Association between combination COVID-19-influenza vaccination and long COVID in middle-aged and older Europeans: A cross-sectional study.

The potential impact of combined COVID-19 and influenza vaccination on long COVID remains uncertain. In the present cross-sectional study, we aimed to investigate the plausible association between them in middle-aged and older Europeans based on the Survey of Health, Ageing, and Retirement in Europe (SHARE). A total of 1910 participants were recruited in the analyses. The study outcome was long COVID. Participants were divided into 4 groups through the self-reported status of COVID-19 and influenza vaccination. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. 1397 participants experienced long COVID. After multivariable adjustment, those vaccinated with neither COVID-19 nor influenza vaccine had higher risk of long COVID (OR, 1.72; 95% CI, 1.26-2.35) compared to those vaccinated with both vaccines. Furthermore, adding the 4 statuses of COVID-19 vaccination/influenza vaccination to conventional risk model improved risk reclassification for long COVID (continuous net reclassification improvement was 16.26% [p = .003], and integrated discrimination improvement was 0.51% [p = .005]). No heterogeneity was found in the subgroup analyses (all p-interaction ≥0.05). Our study might provide a strategy for people aged 50 and over to reduce the occurrence of long COVID, that is, to combine the use of the COVID-19 vaccine and influenza vaccines.

Combined influence of depression symptoms and ratio of triglyceride to high-density lipoprotein cholesterol on cardiometabolic multimorbidity: Findings from the China Health and Retirement Longitudinal Study 2011-2018.

BACKGROUND: Previous studies had reported depression symptoms and TG/HDLC ratio may share pathophysiological pathway. The aim was to investigate the combined effects of depression symptoms and TG/HDL-C ratio on the risk of CMM. METHODS: This cohort study extracted data from 2011 to 2018 of CHARLS. The CMM event occurred from 2013 to 2018, defined as suffering from more than one of stroke, cardiac events, and diabetes mellitus. Cox proportional hazards regression models were used to assess the association between the baseline combined effects of depression symptoms and TG/HDL-C ratio with incidence of CMM, stroke, cardiac events, and diabetes mellitus. RESULTS: A total of 8349 participants (3966 men and 4383 women) were included in the study, with a mean age of 58.5 years. During a 7-year follow-up survey, 370 (4.43 %) participants developed CMM. Compared to individuals with no depression symptoms and low TG/HDLC ratio, the multivariable-adjusted HRs (95%CI) for the new-onset CMM for patients with the depression symptoms alone, high TG/HDLC ratio alone, and depression symptoms and high TG/HDLC ratio were 1.37 (95 % CI = 0.95-1.98), 1.62 (95 % CI = 1.22-2.14), 1.94 (95 % CI = 1.39-2.72), respectively (P < 0.001). LIMITATIONS: Firstly, potential confounding factors such as dietary intake and nutrition were not collected at the time of study design. Secondly, exposure to the outcome was self-reported, which may cause recall bias or misclassification. Finally, the population was aged ≥45 years, so the results cannot be generalized to all age groups. CONCLUSION: Our findings indicated that patients with depression and high TG/HDLC ratio had a higher risk of developing CMM.

Early versus delayed antihypertensive treatment in patients with acute ischaemic stroke: multicentre, open label, randomised, controlled trial.

