Boosting with variant-matched or historical mRNA vaccines protects against Omicron infection in mice.

The large number of spike substitutions in Omicron lineage variants (BA.1, BA.1.1., and BA.2) could jeopardize the efficacy of SARS-CoV-2 vaccines. We evaluated in mice the protective efficacy of the Moderna mRNA-1273 vaccine against BA.1 before or after boosting. Whereas two doses of mRNA-1273 vaccine induced high levels of neutralizing antibodies against historical WA1/2020 strains, lower levels against BA.1 were associated with breakthrough infection and inflammation in the lungs. A primary vaccination series with mRNA-1273.529, an Omicron-matched vaccine, potently neutralized BA.1 but inhibited historical or other SARS-CoV-2 variants less effectively. However, boosting with either mRNA-1273 or mRNA-1273.529 vaccines increased neutralizing titers and protection against BA.1 and BA.2 infection. Nonetheless, the neutralizing antibody titers were higher, and lung viral burden and cytokines were slightly lower in mice boosted with mRNA-1273.529 and challenged with BA.1. Thus, boosting with mRNA-1273 or mRNA-1273.529 enhances protection against Omicron infection with limited differences in efficacy measured.

SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness.

A vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to control the coronavirus disease 2019 (COVID-19) global pandemic. Structural studies have led to the development of mutations that stabilize Betacoronavirus spike proteins in the prefusion state, improving their expression and increasing immunogenicity1. This principle has been applied to design mRNA-1273, an mRNA vaccine that encodes a SARS-CoV-2 spike protein that is stabilized in the prefusion conformation. Here we show that mRNA-1273 induces potent neutralizing antibody responses to both wild-type (D614) and D614G mutant2 SARS-CoV-2 as well as CD8+ T cell responses, and protects against SARS-CoV-2 infection in the lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a phase III trial to evaluate its efficacy.

Genome-wide meta-analysis identifies ancestry-specific loci for Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is a devastating neurological disease with complex genetic etiology. Yet most known loci have only identified from the late-onset type AD in populations of European ancestry. METHODS: We performed a two-stage genome-wide association study (GWAS) of AD totaling 6878 Chinese and 63,926 European individuals. RESULTS: In addition to the apolipoprotein E (APOE) locus, our GWAS of two independent Chinese samples uncovered three novel AD susceptibility loci (KIAA2013, SLC52A3, and TCN2) and a novel ancestry-specific variant within EGFR (rs1815157). More replicated variants were observed in the Chinese (31%) than in the European samples (15%). In combining genome-wide associations and functional annotations, EGFR and TCN2 were prioritized as two of the most biologically significant genes. Phenome-wide Mendelian randomization suggests that high mean corpuscular hemoglobin concentration might protect against AD. DISCUSSION: The current study reveals novel AD susceptibility loci, emphasizes the importance of diverse populations in AD genetic research, and advances our understanding of disease etiology. HIGHLIGHTS: Loci KIAA2013, SLC52A3, and TCN2 were associated with Alzheimer's disease (AD) in Chinese populations. rs1815157 within the EGFR locus was associated with AD in Chinese populations. The genetic architecture of AD varied between Chinese and European populations. EGFR and TCN2 were prioritized as two of the most biologically significant genes. High mean corpuscular hemoglobin concentrations might have protective effects against AD.

Identification and validation of autophagy-related genes influenced by paris polyphylla in tongue cancer using network pharmacology.

BACKGROUND: Tongue squamous cell carcinoma (TSCC) represents the most prevalent form of head and neck squamous cell carcinomas, comprising approximately one-third of all oral cancers. Paris polyphylla(PP) exhibit promising anti-tumor properties, yet their underlying mechanisms remain elusive. This study offers novel insights into the molecular mechanisms underlying TSCC treatment with PP and establishes a theoretical basis for their clinical application. METHODS: Employing transcriptomics and network pharmacology methodologies, we identified autophagy-related key genes associated with the effects of PP. These genes were subjected to KEGG and GO enrichment analyses to determine their related functions. In vitro, CAL-27 cells were treated with 10, 30, and 60 µg/ml of PP for 24 h to assess tumor cell proliferation, apoptosis, and autophagy-related markers. KEY FINDINGS: Molecular docking of MAPK3 and PSEN1 with PP revealed stable hydrogen bond interactions, indicating the therapeutic potential of these saponins in TSCC through the autophagy pathway. In vitro experiments demonstrated significant inhibition of proliferative activity in tongue squamous carcinoma CAL-27 cells and promotion of tumor cell apoptosis by PP. Western blot analysis confirmed alterations in the expression of autophagy markers P62, LC3B, and Beclin1 following treatment, suggesting activation of the autophagy pathway. CONCLUSIONS: Our results suggest that PP inhibits tumor cells through the autophagy pathway, in which MAPK3 and PSEN1 play a role as potential functional molecules.

