OBJECTIVES: To investigate the associations between Tau protein deposition and brain biochemical metabolites detected by proton magnetic resonance spectroscopy (¹H-MRS) in patients with advanced Alzheimer's disease (AD). METHODS: From April, 2022 to December, 2024, 64 Tau-positive AD patients and 29 healthy individuals underwent ¹⁸F-APN-1607 PET/MR and simultaneously acquired multi-voxel ¹H-MRS in the Department of Nuclear Medicine, Nanjing First Hospital. Visual analysis and voxel-based analysis of PET/MR data were performed to investigate the Tau protein deposition patterns in AD patients. Valid voxels within the ¹H-MRS field of view were selected, and their standardized uptake value ratio (SUVr) in PET and metabolite levels of N-acetylaspartate (NAA), choline (Cho), creatine (Cr), NAA/Cr, and Cho/Cr were recorded. The Tau-positive (Tau⁺) voxels and Tau-negative (Tau^-) voxels of the AD patients were compared for PET and ¹H-MRS parameters, and the correlations between the metabolites and Tau PET SUVr within Tau⁺ voxels were analyzed. RESULTS: Significant Tau protein deposition were observed in the AD patients, involving mainly the bilateral frontal lobes (30.07%), parietal lobes (29.96%), temporal lobes (21.07%), and occipital lobes (15.89%). A total of 1422 valid voxels in AD group (including 994 Tau⁺ and 428 Tau^- voxels) and 814 voxels in the control group were selected. The AD patients showed significantly decreased NAA level and increased SUVr compared with the control group (P<0.05). Subgroup analyses revealed that Tau⁺ voxels had higher SUVr and lower Cr and Cho/Cr than Tau^- voxels (P<0.05). Compared with the control group, Tau⁺ voxels exhibited higher SUVr and lower Cr (P<0.05), while Tau^- voxels showed lower NAA (P=0.004). No significant differences were found in Cho or NAA/Cr among the subgroups (P>0.05). Within Tau⁺ voxels, NAA, Cho, and Cr were negatively correlated with SUVr (P<0.001). CONCLUSIONS The patients with progressive AD have significant Tau protein deposition in the brain, which is correlated with alterations in metabolite levels. Decreased NAA is more prominent in early or pre-tau deposition stages, while Cr changes is more significant in the regions with Tau protein deposition, suggesting the potential of NAA and Cr as biomarkers for Tau protein deposition in AD for disease monitoring and treatment evaluation.
Humans ; Alzheimer Disease/diagnostic imaging* ; Aspartic Acid/metabolism* ; tau Proteins/metabolism* ; Creatine/metabolism* ; Brain/metabolism* ; Biomarkers/metabolism* ; Positron-Emission Tomography ; Male ; Female ; Proton Magnetic Resonance Spectroscopy ; Choline/metabolism* ; Aged ; Middle Aged

Objective:To investigate the predictive value of inflammatory markers for the risk of stroke-associated infection (SAI) in patients with anterior circulation large vessel occlusive stroke who received endovascular therapy.Methods:Patients with anterior circulation large vessel occlusive stroke received endovascular treatment in Nanjing First Hospital, Nanjing Medical University from 2016 to 2020 were retrospectively enrolled. The clinical data of SAI group and non-SAI group were compared. Multivariate logistic regression analysis was used to screen the independent influencing factors of SAI, and then the predictive nomogram was established according to these influencing factors to verify its clinical application efficiency. Results:A total of 409 patients were enrolled during the study. Their age was 71.3±11.7 years, and 250 were male (61.1%). The median baseline Naitonal Institutes of Health Stroke Scale (NIHSS) score was 16. One hundred and nineteen patients (29.1%) received intravenous thrombolysis, 376 (91.9%) were successfully recanalized after endovascular therapy, and 293 (71.6%) developed SAI. Univariate analysis showed that age, atrial fibrillation ratio, NIHSS score at admission, fasting blood glucose, triglyceride, high sensitivity C reactive protein (hs-CRP), leukocyte count, neutrophil count, neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were significantly higher than those in the non-SAI group (all P<0.05). Multivariate logistic regression analysis showed that age, NIHSS score at admission, fasting blood glucose, hs-CRP, leukocyte count, neutrophil count and NLR were the independent influencing factors of SAI ( P<0.05). Receiver operating characteristics curve analysis showed that the predictive value of multiple inflammatory markers (hs-CRP, leukocyte count, neutrophil count and NLR) for SAI was significantly better than that of the single inflammatory marker ( P<0.01). The area under the curve was 0.782 (95% confidence interval 0.719-0.846), and the predictive sensitivity and specificity were 80.6% and 64.5% respectively. Decision curve analysis showed that compared with the traditional indicators, the predictive nomogram based on inflammation related indicators (hs-CRP, leukocyte count and NLR) had a higher net profitability for predicting SAI. Conclusion:The hs-CRP, leukocyte count and NLR can be used to predict the risks of SAI in patients with acute ischemic stroke receiving endovascular therapy.

