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BACKGROUND. Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) plays an important role in the clearance of pathological amyloid-[beta] (A[beta]) in Alzheimer's disease (AD). This study aimed to explore sTREM2 as a central and peripheral predictor of the conversion from mild cognitive impairment (MCI) to AD. METHODS. sTREM2 and A[[beta].sub.1-42] levels in cerebrospinal fluid (CSF) and florbetapir-PET (AV45) images were analyzed for healthy control (HCs), patients with MCI, and patients with AD from the ADNI database. Peripheral plasma sTREM2 and A[[beta].sub.1-42] levels were determined for our Neurology database of Ruijin Hospital for Alzheimer's Disease (NRHAD) cohort, and patients with MCI were reevaluated at follow-up visits to assess for progression to AD. The association between CSF and plasma sTREM2 levels was analyzed in data from the Chinese Alzheimer's Biomarker and Lifestyle (CABLE) database. RESULTS. The results showed that patients with MCI who had low levels of CSF sTREM2 and A[[beta].sub.1-42] were more likely to develop AD. Among participants with positive A[beta] deposition, as assessed by AV45 imaging, elevated CSF sTREM2 levels were associated with a decreased risk of MCI-to-AD conversion. Meanwhile, in the NRHAD cohort, individuals in the MCI group with high sTREM2 levels in plasma were at a greater risk for AD, whereas low A[[beta].sub.1-42] with high sTREM2 levels in plasma were associated with a faster cognitive decline. In addition, CSF sTREM2 levels were highly correlated with plasma sTREM2 levels in the CABLE database. CONCLUSION. These findings suggest that sTREM2 may be useful as a potential predictive biomarker of MCI-to-AD conversion. FUNDING. This study was supported by grants from the National Natural Science Foundation of China (grant nos. 82001341, 82071415, 81873778, and 82201392); the Shanghai Sailing Program (grant no. 22YF1425100); and the China Postdoctoral Science Foundation funded project (grant no. 2021M702169)., Introduction Triggering receptor expressed on myeloid cells 2 (TREM2), a transmembrane receptor expressed in myeloid cells, plays an important role in regulating microglial phagocytosis and the response to inflammatory stimuli [...]

INTRODUCTION: We investigated the association between white matter hyperintensities (WMH) and regional cortical thickness, amyloid and tau deposition, and synaptic density in the WMH‐connected cortex using multimodal images. METHODS: We included 107 participants (59 with Alzheimer's disease [AD]; 27 with mild cognitive impairment; 21 cognitively normal controls) with amyloid beta (Aβ) positivity on amyloid positron emission tomography (PET). The cortex connected to WMH was identified using probabilistic tractography. RESULTS: We found that WMH connected to the cortex with more severe regional degeneration as measured by cortical thickness, Aβ and tau deposition, and synaptic vesicle glycoprotein 2 A (SV2A) density using 18F‐SynVesT‐1 PET. In addition, higher ratios of Aβ in the deep WMH‐connected versus WMH‐unconnected cortex were significantly related to lower cognitive scores. Last, the cortical thickness of WMH‐connected cortex reduced more than WMH‐unconnected cortex over 12 months. DISCUSSION: Our results suggest that WMH may be associated with AD‐intrinsic processes of degeneration, in addition to vascular mechanisms. Highlights: We studied white matter hyperintensities (WMHs) and WMH‐connected cortical changes.WMHs are associated with more severe regional cortical degeneration.Findings suggest WMHs may be associated with Alzheimer's disease–intrinsic processes of degeneration. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We aimed to investigate the effect of apolipoprotein E4 (APOE) ε4 on synaptic density in cognitively impaired (CI) participants. METHODS: One hundred ten CI participants underwent amyloid positron emission tomography (PET) with 18F‐florbetapir and synaptic density PET with 18F‐SynVesT‐1. We evaluated the influence of APOE ε4 allele on synaptic density and investigated the effects of ε4 genotype on the associations of synaptic density with Alzheimer's disease (AD) biomarkers. The mediation effects of AD biomarkers on ε4‐associated synaptic density loss were analyzed. RESULTS: Compared with non‐carriers, APOE ε4 allele carriers exhibited significant synaptic loss in the medial temporal lobe. Amyloid beta (Aβ) and tau pathology mediated the effects of APOE ε4 on synaptic density to different extents. The associations between synaptic density and tau pathology were regulated by the APOE ε4 genotype. DISCUSSION: The APOE ε4 allele was associated with decreased synaptic density in CI individuals and may be driven by AD biomarkers. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To prospectively evaluate the association between modifiable lifestyle factors and peripheral artery disease (PAD) among individuals with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We included 14,543 individuals with T2D from the UK Biobank. We defined a weighted healthy lifestyle score using nonsmoking, regular physical activity, high-quality diet, moderate alcohol consumption, optimal waist-to-hip ratio, and adequate sleep duration, and categorized into unfavorable, intermediate, and favorable lifestyles. We created a genetic risk score (GRS) using 19 single nucleotide polymorphisms previously found to be associated with PAD. We modeled the association between lifestyle score and PAD, overall and stratified by PAD genetic susceptibility. RESULTS: After a median 13.5 years of follow-up, 628 incident cases of PAD were documented. A linear inverse association between the weighted lifestyle score and PAD was observed, with a hazard ratio (HR) (95% CI) of 0.27 (0.19, 0.38) for favorable compared with unfavorable lifestyle (Ptrend < 0.0001). An estimated 58.3% (45.0%, 69.1%) of PAD in this population could be potentially avoidable if all participants attained a favorable lifestyle. Moreover, the PAD GRS was associated with increased PAD risk (HR [95% CI] per SD increment: 1.13 [1.03, 1.23]). A favorable lifestyle was able to partially mitigate the excess risk of PAD associated with higher GRS, albeit as a nonsignificant interaction. Several biomarkers in the lipid metabolism, hepatic/renal function, and systemic inflammation pathways collectively explained 13.3% (8.5%, 20.1%) of the association between weighted lifestyle score and PAD. CONCLUSIONS: A favorable lifestyle was associated with lower risk of PAD among individuals with T2D, independent of genetic predisposition to PAD. [ABSTRACT FROM AUTHOR]

