Does ICU admission dysphagia independently contribute to delirium risk in ischemic stroke patients? Results from a cohort study.

BACKGROUND: Delirium is prevalent in ischemic stroke patients, particularly those in the intensive care unit (ICU), and it poses a significant burden on patients and caregivers, leading to increased mortality rates, prolonged hospital stays, and impaired cognitive function. Dysphagia, a common symptom in critically ill patients with ischemic stroke, further complicates their condition. However, the association between dysphagia and delirium in this context remains unclear. The objective of this study was to investigate the correlation between dysphagia and delirium in ICU patients with ischemic stroke. METHODS: A retrospective analysis was conducted on adult patients diagnosed with ischemic stroke at a medical center in Boston. Ischemic stroke cases were identified using the ninth and tenth revisions of the International Classification of Diseases. Dysphagia was defined as a positive bedside swallowing screen performed by medical staff on the day of ICU admission, while delirium was assessed using the ICU Confusion Assessment Method and review of nursing notes. Logistic regression models were used to explore the association between dysphagia and delirium. Causal mediation analysis was employed to identify potential mediating variables. RESULTS: The study comprised 1838 participants, with a median age of approximately 70 years, and 50.5% were female. Among the total study population, the prevalence of delirium was 43.4%, with a higher prevalence observed in the dysphagia group (60.7% vs. 40.8%, p < 0.001) compared to the non-dysphagia group. After adjusting for confounding factors including age, sex, race, dementia, depression, sedative medications, history of falls, visual or hearing deficit, sequential organ failure score, and Glasgow coma score, multifactorial logistic regression analysis demonstrated a significant association between dysphagia and an increased likelihood of delirium (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 1.07-2.05; p = 0.018; E-value = 1.73). Causal mediation analysis revealed that serum albumin levels partially mediated the association between dysphagia and delirium in critically ill patients with ischemic stroke (average causal mediated effect [ACME]: 0.02, 95% CI: 0.01 to 0.03; p < 0.001). CONCLUSION: ICU admission dysphagia may independently contribute to the risk of delirium in patients with ischemic stroke. Early identification and intervention in ischemic stroke patients with dysphagia may help mitigate the risk of delirium and improve patient prognosis.

Influence of systolic blood pressure trajectory on in-hospital mortality in patients with sepsis.

BACKGROUND: Numerous studies have investigated the mean arterial pressure in patients with sepsis, and many meaningful results have been obtained. However, few studies have measured the systolic blood pressure (SBP) multiple times and established trajectory models for patients with sepsis with different SBP trajectories. METHODS: Data from patients with sepsis were extracted from the Medical Information Mart for Intensive Care-III database for inclusion in a retrospective cohort study. Ten SBP values within 10 h after hospitalization were extracted, and the interval between each SBP value was 1 h. The SBP measured ten times after admission was analyzed using latent growth mixture modeling to construct a trajectory model. The outcome was in-hospital mortality. The survival probability of different trajectory groups was investigated using Kaplan-Meier (K-M) analysis, and the relationship between different SBP trajectories and in-hospital mortality risk was investigated using Cox proportional-hazards regression model. RESULTS: This study included 3034 patients with sepsis. The median survival time was 67 years (interquartile range: 56-77 years). Seven different SBP trajectories were identified based on model-fit criteria. The in-hospital mortality rates of the patients in trajectory classes 1-7 were 25.5%, 40.5%, 11.8%, 18.3%, 23.5%, 13.8%, and 10.5%, respectively. The K-M analysis indicated that patients in class 2 had the lowest probability of survival. Univariate and multivariate Cox regression analysis indicated that, with class 1 as a reference, patients in class 2 had the highest in-hospital mortality risk (P < 0.001). Subgroup analysis indicated that a nominal interaction occurred between age group and blood pressure trajectory in the in-hospital mortality (P < 0.05). CONCLUSION: Maintaining a systolic blood pressure of approximately 140 mmHg in patients with sepsis within 10 h of admission was associated with a lower risk of in-hospital mortality. Analyzing data from multiple measurements and identifying different categories of patient populations with sepsis will help identify the risks among these categories.

The changes in metabolomics profile induced by intermittent theta burst stimulation in major depressive disorder: an exploratory study.

