Roles of serum uric acid on the association between arsenic exposure and incident metabolic syndrome in an older Chinese population.

Growing evidences showed that heavy metals exposure may be associated with metabolic diseases. Nevertheless, the mechanism underlying arsenic (As) exposure and metabolic syndrome (MetS) risk has not been fully elucidated. So we aimed to prospectively investigate the role of serum uric acid (SUA) on the association between blood As exposure and incident MetS. A sample of 1045 older participants in a community in China was analyzed. We determined As at baseline and SUA concentration at follow-up in the Yiwu Elderly Cohort. MetS events were defined according to the criteria of the International Diabetes Federation (IDF). Generalized linear model with log-binominal regression model was applied to estimate the association of As with incident MetS. To investigate the role of SUA in the association between As and MetS, a mediation analysis was conducted. In the fully adjusted log-binominal model, per interquartile range increment of As, the risk of MetS increased 1.25-fold. Compared with the lowest quartile of As, the adjusted relative risk (RR) of MetS in the highest quartile was 1.42 (95% confidence interval, CI: 1.03, 2.00). Additionally, blood As was positively associated with SUA, while SUA had significant association with MetS risk. Further mediation analysis demonstrated that the association of As and MetS risk was mediated by SUA, with the proportion of 15.7%. Our study found higher As was remarkably associated with the elevated risk of MetS in the Chinese older adults population. Mediation analysis indicated that SUA might be a mediator in the association between As exposure and MetS.

Association between ambient temperature and risk of notifiable infectious diseases in China from 2011 to 2019.

Previous studies on temperature and infectious diseases primarily focused on individual disease types, yielding inconsistent conclusions. This study collected monthly data on notifiable infectious disease cases and meteorological variables across 7 provinces in China from 2011 to 2019. A distributed lag nonlinear model was used to evaluate the association between ambient temperature and infectious diseases within each province, and random meta-analysis was applied to evaluate the pooled effect. Extreme hot temperature (the 97.5th percentile) was positively associated with the risk of respiratory infectious diseases with the relative risk (RR) of 1.45 (95%CI: 1.01-2.08). Conversely, extreme cold temperature (the 2.5th percentile) was negatively associated with intestinal infectious diseases and zoonotic diseases and vector-borne diseases, reporting RRs of 0.43 (95%CI: 0.30-0.60) and 0.46 (95%CI: 0.38-0.57), respectively. This study described the nonlinear association between ambient temperature and infectious diseases with different transmission routes, informing comprehensive prevention and control strategies for temperature-related infectious diseases.

Cross-sectional study on dysphagia evaluation in community-dwelling older adults using the Eating Assessment Tool (EAT) -10, EAT-2, and Water Swallow Test.

BACKGROUND: Dysphagia is a health concern that causes severe complications and affects the life quality of the older population. This study aimed to determine the diagnostic performance of the Eating Assessment Tool (EAT)-2 compared with the EAT-10 and the Water Swallow Test (WST) in screening for dysphagia. METHODS: A cross-sectional study was conducted among 5,090 community-dwelling older adults. Dysphagia was evaluated using both a subjective measure, the 10-item EAT (EAT-10) and an objective measure, the WST. The kappa index in pairs were analyzed. The validity and reliability of EAT-2 were also assessed. RESULTS: The sensitivity and specificity of the EAT-2 were 96.3 % and 94.8 %, respectively. The kappa index between the EAT-2 and EAT-10 was 0.64, whereas it was 0.11 between the EAT-10 and WST. CONCLUSIONS: The EAT-2 was a simpler screening tool for dysphagia. Combining the subjective questionnaire (EAT-10 or EAT-2) and the objective test (WST) is recommended.

Current evidence, clinical applications, and future directions of transcranial magnetic stimulation as a treatment for ischemic stroke.

Transcranial magnetic stimulation (TMS) is a non-invasive brain neurostimulation technique that can be used as one of the adjunctive treatment techniques for neurological recovery after stroke. Animal studies have shown that TMS treatment of rats with middle cerebral artery occlusion (MCAO) model reduced cerebral infarct volume and improved neurological dysfunction in model rats. In addition, clinical case reports have also shown that TMS treatment has positive neuroprotective effects in stroke patients, improving a variety of post-stroke neurological deficits such as motor function, swallowing, cognitive function, speech function, central post-stroke pain, spasticity, and other post-stroke sequelae. However, even though numerous studies have shown a neuroprotective effect of TMS in stroke patients, its possible neuroprotective mechanism is not clear. Therefore, in this review, we describe the potential mechanisms of TMS to improve neurological function in terms of neurogenesis, angiogenesis, anti-inflammation, antioxidant, and anti-apoptosis, and provide insight into the current clinical application of TMS in multiple neurological dysfunctions in stroke. Finally, some of the current challenges faced by TMS are summarized and some suggestions for its future research directions are made.