Objective:To investigate the predictive values of serum hypersensitive C-reactive protein (hs-CRP) and lipoprotein-associated phospholipase A 2 (Lp-PLA 2) for early neurological deterioration (END) and parenchymal hematoma (PH)-type 2 hemorrhagic transformation (HT) after intravenous thrombolysis in patients with acute ischemic stroke. Methods:Patients with acute ischemic stroke treated with intravenous thrombolysis in the Department of Neurology, Nanjing First Hospital, Nanjing Medical University from January 2018 to January 2021 were enrolled retrospectively. END was defined as an increase of ≥4 in the National Institutes of Health Stroke Scale (NIHSS) score at 24 h after thrombolysis compared with the baseline. PH-2 type HT was defined as parenchymal hematoma with obvious space occupying effect or hemorrhage at the distant site of infarct. Multivariate logistic regression analysis was used to determine the independent influencing factors of END and PH-2 type HT. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of hs-CRP and Lp-PLA 2 levels for END and PH-2 type HT. Results:A total of 804 patients with acute ischemic stroke treated with intravenous thrombolysis were included, of which 63 (7.8%) developed END within 24 h after intravenous thrombolysis; 41 (5.1%) developed HT, of which 38 were PH-2 type HT. Univariate analysis showed that the levels of serum hs-CRP and Lp-PLA 2 in the END group were significantly higher than those in the non-END group (all P<0.05), and the levels of serum hs-CRP and Lp-PLA 2 in the PH-2 HT group were significantly higher than those in the non-PH-2 HT group ( P<0.05). Multivariate logistic analysis showed that hs-CRP (odds ratio [ OR] 1.017, 95% confidence interval [ CI] 1.001-1.034; P=0.043) and Lp-PLA 2 ( OR 1.002, 95% CI 1.000-1.003; P=0.020) were the independent risk factors for END after intravenous thrombolysis. In addition, hs-CRP ( OR 1.019, 95% CI 1.002-1.036; P=0.027) and Lp-PLA 2 ( OR 1.002, 95% CI 1.000-1.003; P=0.018) were also the independent risk factors for PH-2 HT after intravenous thrombolysis. The ROC curve analysis showed that the areas under the curve of hs-CRP and Lp-PLA 2 for predicting END were 0.675 (95% CI 0.609-0.741; P<0.001) and 0.606 (95% CI 0.528-0.683; P=0.005) respectively, and the areas under the curve for predicting PH-2 HT were 0.641 (95% CI 0.545-0.737; P=0.003) and 0.600 (95% CI 0.500-0.699; P= 0.051) respectively. Conclusion:Higher baseline serum hs-CRP and Lp-PLA 2 are the independent predictors of END and PH-2 type HT after intravenous thrombolysis in patients with acute ischemic stroke.

