A BSTRACT Objectives: Cardiovascular disease is the leading cause of mortality in dialysis patients. While clinical trials have suggested uncertain benefit of statin therapy in this population, several large-scale observational studies have reported an association between statin use and reduced all-cause mortality. To further explore this issue, we aimed to assess the effectiveness of statin therapy in dialysis patients by synthesizing real-world data. Materials and Methods: We systematically searched PubMed and Embase for observational studies comparing adult statin users to nonusers in maintenance dialysis patients. Outcomes included all-cause mortality, cardiovascular death, stroke, myocardial infarction (MI), and major adverse cardiovascular events (MACE). Results: Nineteen studies with 310,370 dialysis patients were included. Statin use was associated with a lower risk of all-cause mortality (adjusted hazard ratio [aHR], 0.82; 95% confidence interval [CI], 0.77–0.87) and cardiovascular death (aHR, 0.83; 95% CI, 0.74–0.94). However, sensitivity analyses showed attenuated associations (aHR, 0.92; 95% CI, 0.89–0.96 for all-cause mortality; aHR, 0.90; 95% CI, 0.82–0.99 for cardiovascular death). No significant associations were observed between statin use and the risk of stroke, MI, or MACE. Conclusion: Statin therapy modestly reduced the risk of all-cause and cardiovascular mortality in patients undergoing maintenance dialysis but was not associated with a reduced risk of stroke, MI, or MACE.
A BSTRACT The early detection of hearing loss remains a major clinical challenge. In many patients, once functional changes become evident on pure-tone audiometry, their recovery is limited. Outer hair cells (OHCs) are essential for cochlear amplification, and their injury is a common pathway in many forms of sensorineural hearing loss. However, reliable biomarkers that reflect hearing impairment in real-time are still lacking. Prestin, a motor protein located in the lateral membrane of OHCs, has been proposed as a potential marker of cochlear stress, but findings across studies vary, and its clinical significance remains uncertain. In this review, we re-examine current evidence to determine under which biological and clinical conditions serum prestin provides meaningful information. We examined data from models of cisplatin exposure, aminoglycoside ototoxicity, noise injury, cyclodextrin-related stress, and age-related hearing loss, along with available human studies. In acute injury models, circulating prestin often shows a transient increase during early OHC membrane damage, suggesting that it reflects active cellular stress. In contrast, chronic degenerative conditions and aging are associated with reduced cochlear prestin expression, which represents a gradual loss of OHC reserve rather than ongoing membrane injury. Differences in assay platforms, isoform detection, and sampling timing may contribute to inconsistent findings. Overall, prestin should not be viewed as a marker of hearing loss severity. Rather, it may indicate acute OHC membrane stress in specific contexts. When interpreted according to etiology and timing, it may help identify early cochlear stress and may support earlier monitoring or otoprotective intervention in selected settings.
A BSTRACT Entrustable Professional Activities (EPAs) are widely used to operationalize competency-based education through workplace-based assessment. Although EPAs emphasize authentic clinical tasks, entrustment decisions are not value-neutral and inevitably reflect assumptions about professional competence and trust. This conceptual argument study examines the EPA-based assessment through the lens of Tzu Chi nursing education, a value-explicit healthcare context in which compassion, attentiveness to suffering, and moral responsibility are central to professional identity. We argue that entrustment decisions function not only as judgments of task readiness but also as sites where institutional humanistic values are enacted in everyday assessment practice. This article contributes by conceptualizing value-explicit healthcare systems as a distinct context for assessment design, translating humanistic values into entrustment decision-making practices, and proposing implementable narrative-based faculty language that preserves professional judgment without introducing additional scoring instruments. By focusing on entrustment decision-making rather than additional measurement tools, we propose how narrative justification and shared faculty language can support both assessment coherence and humanistic professional identity formation.
