Association between healthy lifestyle and memory decline in older adults: 10 year, population based, prospective cohort study.

OBJECTIVE: To identify an optimal lifestyle profile to protect against memory loss in older individuals. DESIGN: Population based, prospective cohort study. SETTING: Participants from areas representative of the north, south, and west of China. PARTICIPANTS: Individuals aged 60 years or older who had normal cognition and underwent apolipoprotein E (APOE) genotyping at baseline in 2009. MAIN OUTCOME MEASURES: Participants were followed up until death, discontinuation, or 26 December 2019. Six healthy lifestyle factors were assessed: a healthy diet (adherence to the recommended intake of at least 7 of 12 eligible food items), regular physical exercise (≥150 min of moderate intensity or ≥75 min of vigorous intensity, per week), active social contact (≥twice per week), active cognitive activity (≥twice per week), never or previously smoked, and never drinking alcohol. Participants were categorised into the favourable group if they had four to six healthy lifestyle factors, into the average group for two to three factors, and into the unfavourable group for zero to one factor. Memory function was assessed using the World Health Organization/University of California-Los Angeles Auditory Verbal Learning Test, and global cognition was assessed via the Mini-Mental State Examination. Linear mixed models were used to explore the impact of lifestyle factors on memory in the study sample. RESULTS: 29 072 participants were included (mean age of 72.23 years; 48.54% (n=14 113) were women; and 20.43% (n=5939) were APOE ε4 carriers). Over the 10 year follow-up period (2009-19), participants in the favourable group had slower memory decline than those in the unfavourable group (by 0.028 points/year, 95% confidence interval 0.023 to 0.032, P<0.001). APOE ε4 carriers with favourable (0.027, 95% confidence interval 0.023 to 0.031) and average (0.014, 0.010 to 0.019) lifestyles exhibited a slower memory decline than those with unfavourable lifestyles. Among people who were not carriers of APOE ε4, similar results were observed among participants in the favourable (0.029 points/year, 95% confidence interval 0.019 to 0.039) and average (0.019, 0.011 to 0.027) groups compared with those in the unfavourable group. APOE ε4 status and lifestyle profiles did not show a significant interaction effect on memory decline (P=0.52). CONCLUSION: A healthy lifestyle is associated with slower memory decline, even in the presence of the APOE ε4 allele. This study might offer important information to protect older adults against memory decline. TRIAL REGISTRATION: ClinicalTrials.gov NCT03653156.

The Effect of Triggering Receptor Expressed by Myeloid Cells 2 Modified Bone Marrow Mesenchymal Stem Cells on Alzheimer's Disease-Mouse Model.

OBJECTIVE: This study aims to explore the effect of TREM2 modified BMSCs on hippocampus of AD mice. METHODS: Mouse bone marrow mesenchymal stem cells were isolated and identified. APP/PS1 double transgenic mice were confirmed to be AD model and divided into 4 groups: control group, MSCs group, MSCs+vector group and MSCs+pEGFP-TREM2 group. RESULTS: The incubation period and the number of errors in the MSCs+pEGFP-TREM2 group were significantly decreased than that of control group after 3 days. The quantity and area of Aß deposition in MSCs+pEGFP-TREM2 group were significantly smaller than that of control group. Aß40 and Aß42 levels were significantly decreased most in MSCs+pEGFP-TREM2 group. The expression levels of TREM2 and DAP12 significantly increased in the MSCs+pEGFP-TREM2 group. CONCLUSIONS: TREM2 modified bone marrow MSCs affected the ability of learning and memory of AD model mice and this mechanism may be related to the expression of TREM2 and DAP12 genes.

A Diagnostic Formula for Discrimination of Tuberculous and Bacterial Meningitis Using Clinical and Laboratory Features.

Background: The discrimination of tuberculous meningitis and bacterial meningitis remains difficult at present, even with the introduction of advanced diagnostic tools. This study aims to differentiate these two kinds of meningitis by using the rule of clinical and laboratory features. Methods: A prospective observational study was conducted to collect the clinical and laboratory parameters of patients with tuberculous meningitis or bacterial meningitis. Logistic regression was used to define the diagnostic formula for the discrimination of tuberculous meningitis and bacterial meningitis. A receiver operator characteristic curve was established to determine the best cutoff point for the diagnostic formula. Results: Five parameters (duration of illness, coughing for two or more weeks, meningeal signs, blood sodium, and percentage of neutrophils in cerebrospinal fluid) were predictive of tuberculous meningitis. The diagnostic formula developed from these parameters was 98% sensitive and 82% specific, while these were 95% sensitive and 91% specific when prospectively applied to another 70 patients. Conclusion: The diagnostic formula developed in the present study can help physicians to differentiate tuberculous meningitis from bacterial meningitis in high-tuberculosis-incidence-areas, particularly in settings with limited microbiological and radiological resources.

The cost of Alzheimer's disease in China and re-estimation of costs worldwide.