BACKGROUND: Recently, there has been an ongoing interest in the mechanism of intermittent theta burst stimulation (iTBS) in major depressive disorder. Studying the metabolite changes induced by iTBS may help to understand the mechanism. METHODS: Eleven participants with major depressive disorder received 10 days iTBS treatment. Magnetic resonance imaging (MRI) was used to target the region of the left dorsolateral prefrontal cortex (DLPFC) in each participant. We analyzed the effects of iTBS on metabolites using high-throughput profiling and assessed its impact on depressive symptoms. These analyses were considered exploratory, and no correction for multiple comparisons was applied. RESULTS: Among the 318 measured metabolites, a significant increase in cystine, asymmetric dimethylarginine (ADMA), 1-methylhistidine, indoleacetic acid (IAA), diethanolamine (DEA), dopa, riboflavin-5'-monophosphate (FMN), and a significant decrease in alphalinolenic acid (ALA), gamma-linolenic acid (GLA), serotonin, linoleic acid (LA) (p < 0.05) were detected in the patients after iTBS treatment. In Pearson correlation analysis, the plasma levels of LA, FMN and ADMA at baseline were significantly related to the reduction rate of the 17-item Hamilton Depression Rating Scale and the Patient Health Questionnaire-9 scores (p < 0.05). CONCLUSIONS: Our study highlights that LA, FMN, ADMA and their relationship with oxidative stress, may be key factors in the antidepressant efficacy of iTBS.

Triglyceride-glucose index as a valuable predictor for aged 65-years and above in critical delirium patients: evidence from a multi-center study.

BACKGROUND: The triglyceride-glucose index (TyG), an established indicator of insulin resistance, is closely correlated with the prognosis of several metabolic disorders. This study aims to investigate the association between the TyG index and the incidence of critical delirium in patients aged 65 years and older. METHODS: We focused on evaluating patients aged 65 years and older diagnosed with critical delirium. Data were obtained from the Medical Information Database for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD). Multivariate logistic regression and restricted cubic spline (RCS) regression were used to determine the relationship between the TyG index and the risk of delirium. RESULTS: Participants aged 65 years and older were identified from the MIMIC-IV (n = 4,649) and eICU-CRD (n = 1,844) databases. Based on optimal thresholds derived from RCS regression, participants were divided into two cohorts: Q1 (< 8.912), Q2 (≥ 8.912). The logistic regression analysis showed a direct correlation between the TyG index and an increased risk of critical delirium among ICU patients aged 65 and older. These findings were validated in the eICU-CRD dataset, and sensitivity analysis further strengthened our conclusions. In addition, the subgroup analysis revealed certain differences. CONCLUSION: This study highlights a clear, independent relationship between the TyG index and the risk of critical delirium in individuals aged 65 years and older, suggesting the importance of the TyG index as a reliable cardio-cerebrovascular metabolic marker for risk assessment and intervention.

Associations of screen-based sedentary activities with all cause dementia, Alzheimer's disease, vascular dementia: a longitudinal study based on 462,524 participants from the UK Biobank.

BACKGROUND: Current drug treatments for dementia aren't effective. Studying gene-environment interactions can help develop personalized early intervention strategies for Alzheimer's disease (AD). However, no studies have examined the relationship between screen-based sedentary activities and genetic susceptibility to AD risk, and further understanding of the causal relationship is also crucial. METHODS: This study included 462,524 participants from the UK Biobank with a follow-up of 13.6 years. Participants' screen-based sedentary activities time was categorized into three groups based on recorded time: ≥ 4 h/day, 2-3 h/day, and ≤ 1 h/day. Cox proportional risk models were used to analyze the association between computer use/TV viewing groups and the risk of all-cause dementia, AD and vascular dementia (VD). Generalized linear model (GLM) were used to examine the relationship between screen-based sedentary activities and brain structure. Bidirectional Mendelian randomization (MR) was used to validate the causal relationship between TV viewing and AD. RESULTS: Compared to TV viewing ≤ 1 h/day, 1)TV viewing 2-3 h/day was correlated with a higher risk of all-cause dementia (HR = 1.09, 95% CI:1.01-1.18, P < 0.05), and TV viewing ≥ 4 h/day was associated with a higher risk of all-cause dementia (HR = 1.29, 95% CI: 1.19-1.40, P < 0.001), AD (HR = 1.25, 95% CI:1.1-1.42, P < 0.001), and VD (HR = 1.24, 95% CI: 1.04-1.49, P < 0.05); 2) TV viewing ≥ 4 h/day was correlated with a higher AD risk at intermediate (HR = 1.34, 95% CI: 1.03-1.75, P < 0.001) and high AD genetic risk score (AD-GRS) (HR = 2.18, 95% CI: 1.65-2.87, P < 0.001);3) TV viewing 2-3 h/day [ß = (-94.8), 95% CI: (-37.9) -(-151.7), P < 0.01] and TV viewing ≥ 4 h/day [ß = (-92.94), 95% CI: (-17.42) -(-168.46), P < 0.05] were correlated with a less hippocampus volume. In addition, a causal effect of TV viewing times was observed on AD analyzed using MR Egger (OR = 5.618, 95%CI:1.502-21.013, P < 0.05). CONCLUSIONS: There was a causal effect between TV viewing time and AD analyzed using bidirectional MR, and more TV viewing time exposure was correlated with a higher AD risk. Therefore, it is recommended that people with intermediate and high AD-GRS should control their TV viewing time to be less than 4 h/ day or even less than 1 h/day.