OBJECTIVES: To compared the effect of early antihypertensive treatment started within 24-48 h of stroke onset versus delaying treatment until day eight on reducing dependency or death. DESIGN: Multicentre, randomised, open label trial. SETTING: 106 hospitals in China between 13 June 2018 and 10 July 2022. PARTICIPANTS: 4810 patients (≥40 years) were enrolled with acute ischaemic stroke within 24-48 h of symptom onset and elevated systolic blood pressure between 140 mm Hg and <220 mm Hg. INTERVENTIONS: Patients were randomly assigned to receive antihypertensive treatment immediately after randomisation (aimed at reducing systolic blood pressure by 10%-20% within the first 24 h and a mean blood pressure <140/90 mm Hg within seven days) or to discontinue antihypertensive medications for seven days if they were taking them, and then receive treatment on day 8 (aimed at achieving mean blood pressure <140/90 mm Hg). MAIN OUTCOME MEASURES: The primary outcome was the combination of functional dependency or death (modified Rankin scale score ≥3) at 90 days. Intention to treat analyses were conducted. RESULTS: 2413 patients were assigned to the early treatment group and 2397 were assigned to the delayed treatment group. Mean systolic blood pressure was reduced by 9.7% (from 162.9 mm Hg to 146.4 mm Hg) in the early treatment group and by 4.9% (from 162.8 mm Hg to 154.3 mm Hg) in the delayed treatment group within 24 h after randomisation (P for group difference <0.001). Mean systolic blood pressure was 139.1 mm Hg in the early treatment group and 150.9 mm Hg in the delayed treatment group on day seven (P for group difference <0.001). Additionally, 54.6% of patients in the early treatment group and 22.4% in the delayed treatment group had blood pressure of less than 140/90 mm Hg (P<0.001 for group difference) on day seven. At day 90, 289 trial participants (12.0%) in the early treatment group, compared with 250 (10.5%) in the delayed treatment group, had died or experienced a dependency (odds ratio 1.18 (95% confidence interval 0.98 to 1.41), P=0.08). No significant differences in recurrent stroke or adverse events were reported between the two groups. CONCLUSIONS: Among patients with mild-to-moderate acute ischaemic stroke and systolic blood pressure between 140 mm Hg and <220 mm Hg who did not receive intravenous thrombolytic treatment, early antihypertensive treatment did not reduce the odds of dependency or death at 90 days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03479554.

The association between long-term platelet count and disability-free survival among middle-aged and older Chinese: Evidence from the China Health and Retirement Longitudinal Study.

BACKGROUND AND AIMS: We aimed to assess the associations of baseline and long-term platelet count (PLT) with disability-free survival (DFS) among middle-aged and older Chinese. METHODS AND RESULTS: A total of 7296 participants were recruited in the analysis. Updated mean PLT was defined as the mean of the two PLT measurements (4 years between wave 1-3). The long-term status of PLT was defined as persistent low, attenuated, increased and persistent high PLT according to the optimal cut points from the receiver operating characteristic curves of the two PLT measurements, respectively. The primary outcome was DFS, evaluated by the first occurrence of either disability or mortality. During 6-year visit, 1579 participants experienced disability or all-cause mortality. The rates of primary outcome were significantly higher among participants with elevated baseline PLT and updated mean PLT. Multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of primary outcome were 1.253 (1.049-1.496) for highest baseline PLT tertile and 1.532 (1.124-2.088) for highest updated mean PLT tertile, comparing to the lowest tertiles. Multivariable-adjusted spline regression models showed a linear association of baseline PLT (plinearity < 0.001) and updated mean PLT (plinearity = 0.005) with primary outcome. Moreover, participants with persistent high PLT and increased PLT had increased risk of primary outcome (ORs [95% CIs]: 1.825 [1.282-2.597] and 1.767 [1.046-2.985], respectively), compared with the reference of those with persistent low PLT. CONCLUSION: This study proved elevated baseline PLT, especially long-term persist high or increased PLT was associated with less likelihood of DFS among middle-aged and older Chinese.

Combined effects of high sensitivity C-reactive protein and triglyceride-glucose index on risk of cardiovascular disease among middle-aged and older Chinese: Evidence from the China Health and Retirement Longitudinal Study.

BACKGROUND AND AIMS: High sensitivity C-reactive protein (hsCRP) and triglyceride glucose (TyG) index were proved to be independent risk factors of cardiovascular disease (CVD). However, individual hsCRP or TyG index might not provide sufficient predictive value on CVD risk. The current study aimed to evaluate the cumulative effect of hsCRP and TyG index on CVD risk prospectively. METHODS AND RESULTS: A total of 9626 participants were enrolled in the analysis. The TyG index was calculated as ln(triglyceride [mg/dL] × fasting glucose [mg/dL]/2). The primary outcome was new-onset CVD events (cardiac events or stroke), and the secondary outcomes were new-onset cardiac events and stroke, separately. Participants were divided into 4 groups through the median of hsCRP and TyG index. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportion hazard models. From 2013 to 2018, 1730 participants experienced CVD (570 stroke and 1306 cardiac events). Linear associations were found between hsCRP, TyG index, hsCRP/TyG ratio and CVD (all p < 0.05). Compared to participants with low hsCRP/low TyG index, multivariable adjusted HRs (95% CIs) for those with high hsCRP/high TyG index were 1.17 (1.03-1.37) for CVD. No interaction of hsCRP and TyG index was found on CVD (p-interaction ≥0.05). Furthermore, adding hsCRP and TyG index simultaneously to conventional risk model improved risk reclassification for CVD, stroke and cardiac events (all p < 0.05). CONCLUSION: The present study suggested combination of hsCRP and TyG index might better improved the ability for risk stratification of CVD among middle-aged and older Chinese.

