Background: Frailty is a state of cumulative degradation of physiological functions that leads to adverse outcomes such as disability or mortality. Currently, there is still little understanding of the prognosis of pre-stroke frailty status with acute cerebral infarction in the elderly.Objective: We investigated the association between pre-stroke frailty status, 28-day and 1-year survival outcomes, and functional recovery after acute cerebral infarction.Methods: Clinical data were collected from 314 patients with acute cerebral infarction aged 65–99 years. A total of 261 patients completed follow-up in the survival cohort analysis and 215 patients in the functional recovery cohort analysis. Pre-stroke frailty status was assessed using the FRAIL score, the prognosis was assessed using the modified Rankin Scale (mRS), and disease severity using the National Institutes of Health Stroke Scale (NIHSS).Results: Frailty was independently associated with 28-day mortality in the survival analysis cohort [hazard ratio (HR) = 4.30, 95% CI 1.35–13.67, p = 0.014]. However, frailty had no independent effect on 1-year mortality (HR = 1.47, 95% CI 0.78–2.79, p = 0.237), but it was independently associated with advanced age, the severity of cerebral infarction, and combined infection during hospitalization. Logistic regression analysis after adjusting for potential confounders in the functional recovery cohort revealed frailty, and the NIHSS score was significantly associated with post-stroke severe disability (mRS > 2) at 28 days [pre-frailty adjusted odds ratio (aOR): 8.86, 95% CI 3.07–25.58, p < 0.001; frailty aOR: 7.68, 95% CI 2.03–29.12, p = 0.002] or 1 year (pre-frailty aOR: 8.86, 95% CI 3.07–25.58, p < 0.001; frailty aOR: 7.68, 95% CI 2.03–29.12, p = 0.003).Conclusions: Pre-stroke frailty is an independent risk factor for 28-day mortality and 28-day or 1-year severe disability. Age, the NIHSS score, and co-infection are likewise independent risk factors for 1-year mortality.

The aim of this study was to analyze cortical thickness and gray matter volume (GMV) changes in white matter hyperintensities (WMH) which were associated brain regions and their association with mild behavioral impairment (MBI) by means of voxel- and surface-based morphology (VBM and SBM). A total of 60 patients underwent 3T MRI scan and MBI checklist (MBI-C) assessment and were divided into two groups: lower WMH (LWMH) and higher WMH (HWMH). After adjusting for confounding factors i.e. age, gender, education, and total intracranial volume, we found a GMV decrease in the left anterior insula (AIns), right middle frontal gyrus, right central operculum, right fusiform gyrus, left cerebellum exterior, and thalamus proper in the HWMH group based VBM, while in the HWMH group based SBM we found cortical thickness decrease in the left lingual, right posterior cingulate cortex (rPCC), right precentral, left superior frontal, right medial orbitofrontal gyrus, and left pars opercularis. The HWMH group had higher MBI-C scores. The GMV in the left AIns and thalamus proper and the thickness of rPCC negatively correlated with the MBI-C scores. The mediation analysis suggested that WMH may partially mediate MBI-C scores by reducing the GMV and cortical thickness of the mentioned brain regions. In WMH patients, the occurrence of MBI is associated with atrophy of gray matter and cortex. The occurrence of MBI may be partially mediated by WMH through gray matter and cortical atrophy. It provides a new insight into the relationship between WMH and dementia.