Objective:To investigate the correlation between fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVHs) and outcomes after endovascular mechanical thrombectomy (EMT) in patients with anterior circulation large vessel occlusive stroke.Methods:Using " Nanjing First Hospital Stroke Database" , consecutive patients with anterior circulation large vessel occlusive stroke received EMT treatment from June 2015 to December 2018 were enrolled retrospectively. Before EMT treatment, the distal FVH grade and the American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral circulation grade were evaluated. The modified Rankin Scale was used to evaluate the functional outcome of patients at 3 months after onset, and 0-2 was defined as a good outcome. Spearman correlation analysis was used to analyze the correlation between the distal FVH grade and the ASITN/SIR collateral circulation grade. Multivariate logistic regression analysis was used to identify the independent predictors of the outcomes. Results:A total of 117 patients with acute anterior circulation large vessel occlusive stroke were enrolled, aged 70.74±12.50 years, 72 (61.5%) were male. The baseline National Institutes of Health Stroke Scale (NIHSS) score was 13.73±4.91. Seventy-four patients (63.2%) had a good outcome and 43 (36.8%) had a poor outcome. The distal FVH grade was grade 0 in 8 cases (6.84%), grade 1 in 34 cases (29.06%), and grade 2 in 75 cases (64.10%). Compared with the distal FVH low-grade group (grade 0-1), the high-grade group (grade 2) had a higher ASITN/SIR collateral circulation grade ( P<0.001) and lower baseline National Institutes of Health Stroke Scale (NIHSS) score ( P=0.026). Spearman correlation analysis showed that the distal FVH grade was significantly positively correlated with the ASITN/SIR collateral circulation grade ( r=0.620, P<0.001). Multivariate logistic regression analysis showed that the high distal FVH grade (odds ratio [ OR] 0.336, 95% confidence interval [ CI] 0.128-0.879; P=0.026) was independently associated with the good outcomes, while the higher baseline NIHSS score ( OR 1.036, 95% CI 0.988-1.229; P=0.048) and symptomatic cerebral hemorrhage ( OR 5.597, 95% CI 1.052-29.761; P=0.043) were independently associated with the poor outcomes. Conclusion:The distal FVHs can reflect the state of collateral circulation. The high grade of distal FVHs is associated with the good outcomes after EMT in patients with anterior circulation large vessel occlusive stroke.

Objective To investigate the predictive value of serum lipoprotein (a) (Lp [a]) levels for short-term functional outcomes in elderly patients with acute ischemic stroke and type 2 diabetes mellitus.Methods Elderly patients with acute ischemic stroke and type 2 diabetes mellitus admitted to Nanjing First Hospital from June 2016 to December 2016 were enrolled retrospectively.The modified Rankin scale was used to assess the outcomes at 90 d after onset;0-2 was defined as good outcome and ＞2 were defined as poor outcome.Multivariate logistic regression analysis was used to determine independent risk factors for poor outcomes,and the receiver operator characteristic (ROC) curve analysis was used to evaluate the predictive value of serum Lp(a) levels for poor outcomes.Results A total of 231 patients were enrolled,with an average age of 69.7 years and males accounting for 65.4％.The median serum Lp(a) was 166 mg/L (interquartile range 78-331 mg/L).At 90 d after onset,140 patients (60.6％) had good outcomes and 91 (39.4％) had poor outcomes.After adjustment for other confounding variables,multivariate logistic regression analysis showed that elevated serum Lp(a) (referenced to the lowest quartile,the 3rd quartile:odds ratio[OR]2.899,95％ confidence interval[CI] 1.154-7.285,P =0.024;the 4th quartile:OR 3.334,95％ CI 1.329-8.361,P =0.010),the baseline National Institute of Health Stroke Scale score (OR 1.224,95％ CI 1.143-1.310;P＜ 0.001),and complicated with coronary heart disease (OR 2.504,95％ CI 1.196-5.243;P =0.015) were the independent risk factors for poor outcomes.ROC curve analysis showed that the area under the curve of serum Lp(a) level in predicting the poor outcome was 0.775 (95％ CI 0.696-0.854;P=0.04).The optimal cut-off value was 119 mg/L,the sensitivity was 71.15％,the specificity was 75.90％,the positive predictive value was 38.52％,and the negative predictive value was 61.48％.Conclusion Serum Lp(a) level has certain predictive value for the short-term poor outcomes in elderly patients with acute ischemic stroke and type 2 diabetes mellitus.

