photodynamic antibacterial therapy.

An organic chemical with fluorescence quenching properties [aggregation-caused quenching (ACQ)] may often be transformed by adding functional groups that cause aggregation-induced emission (AIE) to its molecular scaffold. Such structural change techniques, however, sometimes require challenging chemical reactions. SF136 is a type of chalcone, and it is an typical ACQ organic compound. In this study, cationic surfactants like hexadecyltrimethylammonium bromide (CTAB) and polyethyleneimine (PEI) were used to convert the ACQ compound SF136 into an AIE compound without adding any AIE structure units. In comparison to SF136, the SF136-CTAB NPS system not only demonstrated improved bacterial fluorescence imaging capabilities, but also increased photodynamic antibacterial activity, which is connected to its improved targeting and reactive oxygen species (ROS) production abilities. It is a promising theranostic substance against bacteria owing to these enhanced qualities. Other ACQ fluorescent compounds may also benefit from using this approach, broadening the scope of their potential applications.

Flavobacterium selenitireducens sp. nov., isolated from rhizosphere soil of ancient mulberry.

A Gram-stain-negative, non-motile, aerobic, yellow, convex, rod-shaped mesophilic bacterial strain, designated strain D33T, was isolated from rhizosphere soil of ancient mulberry in Dezhou city, Shandong province, PR China. The strain grew at 8-37 °C (optimum, 30 °C), pH 4-9 (optimum, pH 7) and growth occurred at 0.5-5.5 % (w/v) NaCl (optimally at 1 %). The results of the phylogenetic analyses of 16S rRNA gene and whole genome sequences indicated that D33T was closely related to members of the genus Flavobacterium and had the highest 16S rRNA gene sequence similarity with 'Flavobacterium agri' KACC 19300 (95.4 %), Flavobacterium ichthyis NST-5T (94.6 %), Flavobacterium ahnfeltiae KCTC 32467T (93.6 %) and Flavobacterium longum JCM 19141T (93.6 %). The genome size of D33T was 3.8 Mb and the DNA G+C content was 48.0 mol%. The average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH) and average amino acid identity (AAI) values among D33T and reference strains were lower than the threshold values for species delineation. The only respiratory quinone of D33T was menaquinone 6 (MK-6). The predominant fatty acids (>5 %) were C15:0, C16 : 0, C18 : 0, iso-C15:0, iso-C17 : 0 3-OH, anteiso-C15 : 0 and summed feature 9 . The polar lipid profile contained phosphatidylethanolamine, two unidentified aminophospholipids, three unidentified aminolipids and two unidentified lipids. Combined data from phenotypic, phylogenetic and chemotaxonomic studies indicated that D33T is a representative of a novel species of the genus Flavobacterium, for which the name Flavobacterium selenitireducens sp. nov. is proposed. The type strain is D33T (=GDMCC 1.1946T=KACC 22131T).

Sunitinib-based Proteolysis Targeting Chimeras (PROTACs) reduced the protein levels of FLT-3 and c-KIT in leukemia cell lines.

Proteolysis Targeting Chimeras (PROTACs) based on multi-target inhibitors have been reported several times recently. The advantages of PROTACs technology and the synergistic mechanism of multi-target drugs endow this class of protein degraders with special research significance. Herein, twelve new PROTACs based on Sunitinib and VHL-ligand were synthesized and evaluated for their in vitro anticancer activities. Among them, PROTACs 5 (IC50 = 2.9 ± 1.5 µM) exhibited the most significant antiproliferative activity against HL-60 cells. Western blot results showed that PROTAC 5 reduced the protein levels of FLT-3 and c-KIT in HL-60 cells, and induced the degradation of FLT-3 via the ubiquitin-proteasome system. Moreover, PROTACs 5 and 6 reduced the protein levels of FLT-3 in K562 cells. These results suggest that PROTAC 5 has the potential for further research, especially in combination with small molecule kinase inhibitors to study multidrug resistance of tyrosine kinase inhibitors in cancer treatment.

Sex Differences in Cortical Morphometry and White Matter Microstructure During Brain Aging and Their Relationships to Cognition.