Combining Multiple Photosensitizer Modules into One Supramolecular System for Synergetic Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT), as an emerging cancer treatment, requires the development of highly desirable photosensitizers (PSs) with integrated functional groups to achieve enhanced therapeutic efficacy. Coordination-driven self-assembly (CDSA) would provide an alternative approach for combining multiple PSs synergistically. Here, we demonstrate a simple yet powerful strategy of combining conventional chromophores (tetraphenylethylene, porphyrin, or Zn-porphyrin) with pyridinium salt PSs together through condensation reactions, followed by CDSA to construct a series of novel metallo-supramolecular PSs (S1-S3). The generation of reactive oxygen species (ROS) is dramatically enhanced by the direct combination of two different PSs, and further reinforced in the subsequent ensembles. Among all the ensembles, S2 with two porphyrin cores shows the highest ROS generation efficiency, specific interactions with lysosome, and strong emission for probing cells. Moreover, the cellular and living experiments confirm that S2 has excellent PDT efficacy, biocompatibility, and biosafety. As such, this study will enable the development of more efficient PSs with potential clinical applications.

Application of the Amyloid/Tau/Neurodegeneration Framework in Cognitively Intact Adults: The CABLE Study.

OBJECTIVES: The amyloid/tau/neurodegeneration (AT[N]) framework has conceptualized the Alzheimer's disease (AD) continuum as a continuum of disease with evidence of amyloid-related pathologies independent of clinical manifestation. Based on this framework, it is necessary to reveal the distribution and risk factors of AD continuum in the cognitively intact population among different cohorts and races, including the northern Chinese Han population. METHODS: This study classified cognitively intact Chinese Alzheimer's Biomarker and LifestylE (CABLE) participants through the AT(N) scheme. Gaussian mixture models were used to identify the cutoff values of cerebrospinal fluid biomarkers, which distinguished AD continuum ( A + T-N-, A + T + N-, A + T-N + and A + T + N +) from 1,005 participants (mean age 61 years; 40% female). Multivariable logistic regressions and Cochran-Armitage trend tests were used to test neuropsychological performance and risk factors for AD continuum. RESULTS: Approximately one-third of individuals (33.7%) belonged to the AD continuum. Four potential modifiable risk factors, including hypertension, thyroid diseases, social isolation, and minimal depression symptoms, were identified for the AD continuum (OR ranging 1.68-6.90). A trend toward higher prevalence of the AD continuum was associated with a larger number of risk factors (p for trend <0.0001). The risk of AD continuum increased by approximately twofold for each additional modifiable risk factor (OR 1.9, 95% CI 1.65-2.24, p < 0.0001). INTERPRETATION: This study revealed the distribution and potential risk factors of the AD continuum in a cognitively intact Han population in northern China, which filled the gap in the area about the performance of the AT(N) framework in the Asian population. ANN NEUROL 2022;92:439-450.

Time spent in outdoor light is associated with the risk of dementia: a prospective cohort study of 362094 participants.

BACKGROUND: Data on the association between free-living daytime sunlight exposure and incident dementia are scarce. The objective is to evaluate whether the time spent in outdoor light is related to the dementia risk and to investigate whether the optimal duration varies with clinical parameters. METHODS: Data were from a prospective cohort of 362,094 UK Biobank participants. A questionnaire survey was conducted to investigate how many hours the participants spent outdoors on typical summer and winter days. A restricted cubic spline (RCS) was performed to explore the potential nonlinear relationship between sunlight exposure and the risk of dementia. We used multivariate Cox proportional hazard regression models to estimate the hazard ratios (HRs) for the associations between sunlight exposure and dementia outcomes, with the change points as a reference. RESULTS: After a median follow-up of 9.0 years, 4149 (1.15%) individuals were diagnosed with dementia. RCS showed a J-shaped relationship between time spent in outdoor light and the dementia risk, with the lowest risk at three change points (1.5 h/day on average, 2 h/day in summer, and 1 h/day in winter). Cox hazard regression models showed a marked increase in risk at low exposure (HR=1.287, 95%CI 1.094-1.515) but a relatively slow increase at higher exposure (HR=1.070, 95%CI 1.031-1.10). Results are more pronounced among participants over 60 years old, females, and those with exactly 7 h of sleep every night. CONCLUSIONS: Sunlight exposure had a J-shaped association with dementia risk. Giving detailed guidance on sunlight exposure can effectively prevent dementia.