Association between health literacy and dysphagia in the community-dwelling older population: a cross-sectional study.

BACKGROUND: Dysphagia, or swallowing disorders, has become a growing concern due to the aging population, and health literacy plays a crucial role in active aging. However, the relationship between them remains unclear. AIMS: To investigate the association between health literacy and dysphagia among community-dwelling older adults in China. METHODS: A survey was conducted on 4462 older adults aged 65 and above in a community in Yiwu City, China, from May 2021 to January 2022. Swallowing problems were assessed using a 30 ml water swallowing test (WST) and the Eating Assessment Tool-10 questionnaire (EAT-10). The participants' health literacy was evaluated using the Chinese Health Literacy Scale (CHLS). Logistic regression and t tests were employed to measure the association between them. RESULTS: The prevalence of dysphagia was 5.70% and 7.85% as determined by EAT-10 and 30 ml-WST, respectively. The health literacy level of community-dwelling older adults was 24.4 ± 4.93 (9-45). Participants with dysphagia exhibited lower levels of health literacy (p < 0.05). The logistic regression model demonstrated an inverse association between health literacy and dysphagia (OR = 0.94, 95%CI = 0.91-0.96 for EAT-10, and OR = 0.93, 95%CI = 0.92-0.95 for WST). Moreover, this association remained significant even after adjusting for covariates. DISCUSSION: Older adults with dysphagia have lower levels of health literacy, particularly in terms of their ability to seek medical advice, acquire and evaluate medical information, and access social support resources. CONCLUSIONS: Health literacy is associated with dysphagia among community-dwelling older adults. Effective interventions should be implemented to provide support in terms of both medical services and social support for this population.

The association between nutritional status and sleep quality of Chinese community-dwelling older adults.

BACKGROUND: Sleep disorders are a common syndrome and could affect the life quality of the older adults. AIMS: This study aimed to investigate the association between nutritional status and sleep quality in the Chinese community-dwelling older adults. METHODS: A total of 2,878 participants ≥ 65 years old from the Yiwu Elderly Cohort were included in the study. Nutritional status was assessed using the Mini Nutritional Assessment Short Form (MNA-SF). Participants were categorized as subjects with malnutrition, at risk of malnutrition or well-nourished based on their MNA-SF score. Pittsburgh Sleep Quality Index (PSQI) was used to identify sleep disorders. PSQI score ≥ 6 was categorized as poor sleep quality. RESULTS: Among the 2,878 participants (mean age 72.71 ± 5.79 years, 50.3% men), 31.5% (n = 906) were classified as having sleep disorders, and 25.5% were identified as malnutrition or at risk of malnutrition. We found a significantly relationship between nutritional status and sleep quality in older adults, and the results showed well-nourished decreased the risk of sleep disorders (OR = 0.32, 95% CI = 0.13, 0.75). And well-nourished status was significantly associated with less daytime dysfunction, adequate sleep duration, and good subjective sleep quality (all P < 0.05). CONCLUSION: There was a close association of nutritional status and sleep quality in older adults. We should pay more attention to the nutritional status of older people with sleep problems, as well as the sleep quality of older adults with malnutrition.

Does physical activity attenuate the association between ambient PM2.5 and physical function?