Grip strength affects the association between platelet count and disability-free survival: Evidence from the China Health and Retirement Longitudinal Study.

BACKGROUND AND AIMS: Previous studies found elevated platelet count (PLT), especially long-term persist high or increased PLT was associated with less likelihood disability-free survival (DFS). However, whether grip strength affects the relationship between them is still not elucidated. METHODS: A total of 6252 participants were recruited in the analysis based on the China Health and Retirement Longitudinal Study. The primary outcome was DFS, evaluated by a composite endpoint based on the first occurrence of either disability (having difficulty in at least one of the 6 activities of daily living: namely, dressing, bathing, continence, eating, getting into or out of bed, and toileting) or all-cause mortality. RESULTS: The association of PLT with primary outcome was significantly modified by grip strength (pinteraction = 0.022). The rates of primary outcome were significantly lower among participants with lower baseline PLT in participants with normal grip strength (multivariable odds ratio [OR], 0.67; 95% confidence interval [CI], 0.54-0.84; ptrend < 0.001), but not in those with low grip strength (multivariable OR, 1.70; 95% CI, 0.88-3.15; ptrend = 0.135), for the lowest quartile vs the highest quartile. Adding baseline PLT (quartiles or continuous) to a model containing conventional risk factors significantly improved risk reclassification for primary outcome among those with normal grip strength (most of p < 0.05). CONCLUSION: An inverse dose-response association of PLT with DFS was found among participants with normal grip strength, but not among those with low grip strength. Low grip strength might weaken the benefit of low PLT on DFS among middle-aged and older Chinese.

Distinct depressive symptom trajectories are associated with incident diabetes among Chinese middle-aged and older adults: The China Health and Retirement Longitudinal Study.

OBJECTIVE: Previous studies have reported that depression and depressive symptom are associated with diabetes incident. However, the association between long-term depressive symptom patterns and risk of diabetes remains unknown. The aim of present study was to evaluate the association between depressive symptom trajectories and risk of diabetes. METHODS: We used data of 8806 participants (≥45 years old) from the China Health and Retirement Longitudinal Study (CHARLS). Trajectories of depressive symptom were identified by latent mixture modeling. Multivariable logistic regression model was used to examine the association of depressive symptom trajectories with diabetes. RESULTS: Five depressive symptom trajectories were identified, characterizing by maintaining a low CES-D scores throughout the follow-up (low-stable; 3227 participants [36.65%]); maintaining a moderate CES-D scores throughout the follow-up (moderate-stable; 3402 participants [38.63%]); moderate starting CES-D scores then increasing scores (moderate-increasing; 681 participants [7.73%%]); high starting CES-D scores but then decreasing scores (high-decreasing; 1061 participants [12.05%]); and maintained high CES-D scores throughout the follow-up (high-stable; 435 participants [4.94%]). During 2015 to 2018 (Wave 3 to Wave 4), a total of 312 respondents experienced diabetes. Compared with participants in the low-stable depressive symptom trajectory, those following a high-decreasing (ORs = 2.04; 95%CIs 1.48-2.98) and high-stable depressive symptom trajectories (ORs = 3.26; 95%CIs 2.06-5.16) were at substantially higher risk of developing diabetes. CONCLUSIONS: Individuals with high-decreasing and high-stable depressive symptom trajectories over time were associated with increased risk of incident diabetes. Long-term depressive symptom may be a strong predictor of having diabetes.

Hypertension, remnant cholesterol and cardiovascular disease: evidence from the China health and retirement longitudinal study.

OBJECTIVE: Previous studies had reported the significant association between hypertension, remnant cholesterol (RC) and risk of cardiovascular disease (CVD). The aim of present study was to evaluate the combined effect of hypertension and RC on the risk of CVD. METHODS: A total of 9456 participants from the China Health and Retirement Longitudinal Study were included. Multivariate Cox proportional hazards regression model was used to explore the associations between hypertension, RC and new-onset CVD, stroke and cardiac events. RESULTS: During the follow-up period, 1702 CVD events (including 563 stroke and 1282 cardiac events) were recorded. Compared to those without hypertension and low RC level, the adjusted hazard ratios (95% confidence intervals) were 1.09 (0.95-1.24) for individuals with high RC alone, 1.27 (1.10-1.46) for individuals with hypertension alone and 1.32 (1.15-1.51) for individuals with comorbid hypertension and high RC. Individuals with co-existence of hypertension and high RC also had the highest risks of stroke and cardiac events. CONCLUSION: Our study indicated that there was a combined effect of hypertension and RC on the risk of CVD, stroke and cardiac events. Larger-sample prospective cohort studies are still required to test the potential application of combination of hypertension and RC as a screening method to identify individuals at risk of CVD.