Dynamic changes of CSF clusterin levels across the Alzheimer's disease continuum.

BACKGROUND: Clusterin is a multifunctional protein, which is associated with the pathogenesis and the development of Alzheimer's disease (AD). Compared with normal controls, inconsistent results have yielded in previous studies for concentration of cerebrospinal fluid (CSF) clusterin in AD patients. We explored CSF clusterin levels in different pathological processes of AD. METHODS: Following the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria, we employed on the levels of CSF Aß42(A), phosphorylated-Tau (T), and total-tau (N). Based on previously published cutoffs and the close correlation between CSF p-tau and t-tau, 276 participants from the publicly available ADNI database with CSF biomarkers were divided into four groups: A-(TN)- (normal Aß42 and normal p-tau and t-tau; n = 50), A+(TN)- (abnormal Aß42 and normal p-tau and t-tau; n = 39), A+(TN) + (abnormal Aß42 and abnormal p-tau or t-tau; n = 147), A-(TN) + (normal Aß42 and abnormal p-tau or t-tau; n = 40). To assess CSF clusterin levels in AD continuum, intergroup differences in four groups were compared. Pairwise comparisons were conducted as appropriate followed by Bonferroni post hoc analyses. To further study the relationships between CSF clusterin levels and AD core pathological biomarkers, we employed multiple linear regression method in subgroups. RESULTS: Compared with the A-(TN)- group, CSF clusterin levels were decreased in A+ (TN)- group (P = 0.002 after Bonferroni correction), but increased in the A+(TN) + group and the A-(TN) + group (both P <  0.001 after Bonferroni correction). Moreover, we found CSF clusterin levels are positively associated with CSF Aß42 (ß = 0.040, P <  0. 001), CSF p-tau (ß = 0.325, P <  0.001) and CSF t-tau (ß = 0.346, P <  0.001). CONCLUSIONS: Our results indicated that there are differences levels of CSF clusterin in different stages of AD pathology. The CSF clusterin level decreased at the early stage are related to abnormal Aß pathology; and the increased levels are associated with tau pathology and neurodegeneration.

Selenoviologen-Appendant Metallacycles with Highly Stable Radical Cations and Long-Lived Charge Separation States for Electrochromism and Photocatalysis.

Two coordinated metallacycles (rhomboid for M1, hexagonal for M2) with selenoviologens (SeV2+ ) pendants were synthesized via coordination-driven hierarchical self-assembly. M1/M2 with rigid and discrete metallacyclic cores showed tunable optoelectronic properties due to strong π-π stacking and push-pull electron structures. Femtosecond transient absorption (fs-TA) revealed that the formation of macrocyclic structure can not only enhance the stability of radical cation, but also improve the efficiency of intramolecular charge transfer and produce a long-lived charge separation state. The electrochromic performances of M1/M2-based devices were exhibited to show decent radical stabilization. By using M1/M2 as the photocatalyst, the improved catalytic efficiency (>80 %) of visible-light-induced cross-dehydrogenative coupling (CDC) reactions was achieved due to the highly stable radical cations and long-lived charge separation states, which were also confirmed by fs-TA.

Hexaphenylbenzene-Based Deep Blue-Emissive Metallacages as Donors for Light-Harvesting Systems.

We herein report the preparation of a series of hexaphenylbenzene (HPB)-based deep blue-emissive metallacages via multicomponent coordination-driven self-assembly. These metallacages feature prismatic structures with HPB derivatives as the faces and tetracarboxylic ligands as the pillars, as evidenced by NMR, mass spectrometry and X-ray diffraction analysis. Light-harvesting systems were further constructed by employing the metallacages as the donor and a naphthalimide derivative (NAP) as the acceptor, owing to their good spectral overlap. The judiciously chosen metallacage serves as the antenna, providing the suitable energy to excite the non-emissive NAP, and thus resulting in bright emission for NAP in the solid state. This study provides a type of HPB-based multicomponent emissive metallacage and explores their applications as energy donors to light up non-emissive fluorophores in the solid state, which will advance the development of emissive metallacages as useful luminescent materials.

Tetraphenylethylene-Based Multicomponent Emissive Metallacages as Solid-State Fluorescent Materials.