Can admission Braden skin score predict delirium in older adults in the intensive care unit? Results from a multicenter study.

AIMS AND OBJECTIVES: To investigate whether a low Braden Skin Score (BSS), reflecting an increased risk of pressure injury, could predict the risk of delirium in older patients in the intensive care unit (ICU). BACKGROUND: Delirium, a common acute encephalopathy syndrome in older ICU patients, is associated with prolonged hospital stay, long-term cognitive impairment and increased mortality. However, few studies have explored the relationship between BSS and delirium. DESIGN: Multicenter cohort study. METHODS: The study included 24,123 older adults from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and 1090 older adults from the eICU Collaborative Research Database (eICU-CRD), all of whom had a record of BSS on admission to the ICU. We used structured query language to extract relevant data from the electronic health records. Delirium, the primary outcome, was primarily diagnosed by the Confusion Assessment Method for the ICU or the Intensive Care Delirium Screening Checklist. Logistic regression models were used to validate the association between BSS and outcome. A STROBE checklist was the reporting guide for this study. RESULTS: The median age within the MIMIC-IV and eICU-CRD databases was approximately 77 and 75 years, respectively, with 11,195 (46.4%) and 524 (48.1%) being female. The median BSS at enrollment in both databases was 15 (interquartile range: 13, 17). Multivariate logistic regression showed a negative association between BSS on ICU admission and the prevalence of delirium. Similar patterns were found in the eICU-CRD database. CONCLUSIONS: This study found a significant negative relationship between ICU admission BSS and the prevalence of delirium in older patients. RELEVANCE TO CLINICAL PRACTICE: The BSS, which is simple and accessible, may reflect the health and frailty of older patients. It is recommended that BSS assessment be included as an essential component of delirium management strategies for older patients in the ICU. NO PATIENT OR PUBLIC CONTRIBUTION: This is a retrospective cohort study, and no patients or the public were involved in the design and conduct of the study.

Body mass index, genetic susceptibility, and Alzheimer's disease: a longitudinal study based on 475,813 participants from the UK Biobank.

BACKGROUND: The association between body mass index (BMI) and Alzheimer's disease (AD) remains controversial. Genetic and environmental factors are now considered contributors to AD risk. However, little is known about the potential interaction between genetic risk and BMI on AD risk. OBJECTIVE: To study the causal relationship between BMI and AD, and the potential interaction between AD genetic risk and BMI on AD risk. METHODS AND RESULTS: Using the UK Biobank database, 475,813 participants were selected for an average follow-up time of more than 10 years. MAIN FINDINGS: 1) there was a nonlinear relationship between BMI and AD risk in participants aged 60 years or older (p for non-linear < 0.001), but not in participants aged 37-59 years (p for non-linear = 0.717) using restricted cubic splines; 2) for participants aged 60 years and older, compared with the BMI (23-30 kg/m2) group, the BMI (< 23 kg/m2) group was associated with a higher AD risk (HR = 1.585; 95% CI 1.304-1.928, p < 0.001) and the BMI (> 30 kg/m2) group was associated with a lower AD risk (HR = 0.741; 95% CI 0.618-0.888, p < 0.01) analyzed using the Cox proportional risk model; 3) participants with a combination of high AD genetic risk score (AD-GRS) and BMI (< 23 kg/m2) were associated with the highest AD risk (HR = 3.034; 95% CI 2.057-4.477, p < 0.001). In addition, compared with the BMI (< 23 kg/m2), the higher BMI was associated with a lower risk of AD in participants with the same intermediate or high AD-GRS; 4) there was a reverse causality between BMI and AD when analyzed using bidirectional Mendelian randomization (MR). CONCLUSION: There was a reverse causality between BMI and AD analyzed using MR. For participants aged 60 years and older, the higher BMI was associated with a lower risk of AD in participants with the same intermediate or high AD genetic risk. BMI (23-30 kg/m2) may be a potential intervention for AD.

Sleep duration, genetic susceptibility, and Alzheimer's disease: a longitudinal UK Biobank-based study.