A BSTRACT Interstitial cystitis/bladder pain syndrome (IC/BPS) is a bladder disorder with an undetermined pathogenesis. Multiple phenotypes have been identified, each with distinct clinical symptoms, bladder conditions, pain distribution patterns, and psychological profiles. To date, no treatment can provide a durable, long-term cure for this condition. Medical therapies, including analgesics, antihistamines, anti-inflammatory agents, cyclosporine, and steroids, are generally of limited effectiveness. Current bladder-directed therapies for non-Hunner’s IC/BPS, including intravesical instillation of glycosaminoglycan supplements, botulinum toxin A, low-energy shock wave, intravesical platelet-rich plasma (PRP), or steroid injections, have been widely used, but the therapeutic results are not consistent. For Hunner’s lesion, ablation is the first treatment, with the addition of intravesical PRP or triamcinolone injections shown to enhance therapeutic efficacy. In addition, pelvic floor physiotherapy and local injections can help relieve pelvic floor inflammation and pain. The integration of psychiatric consultation and cognitive behavioral therapy with bladder-directed therapy may further improve clinical outcomes. Current guidelines recommend multimodal therapy tailored to the patient’s identifiable pathophysiology and clinical presentation. Phenotyping IC/BPS based on clinical characteristics, pain distribution, cystoscopic findings, and urine biomarkers holds promise for accurately identifying specific subtypes and guiding individualized, effective bladder therapies.
A BSTRACT Objectives: Programmed cell death protein-1/programmed death-ligand 1 inhibitors (PD-1/PD-L1i) improve survival in advanced renal cell carcinoma (RCC) but may increase the risk of acute kidney injury (AKI). This study evaluated the incidence of AKI, associated risk factors, and clinical outcomes among PD-1/PD-L1i users. Materials and Methods: Using the TriNetX Global Collaborative Network, we identified adults with Stage 3–4 RCC diagnosed between 2010 and 2025. Patients receiving PD-1/PD-L1i within 1 year of RCC diagnosis were compared with non-users. Exclusion criteria included age <18 years, bladder or transitional cell carcinoma, baseline estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m 2 , and death within 1 year of diagnosis. Propensity score matching (1:1) was performed using demographics and comorbidities. Outcomes included AKI incidence and overall survival (OS) over 3 years, and mortality, major adverse cardiovascular events (MACE), and sepsis over 2 years among PD-1/PD-L1i users with versus without AKI. A sensitivity analysis limited to patients with eGFR >30 mL/min/1.73 m 2 assessed robustness. Results: Among 724 PD-1/PD-L1i users and 6643 nonusers, 712 matched pairs were analyzed. PD-1/PD-L1i therapy was associated with a higher incidence of AKI compared with matched non-users, and this association remained significant in sensitivity analyses. Among PD-1/PD-L1i users, AKI did not significantly affect OS or MACE but increased in sepsis. Subgroup analyses identified diabetes mellitus, aminoglycoside exposure, and prior nephrectomy as independent predictors of AKI, whereas preserved renal function (eGFR >60 mL/min/1.73 m 2 ) was protective. Conclusion: PD-1/PD-L1i therapy increases AKI risk in advanced RCC but does not compromise short-term survival or major clinical outcomes. Recognizing high-risk subgroups may guide closer renal monitoring during immunotherapy.
A BSTRACT Objectives: This systematic review and meta-analysis evaluated the effectiveness of transsphenoidal surgery (TSS) in achieving remission and reducing recurrence in pituitary adenomas. Materials and Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. A comprehensive search of nine databases was performed for studies published between 2010 and 2025. Eligible studies included cohort, case–control, and randomized controlled trials reporting remission and/or recurrence outcomes after TSS. Study selection, data extraction, and quality assessment using the Newcastle–Ottawa Scale were independently conducted by two reviewers. Random-effects meta-analyses were applied where appropriate. Results: A total of 42 studies involving 6416 patients were included. Endoscopic TSS (ETSS) was reported in 62.32% of studies. Meta-analysis demonstrated that ETSS was associated with a significantly higher endocrine remission rate compared with microscopic TSS (MTSS) (RR = 1.25, 95% CI 1.12–1.40). No significant difference was observed in gross total resection rates (RR = 0.99, 95% CI 0.93–1.05). Descriptive pooled analysis showed recurrence rates of 7.1% for ETSS and 11.8% for MTSS, although no direct comparative studies were available for recurrence outcomes. Visual remission following ETSS was reported in 81.8% of patients with optic chiasm compression. Conclusion: These findings support the effectiveness of TSS, particularly through the endoscopic approach, in improving remission outcomes, with favorable recurrence profiles reported across included studies.