Changes in brain structure are associated with aging, and accompanied by the gradual deterioration of cognitive functions, which manifests differently in males and females. Here, we quantify the age-related spatial aging patterns of brain gray and white matter structures, their volume reduction rate, their relationships with specific cognitive functions, as well as differences between males and females in a cross-sectional nondementia dataset. We found that both males and females showed extensive age-related decreases in the volumes of most gray matter and white matter regions. Females have larger regions where the volume decreases with age and a greater slope (females: 0.199%, males: 0.183%) of volume decrease in gray matter. For white matter, no significant sex differences were found in age-related regions, and the slope of volume decrease. More significant associations were identified between brain structures and cognition in males during aging than females. This study explored the age-related regional variations in gray matter and white matter, as well as the sex differences in a nondemented elderly population. This study helps to further understand the aging of the brain structure and sex differences in the aging of brain structures and provides new evidence for the aging of nondemented individuals.

Paraflavitalea devenefica sp. nov., isolated from urban soil.

A Gram-stain-negative, rod-shaped, mesophilic, milky white-pigmented, aerobic, non-spore-forming and non-flagellated bacterium, designated strain X16T, was isolated from urban soil of Zibo, Shandong, China. According to 16S rRNA gene sequence analysis, the isolate showed highest similarities with Paraflavitalea soli 5GH32-13T (97.6 %), Pseudoflavitalea soli KIS20-3T (96.2 %), Pseudobacter ginsenosidimutans Gsoil 221T (96.0 %) and Pseudoflavitalea rhizosphaerae T16R-265T (95.8 %). The neighbour-joining tree based on 16S rRNA gene sequences showed that strain X16T formed a subcluster with Paraflavitalea soli 5GH32-13T, and the subcluster was closely related to Pseudoflavitalea soli KIS20-3T, Pseudobacter ginsenosidimutans Gsoil 221T and Pseudoflavitalea rhizosphaerae T16R-265T. Strain X16T also formed a subcluster with Paraflavitalea soli 5GH32-13T in phylogenetic tree based on genomic sequences. The polar lipids are phosphatidylethanolamine, two unknown aminolipids, two unknown aminophospholipids, two unknown lipids and two unknown phospholipids. The major quinone of strain X16T is menaquinone-7 and the main fatty acids (>10 % of total fatty acids) of strain X16T are iso-C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 1 G. The genome length of strain X16T is 8.7 Mb with a DNA G+C content of 47.4 %. ANI values among strain X16T and strain Paraflavitalea soli 5GH32-13T, Pseudobacter ginsenosidimutans Gsoil 221T, and Pseudoflavitalea rhizosphaerae T16R-265T are 78.1, 70.7, 70.6 %, respectively. On the basis of the results of the polyphasic characterization presented in this study, it is concluded that strain X16T represents a novel species. Besides, strain X16T can detoxify high toxicity selenite [Se(IV)] to low toxicity elemental selenium [Se(0)], for which the name Paraflavitale devenefica sp. nov. is proposed. The type strain is X16T (=KACC 21698T=GDMCC1.1757T).

Roseomonas selenitidurans sp. nov., isolated from urban soil, and emended description of Roseomonas frigidaquae.

An aerobic, non-motile, Gram-stain-negative, pink, convex, coccobacilli-shaped, mesophilic bacterium, designated strain BU-1T, was isolated from an urban soil sample from Zibo city, Shandong province, PR China. The strain grew at 20-37 °C (optimum, 30 °C), pH 5-10 (optimum, pH 7) and growth occurred with 0-2 % (w/v) NaCl (optimally with 0.5 %). The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that BU-1T was closely related to members of the genus Roseomonas and had highest 16S rRNA gene sequence similarities with Roseomonas frigidaquae JCM 15073T (97.8 %), Roseomonas tokyonensis JCM 14634T (96.9 %), Roseomonas stagni JCM 15034T (96.5 %), and Roseomonas riguiloci JCM 17520T (95.9 %). BU-1T also formed a subcluster with R. frigidaquae JCM 15073T and R. stagni JCM 15034T in phylogenetic trees based on genomic sequences. The genome size of BU-1T was 5.79 Mb and the DNA G+C content was 71.7 %. ANI, dDDH and AAI values between BU-1T and R. frigidaquae JCM 15073T were 84.0, 27.2 and 86.7 %, respectively. Furthermore, the genome of BU-1T contained 5446 predicted protein coding genes and 4945 (90.8%) of them had classifiable functions. BU-1T contained Q-10 as the main ubiquinone. The predominant fatty acids (>10 %) were summed feature 3, summed feature 8 and C16:0. The polar lipid profile contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and five unidentified aminolipids. Combined data from phenotypic, phylogenetic and chemotaxonomic studies indicated that strain BU-1T is a representative of a novel species of the genus Roseomonas. Since strain BU-1T can reduce highly toxic selenite [Se(IV)] to low toxicity elemental selenium [Se(0)], the name Roseomonas selenitidurans sp. nov. is proposed. The type strain is BU-1T (=KACC 21750T =GDMCC 1.1776T).