Prospective bidirectional associations between depression and chronic kidney diseases.

Previous studies had reported the mutual relation between depression and chronic kidney diseases (CKD). This study aimed to investigate potential bidirectional relationships between depression and CKD. Participants more than 45 years from the China Health and Retirement Longitudinal Study (CHARLS) were included in present study. In study I, we tended to assess the association between baseline depression with the risk of subsequent CKD. In study II, we aimed to examine whether the onset of CKD could predict the development of depression. Multivariate logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) in study I and study II, respectively. In study I, 301 (6.16%) respondents experienced CKD in participants without depression, and 233 (8.48%) respondents experienced CKD in participants with depression. Participants with depression had higher risk of developing CKD with the corresponding ORs (95% CIs) was 1.38(1.08-1.76). In study II, 1333 (22.29%) subjects in the non-CKD group and 97 (27.17%) in CKD group developed depressive symptoms. Individuals with CKD had higher risk of developing depression than those without CKD, with the multivariate ORs (95% CIs) was 1.48(1.23-1.78). Significant bidirectional relationships remained in both sensitivity and subgroup analyses. Findings demonstrate bidirectional relationships between depression and CKD. Individuals with depression were associated with increasing risk of CKD; in addition, CKD patients had higher risk of developing depression.

Association between visceral adiposity index and chronic kidney disease: Evidence from the China Health and Retirement Longitudinal Study.

BACKGROUND AND AIMS: The association between visceral adiposity index (VAI) and chronic kidney disease (CKD) remains debatable. We aimed to prospectively investigate the relationship between VAI and CKD. METHODS AND RESULTS: A total of 8808 participants from the China Health and Retirement Longitudinal Study were included. Males and females were divided into four groups according to gender-specific quartiles of VAI scores. CKD was based on self-reported physicians' diagnosis or personal eGFR level. A logistic regression model was established to analyze the correlation between VAI and CKD. A meta-analysis was conducted to incorporate the results of the current study and previous studies on the association of VAI with CKD. During 7 years of follow-up, a total of 826 participants (9.38%) experienced CKD. In multivariable-adjusted analyses, the adjusted odds ratios (95% confidence intervals) for the highest versus lowest quartile of VAI was 1.33 (1.03-1.77) for male, and 1.10 (0.81-1.48) for female, respectively. The meta-analysis found the significant associations between VAI and CKD in total, male and female participants (pooled relative risk for highest vs lowest VAI quartile were 2.24(1.70-2.95), 2.36(1.54-3.61) and 2.57 (1.57-4.22), respectively). CONCLUSIONS: Higher VAI score was associated with increased risk of CKD, independently of established risk factors. The VAI may be a predictor of incident CKD, but only among male participants based on present study.

Trajectories of depressive symptoms and risk of cardiovascular disease: Evidence from the China Health and Retirement Longitudinal Study.

BACKGROUND: Previous studies have reported that depression is associated with higher risk of cardiovascular disease (CVD). However, the association between long-term depressive symptom patterns and the risk of CVD was not well characterized. METHODS: A total of 8621 participants with three Center for Epidemiological Studies Depression Scale (CES-D) measurements from the China Health and Retirement Longitudinal Study were included. Trajectories of depressive symptoms were identified by latent mixture modeling. Cox proportional hazards regression models were used to examine the association of depressive symptom trajectories with CVD (stroke or cardiac events), and accounting for mortality as a competing risk for CVD. RESULTS: We identified four distinct depressive symptoms trajectories, characterized by maintaining low CES-D score throughout the follow-up (no depressive symptoms; 5642 participants [65.44%]); high starting CES-D scores but then decreasing scores (decreasing depressive symptoms; 1329 participants [14.91%]); low starting CES-D scores then increasing scores (increasing depressive symptoms; 1154 participants [13.39%]) and maintained high CES-D scores throughout the follow-up (persistent depressive symptoms; 496 participants [6.26%]). During the follow-up period, 853 CVD events (including 362 strokes and 535 cardiac events) were recorded. Compared to participants in the no depressive symptom trajectory, those in the increasing depressive symptoms and persistent depressive symptom trajectories had an increased risk of CVD, with multiple-adjusted hazard ratios (95% confidence intervals) of 1.53 (1.28-1.82) and 1.68 (1.34-2.12), respectively. Individuals with increasing and persistent depressive symptoms trajectories also had higher risks of stroke and cardiac events. CONCLUSIONS: Individuals with increasing and persistent depressive symptom over time were associated with increased risk of incident CVD.