A BSTRACT Objectives: While numerous studies have investigated the impact of pregnancy on the cardiovascular system, the long-term alterations in heart structure and diastolic function among grand multiparous women remain under-researched, particularly in the context of contemporary guidelines and diagnostic techniques. This study aimed to investigate the alterations in left ventricular (LV) structure and diastolic function in multiparous women using echocardiography. Materials and Methods: Echocardiography was used to evaluate diastolic function and LV remodeling in 186 women with varying parity numbers. We compared echocardiographic parameters between parity groups: low parity (1–2 births) and grand multiparity (≥5 births). Results: In the low parous group, 33 women (35.5%) had Grade 1 LV diastolic dysfunction (DD), and only 10 participants (10.8%) had Grade 2 or 3 DD. In women with grand multiparity, only 12 of them (12.9%) did not have DD, and 23 participants (24.8%) had Grade 2 or 3 DD. Logistic regression analysis indicates that any DD and Grade 2 or 3 DD have the highest percentage in the grand multiparity group, with 7.8 and 2.7 times greater than the low parous group, respectively. Conclusion: Grand multiparity but not low parity significantly deteriorates LV diastolic function according to the present study. Parity information must be evaluated when determining a cardiovascular risk in women. Additional research is necessary to assess the likelihood of progressive DD with each pregnancy and to determine if parity explains the higher risk of diastolic heart failure in women.
A BSTRACT Alzheimer’s disease (AD) remains a major global health challenge, as currently available therapies have a limited impact on disease progression and rely largely on systemic administration. Effective treatment is further hindered by the blood–brain barrier, which restricts brain exposure for most therapeutic agents. Intranasal delivery offers a noninvasive nose-to-brain approach by utilizing olfactory and trigeminal pathways to bypass systemic circulation and first-pass metabolism. Clinically, intranasal insulin and mesenchymal stromal cell-derived exosomes have demonstrated feasibility and safety in mild cognitive impairment and AD, and imaging studies have confirmed direct brain uptake following intranasal dosing. However, variable clinical outcomes suggest that therapeutic efficacy is determined primarily by formulation properties rather than by the delivery route alone. This review adopts a material-centric perspective to summarize rational intranasal formulation strategies for AD, including chitosan derivatives, thermoresponsive poloxamer and amphiphilic block copolymer platforms, lipid-based nanocarriers, surface-engineered systems, and biomimetic nanovesicles. Key translational considerations are discussed with emphasis on quantitative validation of brain exposure and reproducibility. Emerging methodological tools are briefly noted as potential facilitators of formulation development, without detracting from the central role of rational material design.
A BSTRACT Liver transplantation is a life-saving procedure with significant hemodynamic instability and perioperative challenges, including massive blood loss, reperfusion syndrome, and cardiac complications. Effective intraoperative monitoring is crucial. Transesophageal echocardiography (TEE), a minimally invasive imaging modality, has emerged as a key tool for real-time monitoring. This systematic review evaluates intraoperative TEE in liver transplantation, focusing on hemodynamic monitoring, cardiac complication detection, fluid management, pulmonary hypertension, and surgical decision-making. A systematic literature search was conducted using PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar for studies published between 2010 and 2024. Search terms included “Liver Transplantation,” “Transesophageal Echocardiography,” “TEE,” and “Intraoperative Monitoring.” Relevant studies were screened, and data were synthesized through thematic analysis. Findings from the review show that TEE enables real-time hemodynamic assessment, guiding interventions for instability. It detects cardiac complications such as myocardial ischemia, arrhythmias, and valvular dysfunction, optimizes fluid resuscitation, manages pulmonary hypertension, and identifies air embolisms. In addition, it enhances intraoperative surgical and anesthetic decision-making. Intraoperative TEE is crucial for managing liver transplantation complexities. Its real-time imaging improves hemodynamic stability, enables timely interventions, and enhances patient safety, with future advancements expanding its applications.
A BSTRACT Objectives: To review existing strategies for managing coronal femoral bowing deformity in total knee arthroplasty (TKA) and assess their effectiveness in enhancing postoperative mechanical alignment (MA) and the femoral component positioning. Materials and Methods: A systematic literature review was performed across PubMed, Embase, the Cochrane Library, and Google Scholar up to August 2025. It included studies on surgical techniques for coronal femoral bowing in primary TKA, focusing on pre- and postoperative radiographic outcomes. Results: Thirteen studies were included in the final analysis. Individualized distal femoral valgus correction angles (VCAs) are more effective than fixed angles in restoring MA. Lateralizing the femoral entry point enables deeper, straighter insertion of the intramedullary rod (IM), resulting in better MA and more precise component placement. Intra-articular bone resection can be an effective alternative when lateralization is not feasible; however, it is limited by the severity of the deformity and technical complexity. Computer-assisted surgery (CAS) improves alignment accuracy and reduces outliers. Robotic-assisted TKA offers potential advantages but lacks specific data. Although patient-specific instrumentation has been suggested to enhance alignment in TKA, current evidence indicates no significant benefit over traditional methods. Extramedullary femoral guides provide more accurate alignment and lower outlier rates. Conclusion: Coronal femoral bowing is common among Asian patients and influences TKA outcomes. A full-length standing scanogram of the lower extremities is vital for preoperative planning. Depending on the patient’s condition, combining an IM cutting device, individualized VCA, lateralization of the entry point, intra-articular resection, and CAS may improve alignment and component positioning.