BACKGROUND: Physical function (PF), such as muscle strength, performing daily activities, has gradually declined with the increase of age, causing the occurrence of disability and diseases burden. Air pollution exposure and physical activity (PA) were both linked to PF. We aimed to explore the individual and joint effects of particulate matter <2.5 µm (PM2.5) and PA on PF. METHODS: A total of 4537 participants and 12,011 observations aged ≥45 years old from the China Health and Retirement Longitudinal Study (CHARLS) cohort from 2011 to 2015 were included into the study. PF was assessed by a combined score of four tests, including grip strength, walking speed, sense of balance, and chair standing tests. Air pollution exposure data was from The ChinaHighAirPollutants (CHAP) dataset. The annual PM2.5 exposure for each individual was estimated based on county-level resident addresses. We estimated the volume of moderate-to-vigorous physical activity (MVPA) by quoting metabolic equivalent (MET). Multivariate linear model was conducted for baseline analysis, and linear mixed model with random participant intercepts was constructed for cohort longitudinal analysis. RESULTS: PM2.5 was negatively associated with PF, while PA was positively associated with PF in baseline analysis. In cohort longitudinal analysis, a 10 µg/m3 increase in PM2.5 was associated to a 0.025 point (95 % CI: -0.047, -0.003) decrease in PF score, and a 10-MET-h/week increase in PA was related to a 0.004 point (95 % CI: 0.001, 0.008) increase in PF score. The association between PM2.5 and PF decreased by increased PA intensity, and PA reversed the detrimental effects between PM2.5 and PF. CONCLUSION: PA attenuated the association of air pollution with PF at both high and low levels of air pollution, implying that PA may be an effective behavior to reduce the adverse effects of poor air quality on PF.

Reprogramming of Activated Pancreatic Stellate Cells via Mechanical Modulation of Transmembrane Force-sensitive N-cadherin Receptor.

Cancer has been the leading cause of death due mainly to tumor metastasis. The tumor microenvironment plays a key role in tumor metastasis. As the main stromal cells in tumor microenvironment originated from activated fibroblast, cancer-associated fibroblasts (CAFs) play a major role in promoting tumor metastasis. A promising therapeutic avenue is reprogramming of CAFs into tumor-restraining quiescence state. In this study, we observed that CAF-like active pancreatic stellate cells (PSCs) interact with each other via N-cadherin, a force-sensitive transmembrane receptor. Since N-cadherin ligation mediated mechanotransduction has been reported to restrict integrin mediated signalling, we thus hypothesized that the reprogramming of activated PSCs by mechanical modulation of N-cadherin ligation might be possible. To test this hypothesis, we grafted N-cadherin ligand (HAVDI peptide) onto soft polyethylene glycol hydrogel substrate prior to cell adhesion to mimic cell-cell interaction via N-cadherin ligation. We found that the activated PSCs could be reprogrammed to their original quiescent state when transferred onto the substrate with immobilized HAVDI peptide. These results reveal a key role of mechanosensing by intercellular transmembrane receptor in reprogramming of activated PSCs, and provide a potential way for designing novel therapeutic strategies for cancer treatment.

Mutant p53 driven-LINC00857, a protein scaffold between FOXM1 and deubiquitinase OTUB1, promotes the metastasis of pancreatic cancer.

Tumour metastasis is the major adverse factor for recurrence and death in pancreatic cancer (PC) patients. P53 mutations are considered to be the second most common type of mutation in PC and significantly promote PC metastasis. However, the molecular mechanisms underlying the effects of p53 mutations, especially the regulatory relationship of the protein with long noncoding RNAs (lncRNAs), remain unclear. In the present study, we demonstrated that the lncRNA LINC00857 exhibits a significantly elevated level in PC and that it is associated with poor prognosis; furthermore, TCGA data showed that LINC00857 expression was significantly upregulated in the mutant p53 group compared with the wild-type p53 group. Gain- and loss-of-function experiments showed that LINC00857 promotes the metastasis of PC cells. We further found that LINC00857 upregulates FOXM1 protein expression and thus accelerates metastasis in vitro and in vivo. Mechanistically, LINC00857 bound simultaneously to FOXM1 and to the deubiquitinase OTUB1, thereby serving as a protein scaffold and enhancing the interaction between FOXM1 and OTUB1, which inhibits FOXM1 degradation through the ubiquitin-proteasome pathway. Interestingly, we found that mutant p53 promotes LINC00857 transcription by binding to its promoter region. Finally, atorvastatin, a commonly prescribe lipid-lowering drug, appeared to inhibit PC metastasis by inhibiting the mutant p53-LINC00857 axis. Taken together, our results provide new insights into the biology driving PC metastasis and indicate that the mutant p53-LINC00857 axis might represent a novel therapeutic target for PC metastasis.

Blood loss during liver transplantation is a predictor of postoperative thrombosis.

Liver transplantation (LT) is an effective way to cure end-stage liver diseases (ESLDs), which have generally been regarded as examples of acquired bleeding disorders. However, postoperative thrombosis after LT is recognised and remains a life-threatening complication. This study aimed to show that blood loss during LT is a predictor of postoperative thrombosis and to establish a predictive model. We analysed the medical records of all patients who underwent LT at the First Affiliated Hospital of Xi'an Jiaotong University from January 2017 to April 2019 to identify the risk factors for post-transplant thrombosis. The predictive nomogram was established based on independent predictors identified by logistic regression analysis. Blood loss during LT of ≥31.25 mL/kg can predict postoperative thrombosis, and the nomogram achieved an accurate prediction.