Based on the excellent comprehensive mechanical properties of high–entropy alloy (HEA), the NiAl-based HEA was designed to achieve excellent high-temperature strength, toughness, and wear resistance. In this work, vacuum arc melting technology was used to prepare (NiA1)78(CoCrFe)16.5Cu5.5 HEA, and its microstructure, phase composition, and mechanical properties were systematically studied. The results showed that (NiA1)78(CoCrFe)16.5Cu5.5 HEA was composed of FCC and BCC/B2, with a spinodal decomposition structure in the matrix, and nano-precipitation in the interdendritic, exhibiting a good high-temperature performance. At 600 °C, the compressive fracture strength is 842.5 MPa and the fracture strain is 24.5%. When the temperature reaches 800 °C, even if the strain reaches 50%, the alloy will not fracture, and the stress–strain curve shows typical work hardening and softening characteristics. The wear coefficient of the alloy first increases and then decreases with the increase in temperature in the range of room temperature to 400 °C. However, the specific wear rate shows the opposite trend. At 100 °C, the wear rate reaches the lowest of 7.05 × 10−5 mm3/Nm, and the wear mechanism is mainly abrasive wear. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to clarify the association of the 21 single nucleotide polymorphisms (SNPs) with Alzheimer's disease (AD) in the population of southern China. Methods: A case-control study was conducted with a total sample size of 490 subjects (246 patients with AD and 244 age- and gender-matched healthy controls) enrolled in this study. Twenty-one selected SNPs were detected using SNaPshot assay and polymerase chain reaction (PCR) technique. Then, we assessed how these SNPs correlated with AD susceptibility. Results: The results showed that rs3764650 of ABCA7 was closely correlated with risen AD morbidity in the allele [ P = 0.010, odds ratio (OR) = 1.43, 95% confidence interval (CI) 1.09–1.89], dominant (P = 0.004, OR = 1.71, 95% CI 1.19–2.46), and additive (P = 0.012, OR = 1.42, 95% CI 1.08–1.86) models. However, rs4147929 of ABCA7 was related to higher AD risk in the allele (P = 0.006, OR = 1.45, 95% CI 1.11–1.89), dominant (P = 0.012, OR = 1.59, 95% CI 1.11–2.27), and additive (P = 0.010, OR = 1.40, 95% CI 1.08–1.81) models. In addition, the frequencies of the G-allele at rs3764650 (P = 0.030) and the A-allele at rs4147929 (P = 0.001) in AD were statistically higher in APOE ε4 carriers in comparison to non-carriers. Conclusion: This study demonstrated that the G-allele at rs3764650 and the A-allele at rs4147929 appeared at higher risk for developing AD, particularly in APOE ε4 carriers. Moreover, it was observed that rs3764650 and rs4147929 of ABCA7 were linked to AD. More in-depth research with a relatively large sample is needed to make the results more convincing. [ABSTRACT FROM AUTHOR]