Emerging evidence suggests that senescent microglia play a role in β-amyloid (Aβ) pathology and neuroinflammation in Alzheimer’s disease (AD). Targeting senescent cells with naturally derived compounds exhibiting minimal cytotoxicity represents a promising therapeutic strategy. This study aimed to investigate whether delphinidin, a naturally occurring anthocyanin, can alleviate AD-related pathologies by mitigating microglial senescence and to elucidate the underlying molecular mechanisms. We employed APP/PS1 mice, naturally aged mice, and an in vitro model using Aβ42-induced senescent BV2 microglia. Delphinidin’s effects were evaluated through assessments of cognitive function, synaptic integrity (synapse loss), Aβ plaque burden, senescent microglia gene signatures, and cellular senescence markers (including senescence-associated β-galactosidase activity, SASP factor expression, oxidative stress, and cyclin p21/p16 levels). Mechanistic studies involved analyzing the AMPK/SIRT1 signaling pathway, testing direct delphinidin-SIRT1 interaction, and using the AMPK inhibitor Compound C. Delphinidin treatment significantly alleviated cognitive deficits, synapse loss, Aβ peptides plaques of APP/PS1 mice via downregulated senescent microglia gene signature, prevented cell senescence, including senescence-associated β-galactosidase activity, senescence-associated secretory phenotype (SASP), oxidative stress, cyclin p21 and p16. And delphinidin treatment also prevented microglial senescence in naturally aged mice. In vitro, delphinidin treatment attenuated cell senescence induced by Aβ42 in BV2 microglia cells. Further research indicated that delphinidin treatment enhanced the AMPK/SIRT1 signaling pathway. Additionally, delphinidin was found to directly interact with SIRT1. It’s noteworthy that AMPK inhibitor Compound C inversed the protective effect of delphinidin against microglial senescence. Our study reveals for the first time that delphinidin effectively improved cognitive deficits, alleviated synapse loss and Aβ pathology in APP/PS1 mice by mitigating microglial senescence. These findings highlight delphinidin as a promising natural anti-aging agent against the development of aging and age-related diseases.

The early detection of subjects with probable cognitive deficits is crucial for effective appliance of treatment strategies. This paper explored a methodology used to discriminate between evoked related potential signals of stroke patients and their matched control subjects in a visual working memory paradigm. The proposed algorithm, which combined independent component analysis and orthogonal empirical mode decomposition, was applied to extract independent sources. Four types of target stimulus features including P300 peak latency, P300 peak amplitude, root mean square, and theta frequency band power were chosen. Evolutionary multiple kernel support vector machine (EMK-SVM) based on genetic programming was investigated to classify stroke patients and healthy controls. Based on 5-fold cross-validation runs, EMK-SVM provided better classification performance compared with other state-of-the-art algorithms. Comparing stroke patients with healthy controls using the proposed algorithm, we achieved the maximum classification accuracies of 91.76% and 82.23% for 0-back and 1-back tasks, respectively. Overall, the experimental results showed that the proposed method was effective. The approach in this study may eventually lead to a reliable tool for identifying suitable brain impairment candidates and assessing cognitive function.

Background: Stress is not scarce in peoples’ daily life that may result in mental diseases and cognitive impairments. Chronic restraint stress (CRS) is a well-validated animal model used to investigate the mechanism of stress-associated depression and cognitive impairments. Dl-3-n-butylphthalide (NBP) possesses anti-oxidant, anti-inflammatory and anti-apoptotic, promoting neurogenesis and neuroplasticity that exerts neuroprotective effects. However, the effects of NBP on CRS-induced depression and cognitive impairments remain unclear. Methods: C57BL/6 male mice were randomly divided into the control group, stress group and stress+NBP group. Mice were exposed to CRS for three consecutive weeks and mice in the NBP treatment group were administered with NBP before the CRS procedure. After that, depression and cognition behaviors were evaluated followed by phosphorylation of Ca²⁺/calmodulin-dependent protein kinase II (p-CaMKII), phosphorylation of cAMP-response element-binding protein (p-CREB), brain-derived neurotrophic factor (BDNF) proteins expression, immunohistochemistry of hippocampal postsynaptic density 95 (PSD95) and synaptophysin, and hippocampal morphology. Results: Our results showed that mice exhibited depression-like behaviors and cognitive deficits after 3 weeks exposure to CRS. Additionally, CRS downregulated CaMKII/CREB/BDNF signaling pathway, reduced PSD95 and synaptophysin expression and induced hippocampal CA1 and dentate gyrus ment significantly reversed the hippocampal pathological and molecular changes induced by CRS. Conclusion: In conclusion, these results reveal that NBP exerts a neuroprotective effect on depression and cognitive deficit through activating CaMKII/CREB/BDNF pathway, enhancing PSD95 and synaptophysin expression and protecting hippocampal morphology.