Huaier suppresses pancreatic cancer progression via activating cell autophagy induced ferroptosis.

Purpose: The anti-tumour effect of Huaier has been demonstrated in a variety of tumours. Ferroptosis is a newly identified type of programmed cell death accompanied by the accumulation of reactive oxygen species (ROS) and iron in cells and plays a key role in the therapeutic process against malignant tumours. We aimed to explore the potential therapeutic role of Huaier in pancreatic cancer and uncover the relationship between Huaier and ferroptosis. Methods: CCK8 and colony formation assays were used to determine the proliferation of pancreatic cancer cells (PCs). The levels of cellular ROS were analysed by a fluorescence probe, and the accumulation of cellular iron was showed by Prussian blue staining. The autophagosomes and mitochondrial morphology were characterised by transmission electron microscopy (TEM). The levels of intracellular glutathione (GSH) and lipid peroxidation were measured by the corresponding kits. Results: The growth inhibitory effect of Huaier on PCs was concentration- and time-dependent, but this effect was significantly attenuated by ferroptosis inhibitors. In addition, Huaier effectively inhibited the GSH-GPX4 antioxidation system and resulted in the massive accumulation of ROS in PCs As shown by TEM, Huaier-treated PCs exhibited a decrease in mitochondrial cristae and a smaller mitochondrion, accompanied by an increase in autophagosomes. Indeed, we found that autophagy can induce ferroptosis in PCs and that Huaier-induced ferroptosis can be suppressed by the autophagosome inhibitor, Wortmannin. Conclusion: Huaier can activate ferroptosis by inducing autophagy in PCs.

Exosome in Crosstalk between Inflammation and Angiogenesis: A Potential Therapeutic Strategy for Stroke.

The endothelial dysfunction, associated with inflammation and vascular permeability, remains the key event in the pathogenesis of cerebral ischemic stroke. Angiogenesis is essential for neuroprotection and neural repair following stroke. The neuroinflammatory reaction plays a vital role in stroke, and inhibition of inflammation contributes to establishing an appropriate external environment for angiogenesis. Exosomes are the heterogeneous population of extracellular vesicles which play critical roles in intercellular communication through transmitting various proteins and nucleic acids to nearby and distant recipient cells by body fluids and circulation. Recent reports have shown that exosomal therapy is a valuable and potential treatment strategy for stroke. In this review, we discussed the exosomes in complex interaction mechanisms of angiogenesis and inflammation following stroke as well as the challenges of exosomal studies such as secretion, uptake, modification, and application.

Mechanically activated ion channel Piezo1 contributes to melanoma malignant progression through AKT/mTOR signaling.

Melanoma is a highly aggressive cancer that can metastasize at early stage. The aim of this study is to clarify the role of Piezo1 and its potential mechanism in regulating the malignant phenotypes of melanoma. In the present study, we first showed that Piezo1 was abnormally expressed in melanoma, which accelerated the malignant progression by activating AKT/mTOR signaling. Firstly, we found that Piezo1 was upregulated in melanoma and associated with poor survival. Additionally, Piezo1 knockdown significantly weakened intracellular calcium signal and viability of melanoma cells. Furthermore, Piezo1 knockdown inhibited the transendothelial migration and invasion in vitro, as well as metastasis in vivo. Mechanistically, we found that Piezo1 activated AKT/mTOR signaling to maintain malignant phenotypes of melanoma. Therefore, Piezo1 acts as an oncogene in melanoma cells and provides a novel candidate for melanoma diagnosis and treatment.

Thiostrepton induces ferroptosis in pancreatic cancer cells through STAT3/GPX4 signalling.