China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2): rationale and design.

BACKGROUNDS: Increased blood pressure (BP) for patients who had an acute ischaemic stroke is associated with poor functional outcome, however the optimal timing of antihypertensive therapy is unknown. AIMS: We aim to compare early antihypertensive treatment to delayed antihypertensive treatment for reducing the risk of composite major disability and mortality at 3 months in acute ischaemic stroke. DESIGN: The China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2) trial is a multicentre, randomised, open-label, blinded-endpoints trial that will be conducted in 100 hospitals in China. The primary outcome is the composite of death and major disability (modified Rankin Scale score ≥3) at 3 months of randomisation. Antihypertensive treatment will be received immediately after randomisation in the early treatment group, aimed at average systolic BP by 10%-20% reduction within the first 24 hours, and achieving an average BP level of <140/90 mm Hg within 5 days. Patients in the delayed treatment group will discontinue any antihypertension medications for the first 7 days of randomisation, and will receive antihypertensive therapy achieving a BP goal of <140/90 mm Hg after 7 days. CONCLUSION: The CATIS-2 trial will be testing the hypotheses that early BP lowering leads to improved functional outcome without any other harms, and developing clinical guidelines of the BP management for patients who had an acute ischaemic stroke. TRIAL REGISTRATION NUMBER: NCT03479554.

Angiopoietin-like protein 4 and clinical outcomes in ischemic stroke patients.

AIMS: Angiopoietin-like protein 4 (ANGPTL-4) had been reported to be associated with the risk of ischemic stroke, but its prognostic value remained unclear. The aim of this study was to investigate the association between plasma ANGPTL-4 concentrations and prognosis of ischemic stroke. METHODS: Baseline plasma ANGPTL-4 concentrations were measured in 3379 acute ischemic stroke patients. The primary outcome was a combination of death or major disability (modified Rankin Scale score, ≥3) at 3 months after ischemic stroke. RESULTS: At 3 months after ischemic stroke, 850 (26.16%) participants experienced major disability or died (750 major disabilities and 100 deaths). After adjusting for important covariates, odds ratios for the highest tertile of plasma ANGPTL-4 concentrations were 1.59 (1.22-2.06) for primary outcome, 1.53 (1.18-1.97) for major disability, and 2.03 (1.03-4.00) for death when compared with the lowest tertile of plasma ANGPTL-4 concentrations. For 1-SD increase in log-ANGPTL-4 concentrations (0.44 ng/mL), the adjusted odds ratios were 1.24 (1.11-1.38), 1.14 (1.03-1.27), and 1.72 (1.32-2.23), respectively. Adding ANGPTL-4 to a model containing conventional risk factors improved risk prediction for composite outcome of death and major disability. CONCLUSION: Higher plasma ANGPTL-4 concentration was associated with poor prognosis in acute ischemic stroke patients, suggesting that ANGPTL-4 might be a prognostic marker for ischemic stroke.

Education Level and Long-term Mortality, Recurrent Stroke, and Cardiovascular Events in Patients With Ischemic Stroke.