Background and Objective: Alzheimer's disease (AD) has been shown to affect vision in human patients and animal models. This study was conducted to explore ocular abnormalities in the primary visual pathway and their relationship with hippocampal atrophy in patients with AD and mild cognitive impairment (MCI). The aim of this study was to investigate the potential value of ocular examinations as a biomarker during the AD progression. Methods: Patients with MCI (n = 23) or AD (n = 17) and age-matched cognitively normal controls (NC; n = 19) were enrolled. Pattern visual-evoked potentials (PVEP), flash electroretinogram (FERG) recordings and optical coherence tomography (OCT) were performed for all participants. Hippocampal volumes were measured by 3T magnetic resonance imaging. Cognitive function was assessed by Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). Pearson correlation was employed to analyze the potential associations between ocular abnormalities and hippocampal volumes. Hierarchical regression models were conducted to determine associations between cognitive performances and ocular abnormalities as well as hippocampal volumes after adjusting for confounding factors including age, sex, cognitive reserve, and APOE4 status. Results: PVEP amplitude of P100 waveform was significantly decreased in AD patients compared to MCI and normal individuals. In FERG test, delayed latencies of rod response, rod cone response and 3.0 flicker time were found in cognitively impaired groups, indicating dysfunctions of both the rod and cone systems in the disease progression. OCT test revealed reduced macular retinal nerve fiber layer (m-RNFL) thickness in MCI and AD patients, which significantly correlated with brain structure of hippocampus particularly vulnerable during the progression of AD. Interestingly, P100 amplitude showed a significant association with hippocampal volumes even after adjusting confounding factors including age, sex, and cognitive reserve. Hierarchical regression analysis further demonstrated that m-RNFL thickness, as well as hippocampal volumes, significantly associated with ADAS-cog scores. Conclusion: P100 amplitude and m-RNFL thickness showed significant correlations with brain structure involved in AD-related neurodegeneration, and therefore proved to be potential indicators of brain imaging pathologies. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to explore the relationship between 18 single nucleotide polymorphisms (SNPs) and Alzheimer's disease (AD) within the southern Chinese population. Methods: A total of 420 participants, consisting of 215 AD patients and 205 sex- and age-matched controls, were recruited. The SNaPshot technique and polymer chain reaction (PCR) were used to detect the 18 SNPs. Combined with the apolipoprotein E (APOE) ε4 allele and age at onset, we performed an association analysis between these SNPs and AD susceptibility. Furthermore, we analyzed SNP-associated gene expression using the expression quantitative trait loci analysis. Results: Our study found that rs17125924 of FERMT2 was associated with the risk of developing AD in the dominant (P = 0.022, odds ratio [OR] = 1.57, 95% confidence interval [CI]: 1.07–2.32) and overdominant (P = 0.005, OR = 1.76, 95% CI: 1.18–2.61) models. Moreover, compared with APOE ε4 non-carriers, the frequency of the G-allele at rs17125924 was significantly higher among AD patients in APOE ε4 allele carriers (P = 0.029). The rs9271058 of HLA-DRB1 (dominant, overdominant, and additive models), rs9473117 of CD2AP (dominant and additive models), and rs73223431 of PTK2B (dominant, overdominant, and additive models) were associated with early onset AD (EOAD). Using the genotype-tissue expression (GTEx) and Braineac database, we found a significant association between rs9271058 genotypes and HLA-DRB1 expression levels, while the CC genotype at rs9473117 and the TT genotype of rs73223431 increased CD2AP and PTK2B gene expression, respectively. Conclusion: Our study identifies the G-allele at rs17125924 as a risk factor for developing AD, especially in APOE ε4 carriers. In addition, we found that rs9271058 of HLA-DRB1 , rs9473117 of CD2AP , and rs73223431 of PTK2B were associated with EOAD. Further studies with larger sample sizes are needed to confirm our results. [ABSTRACT FROM AUTHOR]

Objective: It is challenging for neurosurgeons to perform surgeries on patients without detectable structural lesions. Therefore, this retrospective study aimed to explore the outcome of stereo-electroencephalography (SEEG) in suspicious areas guided by magnetoencephalography (MEG)-magnetic resonance imaging (MRI) reconstruction in MRI-negative epilepsy patients. Methods: This study included 47 patients with negative-MRI epilepsy. Seizure outcome at 24 months was assessed using a modified Engel's classification. Accordingly, class I and II were considered favorable outcomes, whereas classes III and IV were unfavorable. Furthermore, patients were classified into a consistent group if the results of MEG and SEEG indicated the same area of the brain. The relationship between surgical outcome and the concordance of MEG and SEEG was analyzed. Results: A complete seizure-free condition was achieved in 22 (47%) patients. Sex, handedness, age and duration of illness were not significantly associated with seizure-free outcome (p =.187 [Pearson chi-squared test]). The number of patients with favorable outcome (Engle I and II) was as high as 68% at the time of follow-up. Furthermore, more seizure-free patients were found in the SEEG and MEG consistent group. Conclusions: SEEG is a valuable tool in the pre-evaluation for resective epilepsy surgery, particularly in negative-MRI epilepsy patients; MEG greatly facilitates localization for SEEG electrode implantation. However, none of these tools are absolutely sensitive and reliable; therefore, collecting as much information as possible is necessary to achieve satisfactory results in epilepsy surgery. [ABSTRACT FROM AUTHOR]