BACKGROUND: Alzheimer's disease (AD) is the most frequently occurring type of dementia. Concurrently, inadequate sleep has been recognized as a public health epidemic. Notably, genetic and environmental factors are now considered contributors to AD progression. OBJECTIVE: To assess the association between sleep duration, genetic susceptibility, and AD. METHODS AND RESULTS: Based on 483,507 participants from the UK Biobank (UKB) with an average follow-up of 11.3 years, there was a non-linear relationship between AD incidence and sleep duration (P for non-linear < 0.001) by restricted cubic splines (RCS). Sleep duration was categorized into short sleep duration (< 6 h/night), normal sleep duration (6-9 h/night), and long sleep duration (> 9 h/night). No statistically significant interaction was identified between sleep duration and the AD-GRS (Alzheimer's disease genetic risk score, P for interaction = 0.45) using Cox proportional risk model. Compared with the participants who had a low AD-GRS and normal sleep duration, there was associated with a higher risk of AD in participants with a low AD-GRS and long sleep duration (HR = 3.4806; 95% CI 2.0011-6.054, p < 0.001), participants with an intermediate AD-GRS and long sleep duration (HR = 2.0485; 95% CI 1.3491-3.1105, p < 0.001), participants with a high AD-GRS and normal sleep duration (HR = 1.9272; 95% CI 1.5361-2.4176, p < 0.001), and participants with a high AD-GRS and long sleep duration (HR = 5.4548; 95% CI 3.1367-9.4863, p < 0.001).In addition, there was no causal association between AD and sleep duration using Two Sample Mendelian randomization (MR). CONCLUSION: In the UKB population, though there was no causal association between AD and sleep duration analyzed using Two Sample MR, long sleep duration (> 9 h/night) was significantly associated with a higher risk of AD, regardless of high, intermediate or low AD-GRS. Prolonged sleep duration may be one of the clinical predictors of a higher risk of AD.

The Hemoglobin-to-Red Cell Distribution Width Ratio to Predict All-Cause Mortality in Patients with Sepsis-Associated Encephalopathy in the MIMIC-IV Database.

Objective: The hemoglobin-to-red cell distribution width ratio (HRR) is associated with the prognosis of sepsis-associated encephalopathy (SAE). This study aimed to determine the relationship between HRR and SAE and to clarify the possible mechanism of HRR as a prognostic factor for SAE. Methods: A multivariate Cox proportional-hazards regression model was used to assess the correlation between HRR and all-cause mortality. Piecewise linear regression and smooth-curve Cox proportional-hazards regression models were used to observe whether there was a nonlinear relationship between HRR and all-cause mortality in SAE. Results: This study included 8853 patients with SAE. A nonlinear relationship between HRR and SAE was observed through a two-segment regression model. The left inflection point for the HRR threshold was calculated to be 15.54, which was negatively correlated with all-cause mortality (HR = 0.83, 95% CI = 0.76-0.91, p < 0.001). Subgroup analyses revealed significant interactions between white blood cell count, glucose, and patients who received dialysis and HRR. The inverse correlation between HRR and SAE was more pronounced in patients who did not receive vasopressin (HR = 0.91, 95% CI = 0.87-0.96, p < 0.001) than in those who did receive vasopressin (HR = 0.94, 95% CI = 0.88-1.02, p=0.152) and was significantly more pronounced in patients without myocardial infarction (HR = 0.91, 95% CI = 0.88-0.96, p < 0.001) than in those with myocardial infarction (HR = 0.94, 95% CI = 0.87-1.02, p < 0.114). Conclusion: This large retrospective study found a nonlinear relationship between all-cause mortality and HRR in patients with SAE in intensive care units, with low HRR being inversely associated with increased all-cause mortality in patients with SAE.

Antithrombotic Therapy Improves ICU Mortality of Septic Patients with Peripheral Vascular Disease.