Background Epidemiological studies have reported discrepant findings on the relationship between education level and outcomes after stroke. We aimed to prospectively investigate the relationship between education level and mortality, recurrent stroke, and cardiovascular events in Chinese patients with ischemic stroke. Methods and Results We included 3861 participants from the China Antihypertensive Trial in Acute Ischemic Stroke. Education level was categorized as illiteracy, primary school, middle school, and college. Study outcomes were all-cause mortality, stroke-specific mortality, recurrent stroke, and cardiovascular events within 2 years after ischemic stroke. A meta-analysis was conducted to incorporate the results of the current study and previous other studies on the association of education level with outcomes after stroke. Within 2 years after ischemic stroke, there were 327 (8.5%) all-cause deaths, 264 (6.8%) stroke-specific deaths, 303 (7.9%) recurrent strokes, and 364 (9.4%) cardiovascular events, respectively. The Kaplan-Meier curves showed that patients with the lowest education level had the highest cumulative incidence rates of all-cause mortality, stroke-specific mortality, and cardiovascular events (log-rank P≤0.01). After adjusted for covariates, hazard ratios and 95% CIs of illiteracy versus college education were 2.79 (1.32-5.87) for all-cause mortality, 3.68 (1.51-8.98) for stroke-specific mortality, 2.82 (1.20-6.60) for recurrent stroke, and 3.46 (1.50-7.95) for cardiovascular events. The meta-analysis confirmed the significant association between education status and mortality after stroke (pooled relative risk for lowest versus highest education level, 1.24 [95% CI, 1.05-1.46]). Conclusions Low education level was significantly associated with increased risk of mortality, recurrent stroke, and cardiovascular events after ischemic stroke, independently of established risk factors. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT01840072.

Influence of lipoprotein-associated phospholipase A2 mass on prognosis value of baseline platelet count for clinical outcomes after acute ischemic stroke.

BACKGROUND AND AIMS: We aimed to examine the association between baseline platelet count (PLT) and prognosis of acute ischemic stroke according to lipoprotein-associated phospholipase A2 (Lp-PLA2) mass. METHODS: A total of 3254 patients with acute ischemic stroke were included in this analysis. The primary outcome was a combination of major disability and all-cause mortality (modified Rankin Scale score ≥3) at 3 months after stroke. Secondary outcome was major disability and all-cause mortality, respectively. RESULTS: The prognosis value of PLT for primary outcome was significantly modified by Lp-PLA2 mass (pinteraction = 0.002). After multivariate adjustment, elevated PLT was associated with the increased risk of primary outcome in patients with high Lp-PLA2 mass (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.09-2.48; ptrend = 0.002), but not in those with low Lp-PLA2 mass (OR, 0.94; 95%CI, 0.62-1.42; ptrend = 0.181), when comparing two extreme PLT quartiles. A similar association was found between elevated PLT and major disability (pinteraction = 0.001). Elevated PLT was associated with increased risk of major disability only in patients with high Lp-PLA2 mass (OR, 1.54; 95%CI, 1.03-2.31; ptrend = 0.007), for the highest quartile vs the lowest quartile. Each 100 × 109/L increment in PLT was associated with 42% (95%CI, 12%-79%) increased risk of primary outcome and 33% (95%CI, 6%-68%) increased risk of major disability in those with high Lp-PLA2 mass. CONCLUSIONS: The elevated PLT was associated with poor prognosis of acute ischemic stroke only in patients with high Lp-PLA2 mass. Lp-PLA2 might be an important factor influencing the prognosis value of PLT for clinical outcomes in acute ischemic stroke patients.

Diabetes-induced central neuritic dystrophy and cognitive deficits are associated with the formation of oligomeric reticulon-3 via oxidative stress.

Diabetes is a high risk factor to dementia. To investigate the molecular mechanism of diabetic dementia, we induced type 2 diabetes in rats and examined potential changes in their cognitive functions and the neural morphology of the brains. We found that the diabetic rats with an impairment of spatial learning and memory showed the occurrence of RTN3-immunoreactive dystrophic neurites in the cortex. Biochemical examinations revealed the increase of a high molecular weight form of RTN3 (HW-RTN3) in diabetic brains. The corresponding decrease of monomeric RTN3 was correlated with the reduction of its inhibitory effects on the activity of ß-secretase (BACE1), a key enzyme for generation of ß-amyloid peptides. The results from immunoprecipitation combined with protein carbonyl detection showed that carbonylated RTN3 was significantly higher in cortical tissues of diabetic rats compared with control rats, indicating that diabetes-induced oxidative stress led to RTN3 oxidative damage. In neuroblastoma SH-SY5Y cells, high glucose and/or H2O2 treatment significantly increased the amounts of carbonylated proteins and HW-RTN3, whereas monomeric RTN3 was reduced. Hence, we conclude that diabetes-induced cognitive deficits and central neuritic dystrophy are correlated with the formation of aggregated RTN3 via oxidative stress. We provided the first evidence that oxidative damage caused the formation of toxic RTN3 aggregates, which participated in the pathogenesis of central neuritic dystrophy in diabetic brain. Present findings may offer a new therapeutic strategy to prevent or reduce diabetic dementia.