A BSTRACT Objectives: Robust evidence defining independent risk factors for wound dehiscence specifically among gynecologic surgical populations is lacking. Therefore, this study aimed to identify clinical and surgical factors associated with postoperative wound dehiscence in patients undergoing gynecological surgery. Materials and Methods: This retrospective study included 361 patients who underwent abdominal gynecological surgery. Demographic and perioperative data were collected and analyzed. The patients were categorized according to the presence or absence of wound dehiscence. Univariable analyses were performed using the independent t -test and Chi-squared test; variables with P < 0.05 were entered into multivariable logistic regression models to identify independent predictors. Results: Wound dehiscence occurred in 19 (5.3%) patients. Compared with those without dehiscence, affected patients had significantly lower body mass index (BMI) (22.73 ± 4.59 vs. 25.24 ± 5.21), longer operative time (262.3 ± 123.0 vs. 192.8 ± 93.4 min), and prolonged hospital stay (32.95 ± 24.46 vs. 9.24 ± 6.35 days). Wound classification and preoperative infection within 7 days were significantly associated with wound dehiscence. Multivariable analysis identified lower BMI, longer operative time, and preoperative infection within 7 days as independent predictors of wound dehiscence. In subgroup analysis, preoperative infection within 7 days predicted wound dehiscence only in hysterectomy for malignancy, whereas longer operative time was the only predictor in myomectomy or non-malignant procedures. Conclusion: Postoperative wound dehiscence was associated with both patient-related and procedure-related factors in this cohort. Lower BMI, prolonged operative time, and preoperative infection within 7 days were independently associated with increased risk of wound dehiscence. In subgroup analysis, longer operative time may be associated with wound dehiscence in benign cases, whereas preoperative infection within 7 days was associated with wound dehiscence in malignant cases. These findings highlight potentially modifiable perioperative variables that warrant further investigation in prospective studies before clinical recommendations can be established.
A BSTRACT Objectives: This study aimed to compare maternal characteristics, delivery outcomes, and neonatal conditions in 2013 and 2023 at our hospital and to evaluate the association between labor induction and neonatal outcomes. Materials and Methods: A retrospective cohort study was conducted, including 600 women who delivered in 2013 ( n = 316) and 2023 ( n = 284). Cases involving scheduled cesarean delivery, vaginal birth after cesarean, missing data, or immediate neonatal death were excluded. Maternal demographics, obstetric parameters, and neonatal outcomes were compared. Logistic regression was performed to assess the association between induction of labor and adverse outcomes. Results: The mean maternal age increased significantly from 29.73 to 31.29 years ( P < 0.001), and the induction rate more than doubled from 19.94% to 50.70% ( P < 0.001). Although cesarean rates were unchanged, vacuum extraction deliveries increased (15.82% vs. 27.46%, P < 0.001), and spontaneous vaginal deliveries decreased (80.70% vs. 68.31%, P < 0.001). Neonatal intensive care unit (NICU) admissions rose significantly (2.53% vs. 7.39%, P < 0.001), while low 1-min Apgar scores (≤6) remained stable. Regression and sensitivity analyses revealed that induction of labor was independently associated with a higher risk of low Apgar scores (adjusted odds ratio = 3.24, 95% confidence interval = 1.27–8.28, P = 0.014), but not with increased rates of NICU admission or vacuum-assisted delivery. Conclusion: Over the past decade, both maternal age and labor induction rates have increased markedly. While cesarean rates remained steady, induction of labor was associated with greater neonatal morbidity, reflected by increased low Apgar scores. These findings emphasize the need for careful clinical judgment and close monitoring during labor induction to optimize perinatal outcomes.