The construction of solid-state fluorescent materials with high quantum yield and good processability is of vital importance in the preparation of organic light-emitting devices. Herein, a series of tetraphenylethylene (TPE)-based multicomponent emissive metallacages are prepared by the coordination-driven self-assembly of tetra-(4-pyridylphenyl)ethylene, cis-Pt(PEt3 )2 (OTf)2 and tetracarboxylic ligands. These metallacages exhibit good emission both in solution and in the solid state because the coordination bonds and aggregation restrict the molecular motions of TPE synergistically, which suppresses the non-radiative decay of these metallacages. Impressively, one of the metallacages achieves very high fluorescence quantum yield (ΦF =88.46 %) in the solid state, which is further used as the coatings of a blue LED bulb to achieve white-light emission. The study not only provides a general method to the preparation of TPE-based metallacages but also explores their applications as solid-state fluorescent materials, which will promote the future design and applications of metallacages as useful emissive devices.

Emissive Platinum(II) Cages with Reverse Fluorescence Resonance Energy Transfer for Multiple Sensing.

It is quite challenging to realize fluorescence resonance energy transfer (FRET) between two chromophores with specific positions and directions. Herein, through the self-assembly of two carefully selected fluorescent ligands via metal-coordination interactions, we prepared two tetragonal prismatic platinum(II) cages with a reverse FRET process between their faces and pillars. Bearing different responses to external stimuli, these two emissive ligands are able to tune the FRET process, thus making the cages sensitive to solvents, pressure, and temperature. First, these cages could distinguish structurally similar alcohols such as n-butanol, t-butanol, and i-butanol. Furthermore, they showed decreased emission with bathochromic shifts under high pressure. Finally, they exhibited a remarkable ratiometric response to temperature over a wide range (223-353 K) with high sensitivity. For example, by plotting the ratio of the maximum emission (I600/I480) of metallacage 4b against the temperature, the slope reaches 0.072, which is among the highest values for ratiometric fluorescent thermometers reported so far. This work not only offers a strategy to manipulate the FRET efficiency in emissive supramolecular coordination complexes but also paves the way for the future design and preparation of smart emissive materials with external stimuli responsiveness.

Fluorescent Metallacycle-Cored Amphiphilic Nanoparticles Formed by ß-Cyclodextrin-Based Host-Guest Interactions towards Cancer Theranostics.

Theranostic agents, taking the advantages of both imaging and therapeutic functions, are anticipated to be key components in the development of personalized medicine in which the therapeutic response can be real-time monitored. Herein, three metallacycles with pendent adamantane groups are prepared by coordination-driven self-assembly of PtII ligands with anticancer activities and tetraphenylethylene derivatives with emission. ß-Cyclodextrin, which shows good host-guest interactions with adamantane moieties, was added to form amphiphilic supramolecular nanoparticles with the aim to enhance the aqueous solubilities and bioactivities of these metallacycles. Moreover, when rhodamine-modified ß-cyclodextrin was used as the carrier, the release of the metallacycles from the nanoparticles could be monitored in situ through the fluorescence changes owing to the efficient fluorescence resonance energy transfer from the metallacycles to rhodamine-modified ß-cyclodextrin. In vitro and in vivo studies showed that these nanoparticles not only served as cell imaging contrast agents but also displayed improved anticancer activities, allowing them to serve as potential candidates for cancer theranostics. This study provides a simple and efficient method to prepare theranostic agents by hierarchical supramolecular self-assembly, which will pave the way for image-guided cancer therapy, targeted cancer therapy, and related biomedical fields.

Unexpected high-temperature stability of ß-Zn4Sb3 opens the door to enhanced thermoelectric performance.

ß-Zn4Sb3 has one of the highest ZT reported for binary compounds, but its practical applications have been hindered by a reported poor stability. Here we report the fabrication of nearly dense single-phase ß-Zn4Sb3 and a study of its thermoelectric transport coefficients across a wide temperature range. Around 425 K we find an abrupt decrease of its thermal conductivity. Past this point, Zn atoms can migrate from crystalline sites to interstitial positions; ß-Zn4Sb3 becomes metastable and gradually decomposes into Zn(hcp) and ZnSb. However, above 565 K it recovers its stability; in fact, the damage caused by decomposition can be repaired completely. This is key to its excellent thermoelectric performance at high temperature: the maximum ZT reaches 1.4. Molecular dynamics simulations are used to shed light on the microscopic behavior of the material.

Insights into stabilization of a viral protein cage in templating complex nanoarchitectures: roles of disulfide bonds.