Preparation of a novel monoclonal antibody against caprine interleukin-17A and its applications in immunofluorescence and immunohistochemistry assays.

BACKGROUND: Interleukin-17 (IL-17), the characteristic cytokine secreted by T helper 17 lymphocytes (Th17 cells), plays a pivotal role in host defense and many inflammatory or autoimmune diseases. The aim of this study was to obtain purified protein caprine IL-17A (cIL-17A) as an antigen for preparing an IL-17A-specific monoclonal antibody (mAb). RESULTS: The coding sequence (CDS) region of cIL-17A was cloned from the peripheral blood mononuclear cells (PBMCs) of dairy goats and then inserted into the expression vector PET 32a and transformed into competent TransB (DE3) cells. Recombinant fusion protein obtained under optimized conditions was used to immunize BALB/c mice for preparing monoclonal antibodies. Finally, the supernatants of two hybridoma cell lines showing positive reaction with the recombinant fusion protein and negative reaction with fusion tags of PET 32a were collected for western blot, immunofluorescence (IF) and immunohistochemistry (IHC) analysis. Our results showed that the maximum amount of soluble protein could be obtained directly in the supernatant when the recombinant expression cells were induced by isopropyl-ß-d-thiogalactoside (IPTG) at a concentration of 0.3 mmol/L at 16 °C for 42 h. Western blot analysis showed that the mAb H8 could recognize the eukaryotically expressed cIL-17A in the supernatant of transfected HEK293T cells. Immunofluorescence and immunohistochemistry assays showed that mAb H8 could strongly recognize both the eukaryotically expressed and natural cIL-17A. CONCLUSIONS: The monoclonal antibody mAb H8 prepared in this study may be a potential tool for the detection of cIL-17A and beneficial for investigating the pathogenesis of various IL-17-associated diseases.

Cloning and identification of Bartonella α-enolase as a plasminogen-binding protein.

Bartonella infection is distributed worldwide with animal and public health. Recent studies have shown that host cells infection by Bartonella has a series of different infection stages, beginning with encounter and adherence to the cells. In this study, we expressed and purified recombinant Bartonella henselae (B. henselae) α-enolase. And we found that B. henselae α-enolase is highly conserved in Bartonella species. The interacting protein partners of B. henselae α-enolase were showed by String-11. The interactions between B. henselae α-enolase and human plasminogen were subsequently confirmed by ELISA, pull down, T7 phage display and molecular docking assays. And the plasminogen-binding sites of B. henselae α-enolase are predicted at 247FYKNGSYFY255. These findings will help elucidate and improve the understanding of the molecular mechanisms of Bartonella infection.

Synthesis and biological activities evaluation of sanjuanolide and its analogues.

Sanjuanolide, psorachalcone A and its seven new analogues were synthesized via a combinatorial strategy by aldol reaction. In order to investigate the effect between electron density in π-conjugated systems and biological activities, several electron-withdrawing and electron-donating groups were introduced at C-4 and the phenolic hydroxyl groups of sanjuanolide. The two natural products and its seven new analogues were investigated for their inhibitory effects against five cancer cell lines. Moreover, the hydroxyisoprenyl group may be important to maintain the biological activities of sanjuanolide.

Total synthesis and determination of the absolute configuration of rakicidin A.