Objective: The effectiveness of antithrombotic drugs for treating sepsis is controversial. Here, we explore the association between antithrombotic therapy and intensive care unit (ICU) mortality for septic patients with peripheral vascular disease. Methods: This retrospective cohort study uses data from the Medical Information Mart for Intensive Care (MIMIC)-III database. Kaplan-Meier survival analyses were used to examine mortality among different groups. Cox regression and marginal structural Cox models (MSCMs) were used to adjust for confounding factors. Main Results. The final cohort from the MIMIC-III database included 776 patients, of which 701 survived and 75 perished. The anticoagulant (AC) group and the antiplatelet-anticoagulation (AC-AP) group survived better than the group without antithrombotic treatment (non-AT). The AC and AC-AP groups showed a 0.363-fold and 0.373-fold risk of ICU mortality, respectively, compared with the non-AT group when controlling for age, gender, CRRT, alcohol, heart failure, hypertension, diabetes, obesity, renal failure, liver disease, INR, PT, PPT, and SpO2. Antiplatelet therapy did not reduce ICU mortality. The same trends were apparent from the MSCM. In addition, the AC-AP group exhibited a lower risk of bleeding complications. Conclusion: Although the antithrombotic group (AC and AC-AP groups) demonstrated a higher sequential organ failure assessment (SOFA) score than the group without antithrombotic treatment (non-AT group), the risk of ICU mortality was lower without increasing the risk of bleeding complications. Our study further suggested that anticoagulation therapy may benefit the prognosis of septic patients with peripheral vascular disease.

Clinical study of central cholinergic pathway damage in two mild cognitive impairment patients.

OBJECTIVES: To explore the role of the central cholinergic system in amnestic mild cognitive impairment (aMCI) and mild vascular cognitive impairment (vMCI). METHODS: Twenty-five aMCI patients and 25 vMCI patients were enrolled in this study, and 25 healthy people were chosen as a control group. All participants performed a set of cognitive function scales and were subjected to a brain MRI. We analyzed differences in neuropsychological damage between groups, as well as the degree of brain atrophy and changes in the microstructure of central cholinergic pathways (CCP) in relation to effects on neuropsychological scores. RESULTS: (1) Regarding neuropsychological characteristics of the three groups, scores on the MoCA scale, immediate memory, delayed recall, cued recall, long time prolonged recognition, and CDR-SB of the control group were significantly better than those of the aMCI and vMCI groups. Scores on immediate memory, delayed memory, cued recall, long time delayed recognition, and Forward of Digital Span Test (FDST) in the aMCI group were lower than those in the vMCI group. Compared with the aMCI group, the vMCI group was significantly delayed in Trail Making Test (TMA)-A, TMT-B, and TMT B-A. There were no significant differences in HAMA, HAMD, MMSE, MoCA, the Boston Naming Test (BNT), language fluency or visual scale of posterior atrophy (Koedam score) between the vMCI and aMCI groups. (2) As for microstructure changes in the central cholinergic pathway, vMCI group had a decreased FA value in the cingulum (Cing) of the medial pathway, but an increased MD value in the external capsule (Excap) of the lateral pathway when compared to other two groups. Furthermore, the CingMD value of the vMCI group was higher than that of the control group, but the difference was not obvious when compared to the aMCI group. (3) Last, we researched microstructural changes to CCP, degree of brain atrophy, and neuropsychological scores by using partial correlation analysis for all participants. CingFA was negatively correlated with TMT-B, B-A, and FDST. CingMD was negatively correlated with FDST. ExcapFA was positively correlated with MMSE and Backward of BDST, while ExcapMD was negatively correlated with MMSE and MoCA. Claustrum (Claus)FA was positively related to MoCA and FDST, but was negatively related to TMT-A. ClausMD was negatively correlated with MoCA and language fluency. Koedam score was positively correlated with CDR-SB, ExcapMD, and ClausMD, but negatively correlated with MMSE score and inverse BDST. CONCLUSION: The central cholinergic system is involved in the cognitive impairment of both aMCI and vMCI, and their mechanisms may be distinct. aMCI patients may present with primary CCP impairment while vMCI patients probably exhibit impairment secondary to vasogenic damage to the cholinergic system projection network. The lateral cholinergic pathway was more severely impaired than the medial pathway in vMCI patients, in addition to being associated with decreased executive and general cognitive functions. The damage to CCP was related to the degree of brain atrophy, and both may be involved in the development and progression of cognitive dysfunction.

Research Progress on the Weak Immune Response to the COVID-19 Vaccine in Patients with Type 2 Diabetes.

Coronavirus Disease 2019 (COVID-19) is generally susceptible to the population, highly infectious, rapidly transmitted, and highly fatal. There is a lack of specific drugs against the virus at present and vaccination is the most effective strategy to prevent infection. However, studies have found that some groups, particularly patients with diabetes, show varying degrees of weak immune reactivity to various COVID-19 vaccines, resulting in poor preventive efficacy against the novel coronavirus in patients with diabetes. Therefore, in this study, patients with type 2 diabetes mellitus (T2DM) who had weak immune response to the COVID-19 vaccine in recent years were analyzed. This article reviews the phenomenon, preliminary mechanism, and related factors affecting weak vaccine response in patients with T2DM, which is expected to help in the development of new vaccines for high-risk groups for COVID-19.