A BSTRACT Objectives: Diabetes mellitus (DM) is common and has been suspected to influence cancer risk. This study aimed to investigate the association between DM and pancreatic cancer among patients aged 20–84 years. Materials and Methods: We conducted a retrospective cohort study using the TriNetX Asia-Pacific Collaborative Network (2007–2025). Patients aged 20–84 years were divided into two groups: Those with a diagnosis of DM (DM group) and those without (control group). Propensity score matching was applied to balance baseline characteristics. The primary outcome was the incidence of pancreatic cancer. Cumulative incidence, hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated using the TriNetX “Compare Outcomes” module. To mitigate potential reverse causality, we applied prespecified lag periods (primary analysis: 1-year lag; secondary analyses: 1-month, 3-month, and 6-month lags). Results: After matching, each group included 511,344 patients. Over the observation period (maximum up to 20 years), the cumulative incidence of pancreatic cancer was 0.045% in the DM group and 0.006% in the control group in the 1-year lag primary analysis. The Cox model showed that DM was associated with a higher hazard of pancreatic cancer (HR 4.677; 95% CI: 3.214–6.807). Conclusion: DM was associated with a higher observed hazard of pancreatic cancer in this large real-world cohort. However, the absolute risk was low, and findings should be interpreted considering potential detection bias and under-ascertainment of confounders in federated electronic health record data.
A BSTRACT Traditional Chinese medicine (TCM) provides a holistic therapeutic framework with over 2000 years of clinical use; however, its molecular mechanisms remain incompletely defined. This narrative review, which is based on a systematic search of global and Chinese databases, evaluates preclinical and clinical evidence across seven disease categories: osteoporosis, Alzheimer’s disease, inflammatory bowel disease, cardiovascular disease (CVD), cancer, liver disease, and viral infections. Curcumin ( Curcuma longa ) and tanshinone IIA ( Salvia miltiorrhiza , TIIA) emerge as key bioactive compounds targeting shared pathological pathways, including nuclear factor kappa B-mediated inflammation, nuclear factor erythroid 2–related factor 2 (Nrf2)-related oxidative stress, and mitochondrial dysfunction, providing a unified mechanistic basis for TCM’s multidisease effects. Clinical evidence supports the adjunctive use of curcumin in ulcerative colitis, nonalcoholic fatty liver disease, and coronavirus disease 2019 and of TIIA in CVD. However, current studies are limited by small sample sizes and formulation heterogeneity. Poor oral bioavailability, potential toxicity, and regulatory challenges remain major barriers to clinical translation. Advancing TCM into evidence-based practice requires improved formulations, well-designed multicenter randomized controlled trials, and robust pharmacovigilance to ensure safety and efficacy.
A BSTRACT Objectives: This study aimed to compare the relative efficacy of individual SGLT2 inhibitors and dual SGLT1/2 inhibitors in preventing atrial fibrillation (AF). Materials and Methods: This network meta-analysis adhered to the Preferred Reporting Items for Systematic reviews and Meta-analyses 2020 guidelines. A comprehensive literature search was conducted in PubMed, the Cochrane Library, and ClinicalTrials.gov up to September 1, 2025. Data analyses were performed using MetaInsight v6.4.2. Odds ratios (ORs) with 95% credible intervals were estimated using Bayesian models, and surface under the cumulative ranking curve (SUCRA) values were calculated to rank treatment effects. Sensitivity, subgroup analyses, and network meta-regression analyses were also conducted. Results: Sixty-two randomized controlled trials, including 117,623 participants, were analyzed. Among six SGLT inhibitors evaluated, dapagliflozin significantly reduced the risk of AF compared with placebo (OR 0.706, 95% CrI: 0.511–0.965; SUCRA: 85.10), ranking highest among all interventions. Sensitivity analysis, subgroup, and meta-regression showed consistent results, with no significant modifying effects of diabetes, heart failure, chronic kidney disease, baseline AF status, risk of bias, follow-up duration, age, sample size, and gender on the outcome. Conclusion: Among SGLT2 and dual SGLT1/2 inhibitors, dapagliflozin demonstrated the most consistent association with reduced odds of AF, independent of baseline comorbidities. These findings suggest a potential class effect favoring dapagliflozin for AF prevention.