As a typical protein nanostructure, virus-based nanoparticle (VNP) of simian virus 40 (SV40), which is composed of pentamers of the major capsid protein of SV40 (VP1), has been successfully employed in guiding the assembly of different nanoparticles (NPs) into predesigned nanostructures with considerable stability. However, the stabilization mechanism of SV40 VNP remains unclear. Here, the importance of inter-pentamer disulfide bonds between cysteines in the stabilization of quantum dot (QD)-containing VNPs (VNP-QDs) is comprehensively investigated by constructing a series of VP1 mutants of cysteine to serine. Although the presence of a QD core can greatly enhance the assembly and stability of SV40 VNPs, disulfide bonds are vital to stability of VNP-QDs. Cysteine at position 9 (C9) and C104 contribute most of the disulfide bonds and play essential roles in determining the stability of SV40 VNPs as templates to guide assembly of complex nanoarchitectures. These results provide insightful clues to understanding the robustness of SV40 VNPs in organizing suprastructures of inorganic NPs. It is expected that these findings will help guide the future design and construction of protein-based functional nanostructures.

Oxidative Stress Factors Mediate the Association Between Life's Essential 8 and Accelerated Phenotypic Aging: NHANES 2005-2018.

Cardiovascular health (CVH) is a well-known predictor of morbidity and mortality, while phenotypic age (PhenoAge) is a promising biomarker of aging. This study aimed to explore the association between Life's Essential 8 (LE8), a novel CVH measure, and PhenoAge acceleration (PhenoAgeAccel), as well as the potential mediating role of oxidative stress biomarkers in this relationship. A total of 23 896 individuals were included in the National Health and Nutrition Examination Survey database (2005-2018). Life's Essential 8 scores were categorized into low, moderate, and high groups. PhenoAge, measured through clinical laboratory blood chemistries, served as a marker of biological aging. Weighted linear regression analyses were performed to assess the association between LE8 scores and PhenoAgeAceel. In the multivariable linear regression, LE8 scores were significantly and inversely associated with PhenoAgeAccel, showing a decreased risk in the moderate CVH group (ß -2.98; 95% CI -3.29, -2.66) and high CVH group (ß -4.72; 95% CI -5.08, -4.35) compared to the low CVH group. When treated as a continuous variable, each 10-point increase in LE8 scores corresponded to a 1.14-year decrease in PhenoAge (ß -1.14; 95% CI -1.21, -1.06). Among the 8 individual components in LE8, 7 exhibited a significant negative correlation with PhenoAgeAccel, except for blood lipids. Additionally, mediation analysis revealed that oxidative stress biomarkers, including γ-glutamyltransferase, bilirubin, and uric acid, collectively mediated 17.1% of the associations between LE8 scores and PhenoAgeAccel (p < .001). Higher LE8 scores, representing ideal CVH, are significantly related to a deceleration in PhenoAge, and oxidative stress biomarkers may play a mediating role in this relationship.

Identifying modifiable factors and their joint effect on frailty: a large population-based prospective cohort study.

A thorough understanding and identification of potential determinants leading to frailty are imperative for the development of targeted interventions aimed at its prevention or mitigation. We investigated the potential determinants of frailty in a cohort of 469,301 UK Biobank participants. The evaluation of frailty was performed using the Fried index, which encompasses measurements of handgrip strength, gait speed, levels of physical activity, unintentional weight loss, and self-reported exhaustion. EWAS including 276 factors were first conducted. Factors associated with frailty in EWAS were further combined to generate composite scores for different domains, and joint associations with frailty were evaluated in a multivariate logistic model. The potential impact on frailty when eliminating unfavorable profiles of risk domains was evaluated by PAFs. A total of 21,020 (4.4%) participants were considered frailty, 192,183 (41.0%) pre-frailty, and 256,098 (54.6%) robust. The largest EWAS identified 90 modifiable factors for frailty across ten domains, each of which independently increased the risk of frailty. Among these factors, 67 have the potential to negatively impact health, while 23 have been found to have a protective effect. When shifting all unfavorable profiles to intermediate and favorable ones, overall adjusted PAF for potentially modifiable frailty risk factors was 85.9%, which increases to 86.6% if all factors are transformed into favorable tertiles. Health and medical history, psychosocial factors, and physical activity were the most significant contributors, accounting for 11.9%, 10.4%, and 10.1% respectively. This study offers valuable insights for developing population-level strategies aimed at preventing frailty.