INTRODUCTION: The socioeconomic costs of Alzheimer's disease (AD) in China and its impact on global economic burden remain uncertain. METHODS: We collected data from 3098 patients with AD in 81 representative centers across China and estimated AD costs for individual patient and total patients in China in 2015. Based on this data, we re-estimated the worldwide costs of AD. RESULTS: The annual socioeconomic cost per patient was US $19,144.36, and total costs were US $167.74 billion in 2015. The annual total costs are predicted to reach US $507.49 billion in 2030 and US $1.89 trillion in 2050. Based on our results, the global estimates of costs for dementia were US $957.56 billion in 2015, and will be US $2.54 trillion in 2030, and US $9.12 trillion in 2050, much more than the predictions by the World Alzheimer Report 2015. DISCUSSION: China bears a heavy burden of AD costs, which greatly change the estimates of AD cost worldwide.

Evaluation of interferon-gamma release assays in extrasanguinous body fluids for diagnosing tuberculosis: A systematic review and meta-analysis.

AIMS: In this study, we conducted a meta-analysis to systematically compare the diagnostic accuracy of IGRAs performed for extrasanguinous body fluids with that performed for blood in the diagnosis of TB. MAIN METHODS: Multiple English and Chinese databases were searched up to November 2017. Studies that complied with the guidelines for the Quality Assessment of Diagnostic Accuracy Studies and used QuantiFERON-TB Gold In-Tube and/or T-SPOT.TB (ELISPOT) assays on both blood and extrasanguinous body fluids were included. Statistical analysis was performed using Stata 12.0 software. Since publication bias is a concern in the meta-analysis of diagnostic studies, we tested for this using Begg's funnel plots. KEY FINDING: Among the 1332 articles searched from the databases, 24 articles met the inclusion criteria, which included 1040 samples in the patient group and 1044 samples in the control group. For extrasanguinous body fluids, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) area under the curve (AUC) were 87% (95% CI: 0.81-0.91), 89% (95% CI: 0.84-0.93), 8.22 (95% CI 5.38-12.56), 0.15 (95% CI: 0.10-0.21), 44.92 (95% CI: 25.61-78.81), and 0.94 (95% CI: 0.92-0.96), respectively. For peripheral blood, these values were 83% (95% CI: 0.79-0.87), 74% (95% CI: 0.68-0.79), 3.17 (95% CI 2.63-3.84), 0.23 (95% CI: 0.19-0.29), 12.99 (95% CI: 10.19-16.57), and 0.86 (95% CI: 0.82-0.89), respectively. SIGNIFICANCE: IGRAs performed on extrasanguinous body fluids exhibited a better diagnostic accuracy compared with IGRAs performed on peripheral blood for diagnosing TB.

Inflammatory response and neuronal necrosis in rats with cerebral ischemia.

In the middle cerebral artery occlusion model of ischemic injury, inflammation primarily occurs in the infarct and peripheral zones. In the ischemic zone, neurons undergo necrosis and apoptosis, and a large number of reactive microglia are present. In the present study, we investigated the pathological changes in a rat model of middle cerebral artery occlusion. Neuronal necrosis appeared 12 hours after middle cerebral artery occlusion, and the peak of neuronal apoptosis appeared 4 to 6 days after middle cerebral artery occlusion. Inflammatory cytokines and microglia play a role in damage and repair after middle cerebral artery occlusion. Serum intercellular cell adhesion molecule-1 levels were positively correlated with the permeability of the blood-brain barrier. These findings indicate that intercellular cell adhesion molecule-1 may be involved in blood-brain barrier injury, microglial activation, and neuronal apoptosis. Inhibiting blood-brain barrier leakage may alleviate neuronal injury following ischemia.

Association of susceptibility to multiple sclerosis in Southern Han Chinese with HLA-DRB1, -DPB1 alleles and DRB1-DPB1 haplotypes: distinct from other populations.

Association of HLA class II with multiple sclerosis (MS) has been widely studied in both Western and Oriental populations. However, such an association is not well documented in Chinese. The objective of this study was to examine the association between the susceptibility to conventional MS in Southern Chinese with HLA-DRB1,-DPB1 alleles and putative DRB1-DPB1 haplotypes. Genotyping of HLA-DRB1 and -DPB1 alleles was performed in 60 patients with conventional MS and 95 controls. Allele frequencies were compared between patients and controls to identify MS-associated alleles. Relative predisposing effect method was used to compare haplotype frequencies in patients and controls and to identify possible predisposing DRB1-DPB1 haplotypes, which were further examined for differences in haplotype carriage rates between the two groups. We found that the allele frequency of DRB1*1501 was not different between patients (18.3%) and controls (21.1%) (p = 0.837). In contrast, frequency of the DPB1*0501 allele was significantly higher in patients (90%) than in controls (67.4%) (odds ratio = 4.36, p = 0.0013, pcorr = 0.025). DRB1-DPB1 linkage haplotype in patients (8.33%) was significantly higher than in controls (0%) (p < 0.0001) and the carriage rate of this haplotype was significantly increased in patients (15%) as compared with controls (0%) (p = 0.00013, pcorr = 0.003). Combined, these results suggest that HLA-DRB1*1501 is not associated with susceptibility to conventional MS in Southern Chinese. Instead, both the DPB1*0501 allele and the DRB1*1602- DPB1*0501 haplotype are strong predisposing factors for conventional MS in this population. Our results establish that the HLA profiles of MS in Southern Chinese are distinct from other populations.