Ferroptosis is a new form of regulated cell death that is mediated by intracellular iron and ester oxygenase, and glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4) prevents ferroptosis by converting lipid hydroperoxides into nontoxic lipid alcohols. Although thiostrepton (TST) has been reported to exert antitumor effects, its role in pancreatic cancer and the underlying mechanisms remain unclear. In this study, we found that TST reduced the viability and clonogenesis of pancreatic cancer cell lines, along with intracellular iron overload, increasing reactive oxygen species (ROS) accumulation, malondialdehyde (MDA) overexpression, and glutathione peroxidase (GSH-PX) depletion. Mechanistically, chromatin immunoprecipitation (ChIP) and dual luciferase reporter gene assays were used to confirm that signal transducer and activator of transcription 3 (STAT3) binds to the GPX4 promoter region and promotes its transcription, whereas TST blocked GPX4 expression by regulating STAT3. Finally, in vivo experiments revealed that TST inhibited the growth of subcutaneously transplanted tumours and had considerable biosafety. In conclusion, our study identified the mechanism by which TST-induced ferroptosis in pancreatic cancer cells through STAT3/GPX4 signalling.

RASAL2 mediated the enhancement of YAP1/TIAM1 signaling promotes malignant phenotypes of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a high incidence of metastasis and dismal prognosis. As a member of Gas-Gap gene, RASAL2 is involved in the hydrolysis of RAS-GTP to RAS-GDP and abnormal expression in human cancers. Here we firstly described the function of RASAL2 on PDAC to enrich the knowledge of RAS family.We interestingly observed that RASAL2 expression was upregulated in PDAC at both mRNA and protein levels, and high expression of RASAL2 predicted a poor prognosis in PDAC patients. Additionally, RASAL2 promoted malignant behaviors of PDAC in vitro and in vivo. To determine the mechanistic roles of RASAL2 signaling and its potential as a therapeutic target in PDAC, we clarified that RASAL2 could accumulate the TIAM1 expression in different level through inhibiting YAP1 phosphorylation, increased TIAM1 mRNA expression and suppressed ubiquitination of TIAM1 protein. In conclusion, RASAL2 enhances YAP1/TIAM1 signaling and promotes PDAC development and progression.

The association of childhood adversities and mental health problems with dual-harm in individuals with serious aggressive behaviors.

BACKGROUND: The coexistence of self-harm and aggression, which is referred to as dual-harm, is commonly seen in forensic population. Self-harm and aggression have often been studied separately, previous studies on risk factors of aggression or self-harm mainly focused on childhood adversities, emotional regulation, impulsivity and psychopathology, given their importance in the two behaviors. However, the factors associated with dual-harm remain unclear. This study aimed to explore potential risk factors associated with co-occurring self-harm among individuals with serious aggressive behaviors. METHODS: This multi-center, cross-sectional case-control study was conducted from May 2013 to January 2016 and involved seven qualified forensic institutes located in seven provinces in China. Participants were individuals with serious aggressive behaviors and were suspected to have mental disorders. Lifetime history of self-harm was obtained by a self-report questionnaire, and serious aggressive behaviors were assessed with the use of participants' forensic archive. Sociodemographic and clinical information were collected using a self-designed standardized data collection form, and childhood adversities was assessed using a clinician-rated scale designed by our research team. The Psychopathy Checklist-Revised (PCL-R) was used to assess psychopathic traits and the Brief Psychiatric Rating Scale (BPRS) was used to assess psychiatric symptoms of the participants. Univariate and multivariate logistic regression analyses were performed to analyze the relevant factors for dual-harm. RESULTS: A total of 423 individuals with serious aggressive behaviors were enrolled in the current study. Of them, 74 (17.5%) with self-harm history assigned into the dual-harm group (D-H) and 349 (82.5%) without self-harm history assigned into the aggression-only group (A-O). According to the binary logistic regression analysis, current diagnosis of mood disorder (OR = 3.2, 95%CI: 1.2-8.5), child abuse (OR = 2.8, 95%CI: 1.3-6.2), parental death (OR = 3.0, 95%CI: 1.2-7.5), and the score of the affective subscale in BPRS (OR = 1.7, 95%CI: 1.3-2.4) were significantly associated with dual-harm. CONCLUSIONS: Our study suggested the necessity of integrated evaluation of self-harm among individuals with serious aggressive behaviors. Childhood adversities and psychiatric symptoms in this population require special attention.

Structural Deficits in the Frontotemporal Network Associated With Psychopathic Traits in Violent Offenders With Schizophrenia.