Explore the Role of Frailty as a Contributor to the Association Between AT(N) Profiles and Cognition in Alzheimer's Disease.

Background: The relationship between Alzheimer's disease (AD)-related pathology and cognition was not exactly consistent. Objective: To explore whether the association between AD pathology and cognition can be moderated by frailty. Methods: We included 1711 participants from the Alzheimer's Disease Neuroimaging Initiative database. Levels of cerebrospinal fluid amyloid-ß, p-tau, and t-tau were identified for AD-related pathology based on the amyloid-ß/tau/neurodegeneration (AT[N]) framework. Frailty was measured using a modified Frailty Index-11 (mFI-11). Regression and interaction models were utilized to assess the relationship among frailty, AT(N) profiles, and cognition. Moderation models analyzed the correlation between AT(N) profiles and cognition across three frailty levels. All analyses were corrected for age, sex, education, and APOEɛ4 status. Results: In this study, frailty (odds ratio [OR] = 1.71, p < 0.001) and AT(N) profiles (OR = 2.00, p < 0.001) were independently associated with cognitive status. The model fit was improved when frailty was added to the model examining the relationship between AT(N) profiles and cognition (p < 0.001). There was a significant interaction between frailty and AT(N) profiles in relation to cognitive status (OR = 1.12, pinteraction = 0.028). Comparable results were obtained when Mini-Mental State Examination scores were utilized as the measure of cognitive performance. The association between AT(N) profiles and cognition was stronger with the levels of frailty. Conclusions: Frailty may diminish patients' resilience to AD pathology and accelerate cognitive decline resulting from abnormal AD-related pathology. In summary, frailty contributes to elucidating the relationship between AD-related pathology and cognitive impairment.

Clinical laboratory tests and dementia incidence: A prospective cohort study.

BACKGROUND: Dementia is a major public health issue and a heavy economic burden. It is urgently necessary to understand the underlying biological processes and to identify biomarkers predicting risk of dementia in the preclinical stage for prevention and treatment. METHODS: By using the data of the 367,093 white British individuals from UK Biobank, we investigated the relationship between 56 laboratory measures and 5-year dementia incidence using logistic regression. Adjusted odds ratios for dementia incidence with values below or above the 95 % confidence interval (<2.5th or > 97.5th percentile) on each of clinical laboratory tests were computed. RESULTS: We observed that markers of endocrine dysregulation: elevated hemoglobin A1C (AOR = 2.01 [1.35, 2.88]) was associated with increased dementia incidence. Indicators of liver dysfunction: elevated gamma glutamyltransferase (AOR = 2.28 [1.49, 3.32]), and albumin (AOR = 2.01 [1.15, 3.25]), indicators of renal impairment: high urea (AOR = 1.69 [1.15, 2.40]), and cystatin C (AOR = 1.89 [1.30, 2.67]), and some immune markers, like elevated neutrophill count, low lymphocyte count, and indicators of anemia were also observed to be associated with increased dementia incidence. Both low and high concentrations of insulin-like growth factor 1 were found to be risk factors for dementia. LIMITATIONS: This is an observational study. CONCLUSION: Several systemic biomarkers were associated with dementia incidence. These results implicate a contributory role of diverse biological processes to dementia onset, and enrich our understanding of potential dementia prevention strategy.

Identifying modifiable factors associated with neuroimaging markers of brain health.

AIMS: Brain structural alterations begin long before the presentation of brain disorders; therefore, we aimed to systematically investigate a wide range of influencing factors on neuroimaging markers of brain health. METHODS: Utilizing data from 30,651 participants from the UK Biobank, we explored associations between 218 modifiable factors and neuroimaging markers of brain health. We conducted an exposome-wide association study using the least absolute shrinkage and selection operator (LASSO) technique. Restricted cubic splines (RCS) were further employed to estimate potential nonlinear correlations. Weighted standardized scores for neuroimaging markers were computed based on the estimates for individual factors. Finally, stratum-specific analyses were performed to examine differences in factors affecting brain health at different ages. RESULTS: The identified factors related to neuroimaging markers of brain health fell into six domains, including systematic diseases, lifestyle factors, personality traits, social support, anthropometric indicators, and biochemical markers. The explained variance percentage of neuroimaging markers by weighted standardized scores ranged from 0.5% to 7%. Notably, associations between systematic diseases and neuroimaging markers were stronger in older individuals than in younger ones. CONCLUSION: This study identified a series of factors related to neuroimaging markers of brain health. Targeting the identified factors might help in formulating effective strategies for maintaining brain health.