Balo's disease showing benign clinical course and co-existence with multiple sclerosis-like lesions in Chinese.

Baló's concentric sclerosis (BCS) is a rare demyelinating disorder usually considered a variant of multiple sclerosis (MS). However, its pathogenesis and its correlation with MS remains unclear and controversial. This report presents seven Hans Chinese subjects diagnosed as BCS on the basis of the pathognomonic MR (magnetic resonance) findings. Upon diagnosis, all the cases displayed good responses to corticosteroids and showed an overall benign prognosis during a follow-up period of 4-13.5 years, although three relapsed later. MR findings suggest that the characteristic concentric lesions of BCS frequently (5/7) coexist with multiple sclerosis-like lesions. During follow-up, the Baló-like lesions may either dissolve over time or transform into an MS-like lesion. Moreover, the Balóand MS-like lesions occurred one after another at the onset and relapse phases of the same patient in two cases. These clinical features suggest that Baló's disease showing benign clinical course and co-existence of multiple sclerosis (MS)-like lesion is not rare among the Chinese, and strengthens the notion that BCS correlates intrinsically with MS.

[Association of HLA-DRB1 and -DPB1 allele polymorphism with multiple sclerosis in Chinese Han population from Southern areas].

OBJECTIVE: To examine the correlation between multiple sclerosis (MS) in Chinese Southern Han population and the polymorphism of HLA-DRB1 and -DPB1 alleles, and compare it to the reports of Western, Japanese and Northern Chinese populations. METHODS: The HLA-DRB1 and -DPB1 alleles of 26 patients with conventional MS (C-MS), 13 patients with optic-spinal form of MS (OS-MS), and 50 normal controls were determined by sequence-based typing (SBT) method. The frequency of the HLA alleles was compared between the 2 MS subtypes and the MS subtypes and the controls by chi(2) or Fisher exact probability test. The P values were corrected according to Bonferroni's method to calculate corrected the P values (Pc). RESULTS: A total of 27 HLA-DRB1 alleles and 13 HLA-DPB1 alleles were identified in the 39 MS patients and 50 controls. The frequencies of DRB1(*)0406 (P = 0.014, OR = 2.09) and DRB1(*)1302 alleles (P = 0.007, OR = 2.84) were higher in the OS-MS patients than in the controls. In addition, the DRB1(*)120201 allele was more frequent in the C-MS patients than in the controls, and the frequency of DPB1(*)2101 was higher in the OS-MS patients than in the controls. However, all the differences were of no significance since the corrected P values (Pc) were all > 0.1. There was no correlation between the MS subtypes and the HLA-DRB1(*)1501 or DPB1(*)0501 as reported in Western and Japanese populations (all P > 0.1). CONCLUSION: The correlation between HLA-DRB1 and -DPB1 in Southern Han MS population is different from that in the Western, Japanese, and Northern Chinese populations. Southern Han MS patients may be linked to the HLA-DRB1(*)0406, DRB1(*)1302, DRB1(*)120201 and DPB1(*)2101, but not to the HLA-DRB1(*)1501 or DPB1(*)0501 alleles as reported in the above populations.

Th1 shift in CIDP versus Th2 shift in vasculitic neuropathy in CSF.

To investigate the intra- and extracellular levels of various cytokines and chemokines in CSF in chronic inflammatory demyelinating polyneuropathy (CIDP) and vasculitic neuropathy (VN), 16 cytokines, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, IFN-gamma, TNF-alpha, G-CSF, MCP-1 and MIP-1beta, were measured in CSF supernatant by a multiplexed fluorescent bead-based immunoassay and intracellular production of IFN-gamma and IL-4 in CSF CD4+ T cells were simultaneously measured by flow cytometry in 14 patients with CIDP, 8 patients with VN and 25 patients with other noninflammatory neurologic diseases (OND). In the CSF supernatant, a significant increase of IL-17, IL-8 and IL-6, and a significant decrease of IL-4, IL-5 and IL-7 levels were detected in pretreated CIDP as compared with OND. A significant increase of IL-6, IL-8 and IL-10 levels was found in pretreated VN. Both IL-17 and IL-8 levels correlated strongly with CSF protein levels in CIDP, although the correlation of IL-6 levels was weak. In CSF CD4+ T cells, IFN-gamma+ IL-4- cell percentages were markedly elevated in CIDP compared with OND, but not in VN, resulting in a significant increase of intracellular IFN-gamma/IL-4 ratio in CIDP, even in the absence of CSF pleocytosis. The nonresponders to intravenous immunoglobulins (IVIGs) showed a significantly lower IFN-gamma- IL-4+ CD4+ T cell percentage, and tended to have a higher intracellular IFN-gamma/IL-4 ratio than the responders in CSF. Marked upregulation of Th1 cytokine, IL-17, and downregulation of Th2 cytokines, together with infiltration of IFN-gamma-producing CD4+ T cells are useful markers for CIDP, while several Th2 cytokines are upregulated in VN in CSF.