BackgroundWe examined baseline relative circulating osteocalcin (OCN) in relation to incident dementia in UK Biobank.MethodsThe longitudinal cohort comprised 43,942 participants; models used available complete records. Cox models used baseline OCN standardized per SD and follow-up censored at diagnosis, death, or November 27, 2024. Cognitive, MRI, and baseline molecular analyses were exploratory.ResultsIn the fully adjusted model, OCN was not clearly associated with all-cause dementia (HR 1.052; 95% CI, 0.988–1.120; p = 0.117; N = 40,253; 1,095 events). The vascular dementia estimate was nominally positive (HR 1.159; 95% CI, 1.010–1.328; p = 0.035), but did not survive Holm correction across three secondary outcomes (adjusted p = 0.105) and weakened after excluding baseline stroke. Adding OCN changed the mean fivefold cross-validated C index from 0.84628 to 0.84642 (ΔC = 0.00014). No baseline cognitive association survived Holm correction across four tests. Nominal hippocampal and WMH associations in the larger MRI sample were not evident in matched extensively adjusted samples. Repeated-visit cognitive models did not yield adequately sized multiple classes for interpretable class-membership regressions. Baseline measured-only molecular analyses identified OCN-related correlations, but age- and sex-adjusted BCAA correlations did not survive panel-wise Bonferroni correction.ConclusionBaseline relative OCN did not show a clear fully adjusted all-cause dementia association or useful incremental discrimination. Subtype, cognitive, imaging, and molecular findings remain exploratory. These data do not establish a compensatory mechanism or clinical predictive utility.
BackgroundAlzheimer’s disease is a neurodegenerative disorder marked by progressive cognitive decline. The pathogenesis of AD is complex, and effective methods for early diagnosis and treatment are currently lacking. Extracellular vesicles, which are key mediators of intercellular communication, significantly influence the onset and progression of AD. Consequently, a systematic review of this field is essential.MethodsThis study utilized the WoSCC and Scopus databases to gather English “Articles” and “Reviews.” Following duplicate removal via Python, bibliometric methods systematically analyzed research hotspots and frontiers concerning extracellular vesicles in Alzheimer’s disease. The analysis encompassed publication trends, countries, institutions, authors, journals, keywords, and references. Concurrently, the PubMed database was searched to verify the robustness and consistency of the analysis results.ResultsThis study conducted a bibliometric analysis of 2,626 articles, with 1,614 articles from PubMed used for consistency verification. The findings indicate a continuous rise in research interest in this field. Key areas of focus include emerging pathological mechanisms, peripheral blood biomarkers, targeted drug delivery, miRNA, and clinical trials. Cross-database verification confirmed a strong consistency in publication trends, countries, institutions, and authors, with a significant overlap of keywords and prominent research hot spots.ConclusionThis study demonstrates a shift in the research focus on Extracellular vesicles within Alzheimer’s disease from single-pathology investigations to exploring multiple mechanisms. Their significance in precise diagnosis and targeted therapy is increasingly evident. However, clinical trials remain limited. Future efforts should prioritize enhancing clinical validation and standardizing isolation techniques.
BackgroundApathy is a disabling non-motor symptom of Parkinson’s disease (PD), but its neuroimaging correlates remain unclear. Glymphatic-related MRI metrics abnormalities and white matter microstructural damage have each been implicated in PD, yet their relationship with apathy is incompletely understood.ObjectiveTo investigate the relationships among glymphatic-related MRI metrics, white matter abnormalities, and apathy in PD, while accounting for affective, cognitive, motor, and treatment-related factors.MethodsWe prospectively enrolled 41 patients with PD [19 with apathy (APD), 22 without apathy (nAPD)] and 38 healthy controls (HC). Multimodal MRI quantified choroid plexus volume (CPV), perivascular space measures, DTI-ALPS, gBOLD-CSF coupling, free water (FW), free-water-corrected diffusion indices, and NODDI metrics. Tract-based spatial statistics, sparse principal component analysis, partial correlation, sensitivity analyses, and exploratory mediation analyses were performed.ResultsCompared with HC, PD patients showed widespread white matter abnormalities, including increased FW, fwAD, fwMD, fwRD, and ODI and decreased fwFA and NDI. APD patients showed higher FW than nAPD patients in clusters involving the corpus callosum, left superior longitudinal fasciculus, uncinate fasciculus, inferior fronto-occipital fasciculus, and other widespread tracts. Within PD, these FW abnormalities were associated with apathy severity; several associations persisted after adjustment for UPDRS-III and levodopa equivalent daily dose but were attenuated after adjustment for affective or cognitive symptoms. CPV measures were also associated with apathy-related FW abnormalities, with selected associations remaining after adjustment for MoCA or motor/medication measures. Direct associations between individual glymphatic-related MRI metrics and apathy severity were less consistent. Exploratory mediation effects were observed mainly in the combined PD + HC cohort and were not robust within PD or apathy subgroups after multiple-comparison correction.ConclusionApathy in PD was most consistently associated with increased extracellular FW within distributed white matter networks, superimposed on widespread PD-related microstructural damage. Glymphatic-related MRI metrics abnormalities, particularly CPV, were coupled with apathy-related FW but showed weaker direct relationships with apathy severity. These findings support an associative glymphatic–white matter framework for PD apathy, while suggesting partial overlap with broader affective and cognitive dysfunction rather than an apathy-specific causal cascade.
BackgroundNeuroinflammation serves as a common pathological substrate across various neurological disorders, including neurodegenerative diseases, cerebrovascular diseases, and neuroimmune conditions. Key pathogenic mechanisms underlying these disorders include aberrant microglial activation, sustained release of pro-inflammatory cytokines, and dysregulation of critical signaling cascades, particularly the NLRP3 inflammasome, NF-κB, and Nrf2/HO-1 pathways, all of which collectively contribute to progressive neuronal damage and functional decline.ObjectivesThis review aims to systematically evaluate the preclinical evidence for the neuroprotective effects of Gastrodia elata Blume and its major bioactive constituents—gastrodin, parishin, p-hydroxybenzyl alcohol, and G. elata polysaccharides—in the treatment of Parkinson’s disease, Alzheimer’s disease, acute ischemic stroke, vascular dementia, and epilepsy, with a particular focus on their modulation of inflammation-related signaling pathways.MethodsA comprehensive literature search was performed in PubMed, Web of Science, ScienceDirect, China National Knowledge Infrastructure (CNKI), and Wanfang databases from inception to May 2026. Original studies investigating G. elata or its components in animal or cellular models of the aforementioned diseases and reporting inflammatory mechanisms were included.ResultsG. elata and its active constituents regulate multiple neuroinflammation-associated signaling pathways, including Nrf2/HO-1, NF-κB/NLRP3, JAK2/STAT3, and MAPK, thereby suppressing inflammatory responses. Mechanistically, these effects are primarily manifested as: (1) inhibition of microglial M1 polarization and consequent reduction of pro-inflammatory cytokine release; (2) blockade of inflammation-induced neuronal death through suppression of ferroptosis, pyroptosis, and apoptosis; (3) enhancement of Nrf2 nuclear translocation, leading to upregulation of antioxidant enzymes and attenuation of oxidative stress-mediated inflammation (e.g., ROS-driven cascades); and (4) modulation of the gut microbiota–brain axis to reduce both peripheral and central low-grade chronic inflammation.ConclusionDespite certain limitations in the existing evidence, this review clearly identifies future research priorities, including investigation of non-gastrodin active components, causal validation using gene-knockout models, and development of brain-targeted delivery strategies. These findings provide a valuable reference for the mechanism-guided development of neuroprotective agents derived from G. elata.