A 62-years old Alzheimer's disease (AD) male patient donated his Peripheral blood mononuclear cells. The non-integrating episomal vector system used to reprogram PBMCs with Oct3/4, Klf4, Sox2 and c-Myc transcription factors. The pluripotency of transgene-free pluripotent stem cell (iPSC) was confirmed by immunocytochemistry for pluripotency markers-SOX2, NANOG, OCT3/4, SSEA4, TRA1-60, and TRA1-81. The differentiation capacity of the iPSCs into endoderm, mesoderm and ectoderm was assessed by AFP, SMA and βIII-TUBULIN, respectively. In addition, the iPSC line displayed a normal karyotype. This iPSC line might offer a good cell model to explore the pathological mechanisms and treatment strategies for AD. [ABSTRACT FROM AUTHOR]

The loss of synaptic structure and function has been linked to the cognitive impairment of Alzheimer's disease (AD). Dysregulation of the actin cytoskeleton, which plays a key role in regulating the integrity of synapses and the transport of synaptic proteins, has been suggested to contribute to the pathology of AD. In this study, we found that glutamate receptor surface expression and synaptic function in frontal cortical neurons were significant diminished in a familial AD (FAD) model, which was correlated with the reduction of phosphorylated cofilin, a key protein regulating the dynamics of actin filaments. Injecting a cofilin dephosphorylation inhibitory peptide to FAD mice led to the partial rescue of the surface expression of AMPA and NMDA receptor subunits, as well as the partial restoration of AMPAR- and NMDAR-mediated synaptic currents. Moreover, the impaired working memory and novel object recognition memory in FAD mice were partially ameliorated by injections of the cofilin dephosphorylation inhibitory peptide. These results suggest that targeting the cofilin-actin signaling holds promise to mitigate the physiological and behavioral abnormality in AD. [ABSTRACT FROM AUTHOR]

IPSCs have great potential value in cell replacement therapy, pathogenesis research, screening for new drugs, and treatment of clinical disease. An 82-year-old woman with mild cognitive impairment (MCI) and her unaffected child donated their peripheral blood mononuclear cells (PBMC). Their PBMCs were reprogrammed using human OKSM transcription factors (SOX2, OCT3/4, KLF4 and C-MYC) via a non-integrated complementary vector system. In the newly developed hiPSC series SIAISi019-A and SIAISi020-A, immunocytochemistry and the ability to spontaneously differentiate into 3 germ layers in vitro confirmed the pluripotency of transgene-free iPSCs. And their karyotypes were normal. [ABSTRACT FROM AUTHOR]

A 71-year-old Han male from China contributed peripheral blood mononuclear cells (PBMCs). Non-integrative Sendai viral vectors containing reprogramming factors OCT4, KLF4, SOX2 and C-MYC were used to reprogram PBMCs. Pluripotency makers confirmed the pluripotency of transgene-free induced pluripotent stem cell (iPSC). The ability of iPSC to spontaneously differentiate three germ layers in vitro confirmed the pluripotency of iPSC. The iPSC line displayed a normal karyotype. The newly generated human iPSC SIAISi021-A can be used for studying further disease mechanisms of Alzheimer's Disease (AD). [ABSTRACT FROM AUTHOR]

The variations of SORCS1 gene may play potential key roles in late-onset Alzheimer’s disease (LOAD). To evaluate the relationship between the polymorphism of SORCS1 gene and LOAD in the ethnic Han Chinese, we conducted a case–control study to investigate the association between the single-nucleotide polymorphisms (SNPs) in intron 1 of SORCS1 and LOAD in Chinese Han population. Six reported SNPs in intron 1 of SORCS1 were analyzed by Snapshot, genotyping and haplotyping in 236 Chinese LOAD cases and 233 matched controls. The significant differences in frequencies of two SNPs (rs10884402, rs950809) were found between the two groups. In addition, haplotype analyses revealed that, in the LOAD group, the frequency of haplotypes C-C-G-T-C (alleles in order of rs17277986, rs6584777, rs10884402, rs7078098, rs950809 polymorphisms) were significantly higher (Psim<0.0001) while haplotype C-C-A-T-C, C-C-A-C-C, T-T-A-C-C were significantly lower (Psim<0.0001). Our data suggested that the genetic variation of the rs10884402 and rs950809 in intron 1 of SORCS1 was associated with the late-onset AD in the Chinese Han population. [ABSTRACT FROM AUTHOR]