Feelings of tense and risk of incident dementia: A prospective study of 482,360 individuals.

BACKGROUND: The relationship between feelings of tense, as a significant emotional distress, and dementia remains unclear. This study aimed to evaluate the association between feelings of tense and dementia. METHODS: In UK Biobank, feelings of tense were measured with a standard item. The primary outcome was all cause of dementia (ACD) and its subtypes (Alzheimer's disease (AD), vascular dementia (VD), and other dementia). Cox regression models analyzed the association between feelings of tense and dementia risk, while linear regression examined the correlation with neuroimaging outcomes. The potential association and joint effects of AD and tenseness were evaluated based on the established genetic risk score (GRS). RESULTS: During a median follow-up of 12.7 years among 482,360 participants, 7331 dementia cases were identified. Individuals with feelings of tense had a significantly increased risk of ACD (HR, 1.194; 95 % CI: 1.115-1.278), VD (HR, 1.164; 95 % CI: 1.007-1.346), and other dementia (HR, 1.181; 95 % CI: 1.081-1.289), but not AD in multi-adjusted models. This association persisted across various sensitivity analyses and exhibited some heterogeneity in subgroup analyses. Furthermore, feelings of tense are associated with total brain volume shrinkage, higher white matter hyperintensities, and decreased partial subcortical volume, particularly in the hippocampus. No interaction between tenseness and AD genetic susceptibility was observed (P for interaction =0.346). LIMITATIONS: Our study only considered feelings of tense measured at a one-time point. CONCLUSIONS: Our findings demonstrate a significant association between feeling of tense and elevated dementia risk, indicating that tenseness could serve as a modifiable psychological determinant for dementia.

Dietary inflammatory index, genetic susceptibility and risk of incident dementia: a prospective cohort study from UK biobank.

BACKGROUND: Genetic factors, diet and inflammation are associated with the development of dementia. In this study, we aimed at evaluating the impact of the dietary inflammatory index (DII) scores and genetic susceptibility on the development of dementia. METHODS: This prospective study involved 207,301 participants aged between 39 and 72 years from UK biobank. A web-based 24-h dietary questionnaire was collected at least once from participants between 2006 and 2012. The DII was calculated based on inflammatory effect score of nutrients. Individual AD-GRS (Alzheimer's disease genetic risk score) was calculated. Incident dementia was ascertained through hospital or death records. RESULTS: Of all 207,301 participants, 468 incident cases of all-cause dementia (165 AD, 91 VD and 26 FTD) were reported during a follow-up period of 11.4 years. The participants in the highest quintile (Q) of DII scores reported a higher risk for all-cause dementia (Q5 vs. Q3, hazard ratio (HR) = 1.702; 95% CI: 1.285-2.255) and VD (Q5 vs. Q3, HR = 2.266, 95% CI: 1.133-4.531) compared to participants in the Q3. Besides, when compared with the Q1, there was a higher risk for AD in the subjects of Q5 (Q5 vs. Q1, HR = 1.590; 95% CI: 1.004-2.519). There was a non-linear relationship between DII score and all-cause incidence (P for non-linear = 0.038) by restricted cubic splines. Subgroup analysis found that the increased risk for all-cause dementia and AD was more pronounced in the elderly, women, and higher educated population. Cox regression models indicated that compared with the participants who had a low AD-GRS risk and in the lowest tertile of DII, participants had a high AD-GRS and the highest tertile of DII were associated with a higher risk of AD (HR = 1.757, 95% CI: 1.082-2.855, P = 0.023). CONCLUSIONS: The DII scores were independently associated with an augmented risk for all-cause dementia, AD and VD. Additionally, high AD-GRS with higher DII scores was significantly associated with a higher risk of AD.

Associations of Folate/Folic Acid Supplementation Alone and in Combination With Other B Vitamins on Dementia Risk and Brain Structure: Evidence From 466 224 UK Biobank Participants.