People with schizophrenia (SZ) are at increased risk of violence compared to the general population. However, the neural mechanisms of violent behavior in patients with SZ are still unclear due to the heterogeneity of the diseased population. In this study, we aimed to examine the neural correlates of violent behavior in SZ and to determine whether the structural deficits were related to psychopathic traits. A total of 113 participants, including 31 SZ patients with violent behavior (vSZ), 39 SZ patients without violent behavior (nvSZ), and 43 healthy controls (HC), completed the T1-weighted magnetic resonance imaging (MRI) scan and were analyzed using voxel-based morphometry approach. The psychopathic traits were assessed using the Psychopathy Checklist: Screening Version (PCL:SV). The results showed decreased gray matter volume (GMV) in the vSZ group in the right temporal lobe and bilateral inferior frontal gyri compared to HCs; while reduced GMV in the inferior parietal lobe, parahippocampal and orbital frontal gyri was found in the nvSZ group compared with HCs. Correlation analyses showed that psychopathic traits were negatively associated with the GMV in the right superior temporal and left fusiform gyri in the vSZ group, indicating that psychopathic traits, as reflected by the score of antisocial factor, might be related to structural deficits in the temporal lobe, which led to a propensity to violent behavior in patients with SZ. Our findings suggest that violent behavior in patients with SZ might have a personality background associated with the frontotemporal network aberrance. In future studies, we need to take a closer look at psychopathic traits for better understanding of the mechanism of interpersonal violence in patients with SZ and to explore whether the imaging findings from this study can serve as a biomarker to predict future violent behaviors and community living.

Application of Ultrasound-Guided Transversus Abdominis Plane Block Combined with Nalbuphine Patient-Controlled Intravenous Analgesia in Postoperative Analgesia After Laparotomy: A Randomized Controlled Trial.

INTRODUCTION: Pain is a common postoperative complication. The ideal postoperative analgesia is awake, safe, mobile, and without side effects. The objective of this study is to provide new ideas for postoperative analgesia by observing the safety and analgesic effect of different analgesic methods in patients undergoing laparotomy after surgery. METHODS: Patients, who underwent laparotomy between September 2019 and December 2020, were randomly divided into three groups: group S received sufentanil, group N received nalbuphine, group T + N received postoperative bilateral transversus abdominis plane block (TAPB) and nalbuphine. The primary outcomes included visual analog scale (VAS) score and the use of postoperative analgesic pump. Secondary outcomes included quality of life recovery (QoR-15) scale score and incidence of postoperative adverse reactions. RESULTS: Compared with group S and N, there were significant differences in the resting VAS score within 48 h after surgery, dynamic VAS score within 12 h after surgery, the first compression time, and cumulative use of patient-controlled intravenous analgesia (PCIA) drugs at 24 h in group T + N (P < 0.05). The QoR-15 score within 48 h after surgery in group T + N was significantly higher than group N (P < 0.05). The first exhaust time and the incidence of nausea and vomiting in group T + N were significantly lower than those in group N (P < 0.05). CONCLUSIONS: Sufentanil PCIA and nalbuphine PCIA have equivalent analgesic effects, while TAPB combined with nalbuphine PCIA can ensure a good analgesic effect, thereby reducing the incidence of adverse reactions.

Long-term Weight Change and its Temporal Relation to Later-life Dementia in the Health and Retirement Study.

CONTEXT: Weight loss among middle-aged and older adults has been associated with a higher risk of subsequent dementia. However, most studies have limited follow-up durations or suboptimal control for the potential influence of physical frailty (PF). OBJECTIVE: Our study aimed to investigate the long-term and temporal relations of weight change to risk of dementia among middle-aged and older adults in the United States. METHODS: A total of 5985 participants aged 65 years and older were included from the Health and Retirement Study. History of long-term weight change was calculated using 9 repeated body mass index measurements during 1992-2008. We then followed participants' dementia status from 2008 to 2018. Multivariable Cox proportional hazard models were used. RESULTS: During the study follow-up period (mean = 7.54 years), a total of 682 (11.40%) dementia cases were documented. After adjustment for basic demographic and lifestyle factors, participants with weight loss (median: -0.23 kg/m2 per year) were at a significantly higher risk of dementia (HR = 1.60; 95% CI, 1.33, 1.92), compared with the stable weight group (median: 0.11 kg/m2 per year). This association was attenuated but remained strong and significant after further adjustment for PF (HR = 1.57; 95% CI, 1.30, 1.89). Significant association was observed for weight loss assessed approximately 14 to 18 years preceding dementia diagnosis (HR = 1.30; 95% CI, 1.07, 1.58), and was consistent closer to diagnosis. CONCLUSION: Both recent and remote weight loss were associated with a higher risk of later-life dementia among middle-aged and older adults independent of PF status.