Objective: We conducted a case-control study to investigate whether TREM2 polymorphism (rs75932628-T) was associated with late onset Alzheimer's disease in Chinese Southern Han population. Methods: PCR-restriction fragment length polymorphism assay was performed to genotype rs75932628 in 279 cases with late onset Alzheimer's diseases patients and 346 control subjects in Shanghai and Nanjing. Results: There was no rs75932628-T variant detected in our sample. However, APOE&4 was shown closely associated with the risk of Alzheimer's disease (Chi-square=60.288, P= 0.000). Conclusion: Our study suggested that TREM2(rs75932628-T) was rare in Chinese Han population. Further association studies with large samples are needed to further study the association of TREM2 with late-onset Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Induced pluripotent stem cells play vitally essential roles in regenerative medicines for disease modeling and drug screening. Here, we successfully generated an iPSC line from PBMC of a 60-year-old female with mild cognitive impairment in an APOE 4/4 background to better understand studies relating to MCI and other cognitive diseases. In the newly-developed hiPSC line SIAISi009-A, all pluripotent markers were well expressed. Moreover, cells displayed a normal karyotype and have differentiation potential proven by in vitro trilineage differentiation method. [ABSTRACT FROM AUTHOR]

A 66-year-old Chinese Han Alzheimer's Disease (AD) female patient and her two unaffected children donated their Peripheral blood mononuclear cells (PBMC). Non-integrating episomal vector system were used to reprogram their PBMCs with human OKSM (OCT3/4, KLF4, SOX2, and c-MYC) transcription factors. Immunocytochemistry for pluripotency makers confirmed the pluripotency of transgene-free iPSCs. Pluripotency was confirmed by the ability of iPSCs to spontaneously differentiate three germ layers in vitro as well. The iPSC line displayed a normal karyotype. This model provides insight into further pathological studies to research identify early biomarkers, study disease pedigrees, and also for drug testing purposes. [ABSTRACT FROM AUTHOR]

A 39-year old healthy female with a family history of Alzheimer's disease (AD) and two copies of apolipoprotein E(APOE) ε4 allele donated her Peripheral blood mononuclear cells (PBMC). The non-integrative Sendai viral vectors used to reprogram PBMCs with the human OKSM transcription factors. The pluripotency of iPSCs was confirmed by immunocytochemistry and ability of differentiation spontaneously into 3 germ layers. Furthermore, the iPSC line displayed a normal karyotype. The APOE gene is currently considered to be the most relevant gene for sporadic AD. Our model might offer a platform to study the pathological mechanisms and drug testing studies in AD. [ABSTRACT FROM AUTHOR]

A 66-year old mild cognitive impairment (MCI) female patient donated her Peripheral blood mononuclear cells (PBMC). PBMC was reprogrammed using non-integrative Sendai viral vectors containing reprogramming factors OCT4, KLF4, SOX2 and C-MYC. The pluripotency of transgene-free iPSCs was confirmed by immunocytochemistry and ability of differentiation spontaneously into 3 germ layers in vitro. Moreover, the iPSC line displayed a normal karyotype. The apolipoprotein E (APOE) ε4 allele, is considered to be the strongest genetic risk factor for Sporadic Alzheimer's disease (AD). Our model might offer a good platform to study the pathological mechanisms and drug testing studies in AD and MCI. [ABSTRACT FROM AUTHOR]

• higher CSF levels of TNF-α related inflammatory proteins in the MCI and AD patients with positive tau pathology. • TNF receptors were associated with t-tau and p-tau, other than Aβ 1-42 , in HC, MCI and AD subjects. • TNF receptors are potential early predictors for the MCI-to-AD conversion. Tumor necrosis factor-a (TNF-α) signaling pathway plays a significant role in Alzheimer's disease (AD). This study aimed to explore the relationship between TNF-α related inflammatory proteins and pathological markers of AD, and examine their possibility as a predictor of the conversion of mild cognitive impairment (MCI) to AD. This study included both cross-sectional and longitudinal designs. The levels of TNF-α related inflammatory proteins, Aβ 1-42 , total-tau(t-tau), phosphorylated tau (p-tau) from cerebrospinal fluid (CSF) were analyzed in healthy controls (HC, n = 90), MCI (n = 116), and AD participants (n = 75) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Kaplan-Meier analyses were used to evaluate the predictive value of the examined putative AD markers after follow-up visits. In the cross-sectional cohort, we observed higher CSF levels of TNF-α related inflammatory proteins in the MCI and AD patients with positive tau pathology. TNF receptors (TNFR) were more closely associated with t-tau and p-tau than Aβ 1-42 , in HC, MCI and AD subjects. In the longitudinal cohort with a mean follow-up of 30.2 months, MCI patients with high levels of CSF TNFR1 (p = 0.001) and low levels of TNFR2 (p < 0.001) were more likely to develop into AD. TNFR-signaling might be involved in the early pathogenesis of AD and TNF receptors may serve as potential predictive biomarkers for MCI. [ABSTRACT FROM AUTHOR]