Previous researchers have tried to explore the association between folate/folic acid intake and dementia incidence, but the results remain controversial. We evaluated the associations of folate/folic acid supplementation alone and in combination with other B vitamins on dementia risk and brain structure. A total of 466 224 UK Biobank participants were investigated. Cox proportional hazards models were used to assess the associations between folate/folic acid supplementation status and the risk of Alzheimer's disease (AD) and vascular dementia (VD). Multivariable linear regression models were employed to evaluate the association between folate/folic acid supplementation status and brain structure. In the final model, folate/folic acid supplementation alone was significantly associated with a higher risk of AD (hazard ratio [HR] = 1.34, 95% confidence interval [CI] = 1.06-1.69, p = .015) and VD (HR = 1.61, 95% CI = 1.21-2.13, p = .001). Folate/folic acid supplementation alone was associated with a reduction in the hippocampus (ß = -95.25 mm3, 95% CI = -165.31 to -25.19 mm3, p = .014) and amygdala (ß = -51.85 mm3, 95% CI = -88.02 to -15.68 mm3, p = .012). The risk of AD and VD, as well as brain structure, in the group with combined folate/folic acid supplementation and other B vitamins did not show a statistically significant difference compared to the reference group (all p > .05). Folate/folic acid supplementation alone is significantly associated with a higher risk of AD and VD, as well as adverse alterations in brain structure. However, when combined with other B vitamins, these detrimental effects can be counteracted.

Associations between the use of common nonsteroidal anti-inflammatory drugs, genetic susceptibility and dementia in participants with chronic pain: A prospective study based on 194,758 participants from the UK Biobank.

OBJECTIVE: To investigate the potential relationship between common nonsteroidal anti-inflammatory drugs (NSAIDs), genetic susceptibility and all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VD) among individuals experiencing chronic pain. METHODS: This study was based on 194,758 chronic pain participants form UK biobank with a median follow-up of 13.7 years. Participants were categorized into different NSAIDs painkiller regimen groups: No NSAIDs group, Aspirin group, Ibuprofen group, Paracetamol group, and 2-3 NSAIDs group. Cox proportional risk models were used to examine the correlation between regular NSAIDs usage and the risk of ACD, AD, and VD. In addition, we further performed subgroup analyses and sensitivity analyses. RESULTS: 1) Compared to the No NSAIDs group, the aspirin group (HR = 1.12, 95% CI:1.01-1.24, P < 0.05), the paracetamol group (HR = 1.15, 95% CI:1.05-1.27, P < 0.01), and the 2-3 NSAIDs group (HR = 1.2, 95% CI:1.08-1.33, P < 0.05) showed a higher risk of ACD. Furthermore, the 2-3 NSAIDs group was also associated with a higher risk of VD (HR = 1.39, 95% CI: 1.08-1.33, P < 0.05). 2) At high dementia GRS participants with chronic pain, the paracetamol group (HR = 1.2, 95% CI: 1.03-1.43, P < 0.05) and the NSAIDs group (HR = 1.3, 95% CI: 1.07-1.59, P < 0.05) were associated with a higher risk of ACD compared to the no painkiller group. 3) There was no significant association between ibuprofen use and higher risk of dementia. CONCLUSION: In individuals with chronic pain, the use of aspirin and paracetamol was associated with a higher risk of ACD, whereas the use of ibuprofen was not significantly associated with a higher risk of ACD.

Effects of selective serotonin reuptake inhibitors (SSRIs) on suicide: A network meta-analysis of double-blind randomized trials.

The relationship between the use of selective serotonin reuptake inhibitors (SSRIs) and suicide risk in patients with mental disorders remains controversial. We conducted a network meta-analysis to examine the effects of SSRIs on suicide risk in patients with mental disorders. A comprehensive search was conducted across PubMed, Web of Science, PsycINFO, CENTRAL, Wanfang Database, and China National Knowledge Infrastructure for articles published until December 19, 2023. The main outcomes were suicidal ideation and instances of suicidal behavior. We included 29 double-blind randomized trials in our analysis. The findings suggest that SSRIs primarily offer short-term protection against suicidal ideation. By week 2, paroxetine, fluoxetine, escitalopram, and non-SSRI treatments were linked to a decreased suicide risk compared with a placebo, with the exception of sertraline. This protective effect was diminished by week 8. In contrast, studies on instances of suicidal behavior from weeks 1 to 10 found no significant difference in efficacy between SSRIs, non-SSRIs, and placebo. These results indicate that SSRIs may offer short-term protection against suicidal ideation. However, their long-term effectiveness in mitigating suicidal ideation and preventing suicidal behaviors is limited.

Association of birthweight and risk of incident dementia: a prospective cohort study.