Rakicidin A is a cyclic depsipeptide that has exhibited unique growth inhibitory activity against chronic myelogenous leukemia stem cells. Furthermore, rakicidin A has five chiral centers with unknown stereochemical assignment, and thus, can be represented by one of 32 possible stereoisomers. To predict the most probable stereochemistry of rakicidin A, calculations and structural comparison with natural cyclic depsipeptides were applied. A total synthesis of the proposed structure was subsequently completed and highlighted by the creation of a sterically hindered ester bond (C1-C15) through trans-acylation from an easily established isomer (C1-C13). The analytic data of the synthetic target were consistent with that of natural rakicidin A, and then the absolute configuration of rakicidin A was assigned as 2S, 3S, 14S, 15S, 16R. This work suggests strategies for the determination of unknown chiral centers in other cyclic depsipeptides, such as rakicidin B, C, D, BE-43547, and vinylamycin, and facilitates the investigations of rakicidin A as an anticancer stem cell agent.

Effect of the duration of hypertension on white matter structure and its link with cognition.

The relation between hypertension (HTN) and cognition has been reported inclusive results, which may be affected by disease duration. Our study aimed to examine the influence of HTN duration on cognition and its underlying white matter (WM) changes including macrostructural WM hyperintensities (WMH) and microstructural WM integrity. A total of 1218 patients aged ≥55 years with neuropsychological assessment and a subgroup of 233 people with imaging data were recruited and divided into 3 groups (short duration: <5 years, medium duration: 5-20 years, long duration: >20 years). We found that greater HTN duration was preferentially related to worse executive function (EF), processing speed (PS), and more severe WMH, which became more significant during long duration stage. The reductions in WM integrity were evident at the early stage especially in long-range association fibers and then scattered through the whole brain. Increasing WMH and decreasing integrity of specific tracts consistently undermined EF. Furthermore, free water imaging method greatly enhanced the sensitivity in detecting HTN-related WM alterations. These findings supported that the neurological damaging effects of HTN is cumulative and neuroimaging markers of WM at macro- and microstructural level underlie the progressive effect of HTN on cognition.

Polysaccharide- and protein-based hydrogel dressings that enhance wound healing: A review.

Hydrogels can possess desired biochemical and mechanical properties, excellent biocompatibility, satisfactory biodegradability, and biological capabilities that promote skin repair, making them ideal candidates for skin healing dressings. Polysaccharides, such as chitosan, hyaluronic acid and sodium alginate as well as proteins, including gelatin, collagen and fibroin proteins, are biological macromolecules celebrated for their biocompatibility and biodegradability, are at the forefront of innovative hydrogel dressing development. This work first summarizes the skin wound healing process and its influencing factors, and then systematically articulates the multifunctional roles of hydrogels based on biological macromolecules (polysaccharides and proteins) as dressing in addressing bacterial infection, hemorrhage and inflammation during wound healing. Furthermore, this review explores the potential of these hydrogels as vehicles for combination therapy, by incorporating growth factors or stem cells. Finally, the article offers insights into future directions of such hydrogels in wound repair field.

Vascular Risk Factors and Brain Health in Aging: Insights from a Community-Based Cohort Study.

Background: The aging population and high rates of Alzheimer's disease (AD) create significant medical burdens, prompting a need for early prevention. Targeting modifiable risk factors like vascular risk factors (VRFs), closely linked to AD, may provide a promising strategy for intervention. Objective: This study investigates how VRFs influence cognitive performance and brain structures in a community-based cohort. Methods: In this cross-sectional study, 4,667 participants over 50 years old, drawn from the Beijing Ageing Brain Rejuvenation Initiative project, were meticulously examined. Cognitive function and VRFs (diabetes mellitus, hypertension, hyperlipidemia, obesity, and smoking), were comprehensively assessed through one-to-one interviews. Additionally, a subset of participants (n = 719) underwent MRI, encompassing T1-weighted and diffusion-weighted scans, to elucidate gray matter volume and white matter structural network organization. Results: The findings unveil diabetes as a potent detriment to memory, manifesting in atrophy within the right supramarginal gyrus and diminished nodal efficiency and degree centrality in the right inferior parietal lobe. Hypertension solely impaired memory without significant structural changes. Intriguingly, individuals with comorbid diabetes and hypertension exhibited the most pronounced deficits in both brain structure and cognitive performance. Remarkably, hyperlipidemia emerged as a factor associated with enhanced cognition, and preservation of brain structure. Conclusions: This study illuminates the intricate associations between VRFs and the varied patterns of cognitive and brain structural damage. Notably, the synergistic effect of diabetes and hypertension emerges as particularly deleterious. These findings underscore the imperative to tailor interventions for patients with distinct VRF comorbidities, especially when addressing cognitive decline and structural brain changes.