Our aim was to determine the independent predictors of minimum clinically important difference (MCID) in quality of life (QOL) after selective amygdalohippocampectomy (SAH) among Chinese patients with refractory mesial temporal lobe epilepsy (MTLE). We conducted a prospective study and enrolled 50 consecutive patients with refractory MTLE who underwent SAH after their presurgical evaluations. The variables independently associated with MCID in the Quality of Life in Epilepsy Inventory-31 (QOLIE-31) overall score 1 year after SAH were analyzed by multiple binary logistic regression analysis. Significant improvements in the QOLIE-31 overall score and all subscale scores were observed after SAH (p < 0.001). Among 50 patients with refractory MTLE, 78% reached the criteria for MCID of QOL overall score after SAH. In the multiple binary logistic regression model, the presurgical independent predictors of significant improvement by MCID in QOL were absence of depression diagnosis (adjusted odds ratio [OR] = 8.391, 95% confidence interval [CI] = 1.240–56.776, p = 0.029) and good cognitive function (adjusted OR = 8.427, 95% CI = 1.115–63.670, p = 0.039); the postoperative independent predictor was seizure freedom (adjusted OR = 8.477, 95% CI = 1.195–60.122, p = 0.032). The sensitivity and specificity for significant improvement in the QOL were 97.4% and 45.5% respectively, with an overall model accuracy of 86.0%. Presurgical depression, cognitive function, and postsurgical seizure freedom are independent predictors for meaningful improvement in QOL after SAH among the Chinese patients with refractory MTLE. Preoperative evaluation of patients with refractory MTLE should consider the cognitive dysfunction and psychological disorders. • We applied the MCID concept to determine significant improvement in the QOL. • Significant improvement in the QOL is demonstrated one year after epilepsy surgery. • Depression and cognitive function are independent presurgical predictors for meaningful improvement in QOL. • Seizure freedom is an independent postsurgical predictor for meaningful improvement in QOL. • Neuropsychological evaluations should be routinely administered before epilepsy surgery. [ABSTRACT FROM AUTHOR]