Objective: To investigate the correlations of serum uric acid with outcomes and symptomatic intracranial hemorrhage (sICH) after intravascular mechanical thrombectomy bridged with intravenous thrombolysis in patients with ischemic stroke. Methods: From January 2015 to January 2019, patients with acute ischemic stroke admitted to Nanjing First Hospital, Nanjing Medical University and underwent intravascular mechanical thrombectomy bridged with intravenous thrombolysis were analyzed retrospectively. Demographic characteristics, vascular risk factors, laboratory findings, National Institutes of Health Stroke Scale (NIHSS) scores, onset to treatment time, and whether sICH occurred were recorded. The modified Rankin Scale was used to evaluate the outcomes at 90 d after onset, and 0 to 2 was defined as good outcome. Multivariate logistic regression models were used to determine the independent factors for outcomes and sICH. Results: A total of 144 patients were included, 54 (37.5%) had a good outcome, 90 (62.5%) had a poor outcome (including 28 deaths), and 29 (20.1%) had sICH. Serum uric acid was significantly higher in the good outcome group than in the poor outcome group (P<0.05). Serum uric acid was significantly higher in the non-sICH group than in the sICH group (P<0.05). Multivariate logistic regression analysis showed that higher serum uric acid were the independent protective factors of good outcome (odds ratio 0.82, 95% confidence interval 0.66-0.93; P<0.001) and sICH (odds ratio 0.97, 95% confidence interval 0.93-0.99; P=0.004). Conclusion High serum uric acid level is independently associated with good outcome after intravascular mechanical thrombectomybridged with intravenous thrombolysis in patients with acute ischemic stroke.

Objective: To investigate the effect of the time from onset to recanalization on the outcomes after endovascular treatment (EVT) in patients with acute stroke due to posterior circulation large vessel occlusion. Methods: From May 2015 to May 2019, patients with acute ischemic stroke due to posterior circulation large vessel occlusion receiving EVT in the Department of Neurology, Nanjing First Hospital, Nanjing Medical University were enrolled retrospectively. According to the modified Rankin Scale (mRS) score at 90 d after procedure, they were divided into good outcome group (≤2) and poor outcome group (>2). Demographic and clinical data were compared between the two groups. Multivariate logistic regression analysis was used to determine the independent correlation between the time from onset to recanalization and the outcomes. Results: A total of 64 patients with acute ischemic stroke due to posterior circulation large vessel occlusion treated by EVT were enrolled in this study. There were 50 males (78.0%) and 14 females (22.0%). The age was 67.52±10.30 years. The National Institutes of Health Stroke Scale (NIHSS) score was 22.04±4.17, and the time from onset to recanalization was 370.53±78.59 min. Thirty-one patients (48.0%) were in the good outcome group and 33 (52.0%) were in the poor outcome group. There were significant differences in baseline NIHSS score, systolic blood pressure, time from onset to revascularization, and the proportions of patients with tandem lesion and symptomatic intracranial hemorrhage between the two groups (all P<0.05). Multivariate logistic regression analysis showed that the longer time from onset to recanalization (odds ratio [OR] 1.317, 95% confidence interval [CI] 1.001-3.034; P=0.041) and symptomatic intracranial hemorrhage (OR 4.207, 95% CI 1.931-10.761; P=0.004) were the independent predictors of poor outcomes, while the lower baseline NIHSS score (OR 0.302, 95% CI 0.056-0.743; P=0.047) was the independent protective factor of poor outcomes. Conclusions The longer time from onset to recanalization is an independent risk factor for poor outcomes after EVT in patients with acute ischemic stroke caused by posterior circulation large vessel occlusion.