Given the epidemiological studies investigating the relationship between birthweight and dementia are limited. Our study aimed to explore the association between birthweight and the risk of dementia, cognitive function, and brain structure. We included 275,648 participants from the UK Biobank, categorizing birthweight into quartiles (Q1 ≤ 2.95 kg; Q2 > 2.95 kg, ≤ 3.32 kg; Q3 > 3.32 kg, ≤ 3.66 kg; Q4 > 3.66 kg), with Q3 as the reference. Cox regression models and restricted cubic splines estimated the relationship between birthweight and the risk of all causes of dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VD). Multivariable linear regression models assessed the relationship between birthweight, cognitive function, and MRI biomarkers. Over a median follow-up of 13.0 years, 3103 incident dementia cases were recorded. In the fully adjusted model, compared to Q3 (> 3.32 kg, ≤ 3.66 kg), lower birthweight in Q1 (≤ 2.95 kg) was significantly associated with increased risk of ACD (HR = 1.18, 95%CI 1.06-1.30, P = 0.001) and VD (HR = 1.32, 95%CI 1.07-1.62, P = 0.010), but no significant association with AD was found. Continuous birthweight showed a U-shaped nonlinear association with dementia. Lower birthweight was associated with worse performance in cognitive tasks, including reaction time, fluid intelligence, numeric, and prospective memory. Additionally, certain brain structure indices were identified, including brain atrophy and reductions in area, thickness, and volume of regional subcortical areas. Our study emphasizes the association between lower birthweight and increased dementia risk, correlating cognitive function and MRI biomarkers of brain structure, suggesting that in utero or early-life exposures might impact cognitive health in adulthood.

Radiomics models based on cortical damages for identification of multiple sclerosis with cognitive impairment.

BACKGROUND: Cognitive impairment (CI) is a common symptom in multiple sclerosis (MS) patients. Cortical damages can be closely associated with cognitive network dysfunction and clinically significant CI in MS. So, in this study, We aimed to develop a radiomics model to efficiently identify the MS patients with CI based on clinical data and cortical damages. METHODS: One hundred and eighteen patients with MS were divided into CI and normal cognitive (NC) cohorts (62/56) as defined by the Montreal Cognitive Assessment (MoCA). All participants were randomly divided into train and test sets with a ratio of 7:3. The radiomic features were selected by using the least absolute shrinkage and selection operator (LASSO) method. The discrimination models were built with the support vector machines (SVM) by the clinical data, radiomic features, and merge data, respectively. And the patients were further divided according to each cognitive domain including memory, visuospatial, language, attention and executive, and each domain model was applied by the most suitable classifier. RESULTS: A total of 2298 features were extracted, of which 36 were finally selected. The merge model showed the greatest performance with the area under the curve (AUC) of 0.86 (95 % confidence interval: 0.81-0.91), accuracy (ACC) of 0.78, sensitivity of 0.79 and specificity of 0.77 in test cohort. However, although the visuospatial domain model showed the highest AUC of 0.71 (95 % confidence interval: 0.61-0.81) among five domain models, other domain models did not meet satisfactory results with a relatively low AUC, ACC, sensitivity and specificity. CONCLUSIONS: The radiomics model based on clinical data and cortical damages had a great potential to identify the MS patients with CI for clinical cognitive assessment.

A risk nomogram for predicting prolonged intensive care unit stays in patients with chronic obstructive pulmonary disease.

Background: Providing intensive care is increasingly expensive, and the aim of this study was to construct a risk column line graph (nomograms)for prolonged length of stay (LOS) in the intensive care unit (ICU) for patients with chronic obstructive pulmonary disease (COPD). Methods: This study included 4,940 patients, and the data set was randomly divided into training (n = 3,458) and validation (n = 1,482) sets at a 7:3 ratio. First, least absolute shrinkage and selection operator (LASSO) regression analysis was used to optimize variable selection by running a tenfold k-cyclic coordinate descent. Second, a prediction model was constructed using multifactorial logistic regression analysis. Third, the model was validated using receiver operating characteristic (ROC) curves, Hosmer-Lemeshow tests, calibration plots, and decision-curve analysis (DCA), and was further internally validated. Results: This study selected 11 predictors: sepsis, renal replacement therapy, cerebrovascular disease, respiratory failure, ventilator associated pneumonia, norepinephrine, bronchodilators, invasive mechanical ventilation, electrolytes disorders, Glasgow Coma Scale score and body temperature. The models constructed using these 11 predictors indicated good predictive power, with the areas under the ROC curves being 0.826 (95%CI, 0.809-0.842) and 0.827 (95%CI, 0.802-0.853) in the training and validation sets, respectively. The Hosmer-Lemeshow test indicated a strong agreement between the predicted and observed probabilities in the training (χ2 = 8.21, p = 0.413) and validation (χ2 = 0.64, p = 0.999) sets. In addition, decision-curve analysis suggested that the model had good clinical validity. Conclusion: This study has constructed and validated original and dynamic nomograms for prolonged ICU stay in patients with COPD using 11 easily collected parameters. These nomograms can provide useful guidance to medical and nursing practitioners in ICUs and help reduce the disease and economic burdens on patients.