Introduction: We investigated the association between white matter hyperintensities (WMH) and regional cortical thickness, amyloid and tau deposition, and synaptic density in the WMH-connected cortex using multimodal images., Methods: We included 107 participants (59 with Alzheimer's disease [AD]; 27 with mild cognitive impairment; 21 cognitively normal controls) with amyloid beta (Aβ) positivity on amyloid positron emission tomography (PET). The cortex connected to WMH was identified using probabilistic tractography., Results: We found that WMH connected to the cortex with more severe regional degeneration as measured by cortical thickness, Aβ and tau deposition, and synaptic vesicle glycoprotein 2 A (SV2A) density using 18 F-SynVesT-1 PET. In addition, higher ratios of Aβ in the deep WMH-connected versus WMH-unconnected cortex were significantly related to lower cognitive scores. Last, the cortical thickness of WMH-connected cortex reduced more than WMH-unconnected cortex over 12 months., Discussion: Our results suggest that WMH may be associated with AD-intrinsic processes of degeneration, in addition to vascular mechanisms., Highlights: We studied white matter hyperintensities (WMHs) and WMH-connected cortical changes. WMHs are associated with more severe regional cortical degeneration. Findings suggest WMHs may be associated with Alzheimer's disease-intrinsic processes of degeneration., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: We aimed to investigate the effect of apolipoprotein E4 (APOE) ε4 on synaptic density in cognitively impaired (CI) participants., Methods: One hundred ten CI participants underwent amyloid positron emission tomography (PET) with 18 F-florbetapir and synaptic density PET with 18 F-SynVesT-1. We evaluated the influence of APOE ε4 allele on synaptic density and investigated the effects of ε4 genotype on the associations of synaptic density with Alzheimer's disease (AD) biomarkers. The mediation effects of AD biomarkers on ε4-associated synaptic density loss were analyzed., Results: Compared with non-carriers, APOE ε4 allele carriers exhibited significant synaptic loss in the medial temporal lobe. Amyloid beta (Aβ) and tau pathology mediated the effects of APOE ε4 on synaptic density to different extents. The associations between synaptic density and tau pathology were regulated by the APOE ε4 genotype., Discussion: The APOE ε4 allele was associated with decreased synaptic density in CI individuals and may be driven by AD biomarkers., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Context: Few studies have examined the relationship between vitamin D and the risk of recurrent cardiovascular (CV) events in people with coronary heart disease (CHD)., Objective: This study aimed to investigate the associations of serum 25-hydroxyvitamin D (25(OH)D) concentration and the vitamin D receptor (VDR) polymorphisms with the risk of recurrent CV events in individuals with established CHD., Methods: A total of 22 571 participants with CHD were included from the UK Biobank. Recurrent CV events, including myocardial infarction (MI), heart failure (HF), stroke, and CV disease mortality, were identified from electronic health records. Cox proportional-hazard models were used to calculate hazard ratios (HRs) and 95% CIs., Results: The median (interquartile range) of serum 25(OH)D concentration was 44.8 nmol/L (range, 30.3-61.4 nmol/L), and 58.6% of participants had 25(OH)D below 50 nmol/L. During a median follow-up of 11.2 years, a total of 3998 recurrent CV events were documented. After multivariable adjustment, there was a nonlinear inverse relationship between serum 25(OH)D and recurrent CV events (P nonlinearity <.01), and the decreasing risk gradually leveled off at around 50 nmol/L. Compared with participants with serum 25(OH)D less than 25.0 nmol/L, the HRs (95% CIs) for participants with serum 25(OH)D of 50.0 to 74.9 nmol/L were 0.64 (0.58-0.71) for recurrent CV events, 0.78 (0.65-0.94) for MI, 0.66 (0.57-0.76) for HF, and 0.66 (0.52-0.84) for stroke. In addition, these associations were not modified by genetic variants in the VDR., Conclusion: In people with established CHD, higher serum 25(OH)D concentrations were nonlinearly associated with a lower risk of recurrent CV events, with a potential threshold around 50 nmol/L. These findings highlight the importance of maintaining adequate vitamin D status in the prevention of recurrent CV events among individuals with CHD., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Alzheimer's disease (AD) is a multi-gene inherited disease, and apolipoprotein E ( APOE ) ɛ4 is a strong risk factor. Other genetic factors are important but limited., Objective: This study aimed to investigate the relationship between 17 single-nucleotide polymorphisms (SNPs) and AD in the Southern Chinese populations., Methods: We recruited 242 AD patients and 208 controls. The SNaPshot technique was used to detect the SNPs., Results: Adjusted for sex and age, we found rs6572869 ( FERMT2 ), rs11604680 ( CELF1 ), and rs1317149 ( CELF1 ) were associated with AD risk in the dominant (rs6572869: p  = 0.022, OR = 1.55; rs11604680: p  = 0.007, OR = 1.68; rs1317149: p  = 0.033, OR = 1.50) and overdominant models (rs6572869: p  = 0.001, OR = 1.96; rs11604680: p  = 0.002, OR = 1.82; rs1317149: p  = 0.003, OR = 1.80). rs9898218 ( COPI ) was associated with AD risk in the overdominant model ( p  = 0.004, OR = 1.81). Further, rs2741342 ( CHRNA2 ) was associated with AD protection in the dominant ( p  = 0.002, OR = 0.5) and additive models ( p  = 0.002, OR = 0.64). Mutations in rs10742814 ( CELF1 ), rs11039280 ( CELF1 ), and rs3752242 ( ABCA7 ) contributed to AD protection. Among them, rs10742814 ( CELF1 ), rs3752242 ( ABCA7 ), and rs11039280 ( CELF1 ) were more significantly associated with AD carrying APOE ɛ4, whereas rs1317149 ( CELF1 ) showed an opposite trend. Interestingly, rs4147912 ( ABCA7 ) and rs2516049 ( HLA-DRB1 ) were identified to be relevant with AD carrying APOE ɛ4. Using expression quantitative trait locus analysis, we found polymorphisms in CELF1 (rs10742814 and rs11039280), ABCA7 (rs4147912), HLA-DRB1 (rs2516049), and ADGRF4 (rs1109581) correlated with their corresponding gene expression in the brain., Conclusions: We identified four risk and four protective SNPs associated with AD in the Southern Chinese population, with different correlations between APOE ɛ4 carriers and non-carriers. rs4147912 ( ABCA7 ) and rs2516049 ( HLA-DRB1 ) were associated with AD carrying APOE ɛ4., Competing Interests: The authors have no conflict of interest to report., (© 2023 – The authors. Published by IOS Press.)