Objective To compare the effects of intensive blood pressure (BP) lowering and guideline-recommended standard BP lowering on the early reperfusion and prognosis after intravenous thrombolysis in patients with acute ischemic stroke. Methods This is a randomised controlled trial consisting of 118 consecutive patients who came from Department of Neurology, Nanjing First Hospital from July 2012 to April 2016, accepting intravenous recombinant tissue plasminogen activator thrombolysis with the systolic blood pressure (SBP) being 150-185 mmHg(1 mmHg=0.133 kPa). The patients with ischemic stroke were diagnosed by multi-mode MRI and confirmed to have ischemic penumbra. The SBP of patients randomly assigned to intensive BP lowering group and guideline BP lowering group was maintained in 140-150 mmHg or below 180 mmHg respectively for 72 h and all patients needed to reexamine multi-mode MRI at 24 h. The primary endpoints were the neurologic function at early stage, modified Rankin Scale (mRS) score and the mortality at 90 d;the secondary endpoints were the volume of infarction and hypoperfusion area, the rate of reperfusion, hemorrhagic transformation (HT) and syptomatic intracerebral hemorrhage (sICH). Results Forty-nine cases in intensive BP lowering group and 56 cases in guideline BP lowering group acquired the available images. The volume of infarction was increased both in these two groups, and there was no statistically significant difference in the increased values ((13.21±9.51) cm3 vs (12.95±9.68) cm3). There were no statistically significant differences in the volume of hypoperfusion, reperfusion rate, neurologic function at early stage, the mRS scores and mortality at 90 d, the incidence of sICH except the rate of HT (9.4%, 5/53 vs 23.1%, 15/65, χ2=3.860, P=0.049) between the two groups.Conclusion Early intensive BP-lowering treatment has no adverse effects on the transformation of ischemic penumbra and prognosis after intravenous thrombolysis in patients with acute ischemic stroke and may decrease the the rate of HT in some degree.

Objective To investigate the effects of intensive antihypertensive treatment and guidelinerecommended standard blood pressure control on early reperfusion and outcomes after intravenous recombinant tissue plasminogen activator (rtPA) thrombolysis in patients with acute ischemic stroke.Methods A total of 50 patients with acute ischemic stroke (systolic blood pressure,150-185 mmHg;1 mmHg=0.133 kPa) and received intravenous rtPA therapy were enrolled prospectively.They were randomly divided into either a intensive antihypertensive treatment group or a guideline antihypertensive treatment group.In the the intensive antihypertensive treatment group,systolic blood pressure was decreased to 140-150 mmHg in 60 min for at least 72 h.In the guideline antihypertensive treatment group,systolic blood pressure was decreased to the target value ＜ 180 mmHg according to the guideline recommendation.Multi-mode MRI was completed at 24 h before and after thrombolysis.The primary endpoints were the modified Rankin Scale (mRS) score at day 90 and the mortality at day 90;the secondary endpoints were the early reperfusion rate in ischemic brain tissue,recanalization rate,and incidence of symptomatic intracranial hemorrhage.Results There was no significant difference in demographics and baseline data between the 2 groups.Within 24,48,and 72 h after thrombolysis the mean systolic blood pressure in the intensive antihypertensive treatment group was significantly lower than those in the guideline antihypertensive treatment group,while there was no significant difference in diastolic blood pressure.There were no significant differences in favorable outcome rate at day 90 (mRS score 0-2:68％ vs.64％;x2 =0-089,P=0.765),mortality (4％ vs.12％;x2 =1.087,P=0.297),incidence of symptomatic intracranial hemorrhage (4％ vs.8％;x2 =0.355,P =0.552),reperfusion rate after thrombolysis (76％ vs.68％;x2 =0.397,P =0.529),and recanalization rate (56％ vs.52％;x2 =0.081,P =0.777) between the intensive antihypertensive treatment group and the guideline antihypertensive treatment group.Conclusions Early intensive antihypertensive treatment in patients with acute ischemic stroke received intravenous rtPA thrombolysis does not have adverse effect on reperfusion rate,and does not increase the risk of death or disability either.