Nocturnal enuresis (NE) is a common and multifactorial pediatric condition characterized by abnormalities in bladder storage, renal water regulation, and central arousal mechanisms. According to the International Children's Continence Society, NE is defined as intermittent urinary incontinence that occurs during sleep in children aged 5 years or older, in the absence of congenital or acquired neurologic or urologic disease. Although often self-limiting, NE imposes a substantial psychosocial burden, causing embarrassment, low self-esteem, sleep disruption, and family stress. Advances in neurophysiology and renal chronobiology have clarified that NE represents a developmental delay involving three major pathophysiological domains: nocturnal polyuria, reduced functional bladder capacity or detrusor overactivity, and impaired arousal responses to bladder filling. Contemporary management emphasizes individualized, mechanism-based strategies tailored to the predominant abnormality. This review summarizes current evidence on the pathophysiology, clinical evaluation, and evidence-based treatment of pediatric NE and highlights the importance of early identification, structured behavioral interventions, and family-centered multidisciplinary support to improve long-term outcomes and quality of life.
Jing-Si Herbal Tea (JSHT) is a traditional multi-herbal preparation composed of flavonoids, polyphenols, triterpenoid saponins, glycyrrhizin, and other bioactive constituents that collectively contribute to a wide spectrum of biological activities. Emerging laboratory and clinical studies indicate that JSHT is associated with modulation of oxidative stress, inflammatory responses, and immune-related pathways, with reported antiviral and cytoprotective effects primarily observed in experimental models and exploratory clinical settings. This review synthesizes current evidence describing the diverse pharmacological actions of JSHT and its potential applications across oncologic, inflammatory, metabolic, and infectious disease contexts. Experimental findings suggest that JSHT may be associated with modulation of tumor progression-related processes, including epithelial-mesenchymal transition and aberrant nuclear factor kappa B activity, while being associated with intracellular oxidative stress-related activation of apoptosis- and ferroptosis-related pathways in cancer cell models. Its immunoregulatory capacity is reflected in the attenuation of pro-inflammatory cytokines and the promotion of anti-inflammatory macrophage phenotypes. In respiratory and infectious diseases such as coronavirus disease 2019 and chronic obstructive pulmonary disease, JSHT has been reported to attenuate hyperinflammatory responses and preserve cellular or organ function and has been associated with clinical improvement in selected observational studies, which should be interpreted cautiously. Early clinical data, including results from a randomized study in functional dyspepsia, suggest benefits for gastrointestinal symptoms and anxiety, accompanied by increases in serum butyrate that may indicate involvement of the gut-brain axis. Across available studies, JSHT has shown good tolerability with few reported adverse effects. Overall, the accumulating evidence suggests that JSHT may have potential relevance as a multitarget complementary approach, pending confirmation through well-controlled clinical studies. Nonetheless, more extensive, well-controlled clinical investigations are warranted to validate its efficacy and clarify its mechanistic pathways.
Growing human and experimental evidence redefine Alzheimer's disease (AD) as a neurovascular disorder because the early neurovascular unit (NVU) injury triggers proteinopathy. Among NVU, pericytes are a pivotal regulator of capillary tone, blood-brain barrier (BBB) integrity, and amyloid-β (Aβ) clearance. Injured or lost pericytes promote non-selective transcytosis, induce endothelial de-zonation, weaken tight junctions, and drive heterogeneous capillary flow and rarefaction. Here, we collect data from clinical imaging, cerebrospinal fluid (CSF) biomarkers, and transgenic mice with platelet-derived growth factor receptor-β (PDGFRβ) signal defects to discuss the role of CSF soluble PDGFRβ (sPDGFRβ) as a marker of BBB damage across the AD continuum. During normal aging, sPDGFRβ rises slightly, consistent with low-grade pericyte stress. In mild cognitive impairment, sPDGFRβ is elevated and associates with BBB breakdown and accelerated cognitive decline, often independent of core AD biomarkers, suggesting early vascular changes before AD onset. In early AD, pericyte dysfunction (characterized by elevated sPDGFRβ) attenuates pericyte-dependent Aβ processing and endothelial lipoprotein receptor-related protein 1-mediated Aβ efflux, leading to impaired perivascular drainage and favoring Aβ40-rich vascular deposition and capillary cerebral amyloid angiopathy. During AD progression, despite persistent leakage, sPDGFRβ frequently plateaus, reflecting severe pericyte depletion and reduced discrimination of disease stage. We propose a practical approach that integrates sPDGFRβ with BBB imaging analysis and Aβ biomarkers to distinguish between parenchymal-dominant and vascular-dominant pathology in AD. These indicators can identify patients at high risk of developing amyloid-related imaging abnormalities during anti-amyloid therapy and can serve as pharmacodynamic endpoints for BBB-stabilizing or pericyte-targeted interventions to advance personalized dementia care.