Aims: To examine the association of a healthy sleep pattern with the risk of recurrent cardiovascular events among patients with coronary heart disease (CHD)., Methods and Results: This prospective cohort study included 21 193 individuals with CHD from the UK Biobank. A healthy sleep score was generated based on a combination of chronotype, sleep duration, insomnia, and excessive daytime sleepiness. Cox proportional hazards regression models were applied to estimate the associations between healthy sleep score and recurrent cardiovascular events. During a median of 11.1 years of follow up, we documented 3771 recurrent cardiovascular events, including 1634 heart failure cases and 704 stroke cases. After multivariable adjustment, including lifestyle factors, medical history, and CHD duration, sleep 7-8 h/day, never/rarely insomnia, and no frequent daytime sleepiness were each significantly associated with a 12-22% lower risk of heart failure. In addition, compared with participants who had a healthy sleep score of 0-1, the multivariable-adjusted HR (95% CI) for participants with a healthy sleep score of 4 was 0.86 (0.75, 0.99) for recurrent cardiovascular events, 0.71 (0.57, 0.89) for heart failure, and 0.72 (0.51, 1.03) for stroke., Conclusions: Adherence to a healthy sleep pattern was significantly associated with a lower risk of recurrent cardiovascular events among patients with CHD, especially for heart failure. These findings indicate that healthy sleep behaviours could be beneficial in the prevention of cardiovascular event recurrence., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The relationship between switching rate of multilayer functional network and cognitive ability in mild cognitive impairment (MCI) and Alzheimers' disease remains unclear., Methods: We followed up MCI patients for one year and analyzed the association of switching rates with cognitive decline. The iterative and ordinal Louvain algorithm tracked the switching of functional networks, while elastic network regression and Bayesian belief networks were used to test the relationship between network switching rate and cognitive performance cross-sectionally and longitudinally., Results: The switching rate of the default mode network positively correlated with better cognitive function, while that of salience and executive control network was negatively associated with memory and executive function. The lower default mode network (DMN) switching rate predicted MCI progression to dementia, while the lower sensorimotor network switching rate heralded in slower cognitive decline., Conclusions: The present study investigated the predictive effect of switching rate on cognitive performance, as well as MCI progression to dementia. The inverse effect from different functional networks may become useful for early diagnosis and revealing the mechanism of neural networks in cognitive decline., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Objective: Numerous electroencephalography (EEG) studies focus on the alteration of electrical activity in patients with Alzheimer's Disease (AD), but there are no consistent results especially regarding functional connectivity. We supposed that the weighted Phase Lag Index (w- PLI), as phase-based measures of functional connectivity, may be used as an auxiliary diagnostic method for AD., Methods: We enrolled 30 patients with AD, 30 patients with Mild Cognitive Impairment (MCI), and 30 Healthy Controls (HC). EEGs were recorded in all participants at baseline during relaxed wakefulness. Following EEG preprocessing, Power Spectral Density (PSD) and wPLI parameters were determined to further analyze whether they were correlated to cognitive scores., Results: In the patients with AD, the increased PSD in theta band was presented compared with MCI and HC groups, which was associated with disturbances of the directional, computational, and delayed memory capacity. Furthermore, the wPLI revealed a distinctly lower connection strength between frontal and distant areas in the delta band and a higher connection strength of the central and temporo-occipital region in the theta band for AD patients. Moreover,we found a significant negative correlation between theta functional connectivity and cognitive scores., Conclusion: Increased theta PSD and decreased delta wPLI may be one of the earliest changes in AD and associated with disease severity. The parameter wPLI is a novel measurement of phase synchronization and has potentials in understanding underlying functional connectivity and aiding in the diagnostics of AD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The loss of synaptic structure and function has been linked to the cognitive impairment of Alzheimer's disease (AD). Dysregulation of the actin cytoskeleton, which plays a key role in regulating the integrity of synapses and the transport of synaptic proteins, has been suggested to contribute to the pathology of AD. In this study, we found that glutamate receptor surface expression and synaptic function in frontal cortical neurons were significant diminished in a familial AD (FAD) model, which was correlated with the reduction of phosphorylated cofilin, a key protein regulating the dynamics of actin filaments. Injecting a cofilin dephosphorylation inhibitory peptide to FAD mice led to the partial rescue of the surface expression of AMPA and NMDA receptor subunits, as well as the partial restoration of AMPAR- and NMDAR-mediated synaptic currents. Moreover, the impaired working memory and novel object recognition memory in FAD mice were partially ameliorated by injections of the cofilin dephosphorylation inhibitory peptide. These results suggest that targeting the cofilin-actin signaling holds promise to mitigate the physiological and behavioral abnormality in AD.

The variations of SORCS1 gene may play potential key roles in late-onset Alzheimer's disease (LOAD). To evaluate the relationship between the polymorphism of SORCS1 gene and LOAD in the ethnic Han Chinese, we conducted a case-control study to investigate the association between the single-nucleotide polymorphisms (SNPs) in intron 1 of SORCS1 and LOAD in Chinese Han population. Six reported SNPs in intron 1 of SORCS1 were analyzed by Snapshot, genotyping and haplotyping in 236 Chinese LOAD cases and 233 matched controls. The significant differences in frequencies of two SNPs (rs10884402, rs950809) were found between the two groups. In addition, haplotype analyses revealed that, in the LOAD group, the frequency of haplotypes C-C-G-T-C (alleles in order of rs17277986, rs6584777, rs10884402, rs7078098, rs950809 polymorphisms) were significantly higher (Psim<0.0001) while haplotype C-C-A-T-C, C-C-A-C-C, T-T-A-C-C were significantly lower (Psim<0.0001). Our data suggested that the genetic variation of the rs10884402 and rs950809 in intron 1 of SORCS1 was associated with the late-onset AD in the Chinese Han population.