Chengwei Chen

Cognitive impairment involves large‐scale brain systems, but the relation between white matter microstructure and default mode network (DMN) organization remains unclear in clinically heterogeneous populations. In this secondary analysis of Alzheimer's Disease Neuroimaging Initiative data, we examined structural abnormalities, DMN organization, and cognition. The structural analysis included 1431 classified participants with diffusion tensor imaging (DTI) data. After deduplication, the multimodal source merge yielded 1452 unique participant‐visits from 905 participants. Primary analyses used participant‐level random‐intercept models adjusted for scan age, sex, education, and diagnosis, alongside first‐available‐visit HC3‐robust sensitivity analyses. Global fractional anisotropy (FA), DMN within‐network connectivity, DMN segregation, and Mini‐Mental State Examination (MMSE) scores were lower in Alzheimer's disease than in cognitively normal participants. Global FA was positively associated with DMN within‐network connectivity in the primary model (standardized beta = 0.080, 95% confidence interval [] 0.022 to 0.137, p = 0.006; q = 0.019). The prespecified tract analysis identified FDR‐supported associations for splenial, callosal, and cingulate‐cingulum FA. The global association attenuated after scanner‐platform adjustment (beta = 0.052, 95% CI −0.007 to 0.112, p = 0.082), quantifying an important multicenter limitation. DMN within‐network connectivity was not independently associated with MMSE in the primary mixed model (beta = 0.035, 95% CI −0.003 to 0.073, p = 0.071). In a same‐visit amyloid/tau subset (216 observations, 180 participants), diagnosis‐adjusted analyses showed no non‐monotonic imaging pattern. In this audited multimodal cohort, we identified diagnosis‐related group differences and a positive participant‐level structure–function association between white matter integrity and DMN organization, underscored by anatomically heterogeneous tract‐level effects. Acknowledging cross‐sectional and scanner‐variance constraints, these findings provide a hypothesis‐generating basis for future investigations into coupled structural‐functional network disruptions across the Alzheimer's continuum.

Vascular dementia (VaD), caused by reduced cerebral blood flow, is a common form of dementia lacking effective treatments. This study used genome‐wide association study (GWAS) summary data, Mendelian randomization (MR), and colocalization analyzes to prioritize blood metabolites and candidate therapeutic targets associated with VaD. Key analyzes included metabolic pathway enrichment, a descriptive Phenome‐Wide Association Study (PheWAS) of the broader curated association profiles of prioritized genes, mediation analysis, and in‐silico compound prioritization with molecular docking. Twenty‐four metabolites were associated with VaD, with taurocholate and glutaroyl carnitine prioritized as tier 1 metabolite–gene pairs. Pathway analysis implicated aminoacyl‐tRNA and branched‐chain amino acid biosynthesis pathways. Apolipoprotein E (APOE) and glutaryl‐CoA dehydrogenase (GCDH) were prioritized candidate genes. The PheWAS recapitulated APOE's curated associations with Alzheimer's disease and lipid traits, whereas GCDH had a more restricted curated association profile dominated by glutaric acidemia type I; these patterns provide pleiotropic context but do not establish safety. Single‐cell RNA‐sequencing analysis localized APOE predominantly to microglia and astrocytes and GCDH predominantly to oligodendrocytes, providing cell‐type‐specific context. Mediation analysis identified a statistically supported indirect pathway involving alpha‐2‐macroglobulin receptor‐associated protein for taurocholate. Aflatoxin B1 was highly ranked in an in‐silico query but, because of its established toxicity, is not a therapeutic candidate. This study prioritizes metabolic and genetic candidates for experimental and clinical follow‐up rather than establishing therapeutic targets.

Near‐infrared photobiomodulation has been identified as a potential strategy for Alzheimer's disease (AD). However, the mechanisms underlying this therapeutic effect remain poorly characterize. Herein, it is illustrate that 1070‐nm light induces the morphological alteration of microglia from an M1 to M2 phenotype that secretes exosomes, which alleviates the β‐amyloid burden to improve cognitive function by ameliorating neuroinflammation and promoting neuronal dendritic spine plasticity. The results show that 4 J cm⁻² 1070‐nm light at a 10‐Hz frequency prompts microglia with an M1 inflammatory type to switch to an M2 anti‐inflammatory type. This induces secretion of M2 microglial‐derived exosomes containing miR‐7670‐3p, which targets activating transcription factor 6 (ATF6) during endoplasmic reticulum (ER) stress. Moreover, it is found that miR‐7670‐3p reduces ATF6 expression to further ameliorate ER stress, thus attenuating the inflammatory response and protecting dendritic spine integrity of neurons in the cortex and hippocampus of 5xFAD mice, ultimately leading to improvements in cognitive function. This study highlights the critical role of exosomes derive from 1070‐nm light‐modulated microglia in treating AD mice, which may provide a theoretical basis for the treatment of AD with the use of near‐infrared photobiomodulation.

The present study reports the effect of successful treatment of cerebral venous sinus thrombosis (CVST) with stent retriever thrombectomy combined with local thrombolytic therapy. Medical records of 29 patients were retrospectively analyzed following a diagnosis of CVST with magnetic resonance venography (MRV) or digital subtraction angiography (DSA). Systemic anticoagulation was the initial treatment in all patients following admission. In group A, stent retriever thrombectomy combined with local thrombolytic therapy was performed on 14 patients who met the criteria of endovascular therapy. Stent‑assisted angioplasty was also performed when patients presented with venous sinus stenosis. A total of 15 patients in group B received systemic anticoagulant treatment. Subsequently, warfarin was administered orally for 3 to 12 months as a continuous anticoagulant therapy. International normalized ratio was monitored when patients were receiving anticoagulant therapy. Additionally, clinical presentation, decision to escalate therapy, recanalization, Glasgow Coma Scale, modified Rankin Scale (mRS) and the clinical outcome was assessed. A total of 14 patients (9 female patients, 5 male patients), with ages ranging from 17 to 57 years, met the criteria of endovascular therapy. The clinical symptoms of 12 patients had improved after receiving endovascular therapy and only 2 patients suffered from intracranial hemorrhage following the procedure. Complete recanalization of venous sinus was exhibited in 10/14 (71.4%) patients in group A when compared with 1/15 (6.7%) patients in group B. mRS were improved in the 12‑month follow‑up in groups A and B when compared with that at admission. In the present study, patients with acute CVST treated with stent retriever thrombectomy combined with local thrombolytic therapy had a favorable outcome. To conclude, the present study provides a treatment option in treating CVST, particularly for patients that present with evident cortical venous outflow stasis or deteriorate neurology, despite appropriate anticoagulant therapy.