Taipei Veterans General Hospital

Background Noninfectious anterior uveitis shares genetic factors, including HLA-B27, with ankylosing spondylitis (AS). The aim of this study was to identify significant single nucleotide polymorphisms (SNPs) associated with noninfectious anterior uveitis in AS patients, which could help predict the risk of developing this condition and provide deeper insights into its genetic underpinnings. Methods A genome-wide association study (GWAS) was conducted utilizing the genomic data of 468 AS patients, including 90 with noninfectious anterior uveitis and 378 without it, from the Taiwan Precision Medicine Initiative. This study identified associated genes via SnpXplorer and developed a polygenic risk score (PRS) model to identify AS patients with increased risk of noninfectious anterior uveitis. Biological pathways were analyzed via Enrichr-KG and various databases. Results GWAS revealed two novel SNPs, rs1736952 and rs17354984, with p values < 5x10 ⁻⁸ , and seventy-four SNPs with p values < 1x10 ⁻⁴ . The associated genes were involved mainly in antigen presentation, interferon signaling, immune regulation pathways, ciliary movement, and neurodegeneration. An optimal PRS model was built using nineteen SNPs with an area under the curve of 0.907. Conclusion Our results revealed that two novel and significant SNP loci, rs1736952 and rs17354984, are strongly associated with noninfectious anterior uveitis in patients with ankylosing spondylitis. However, their roles in uveitis and other immune disorders warrant further investigation.

Background Neuroendocrine prostate cancer (NEPC) (de novo or treatment related [t-NEPC]) is a rare and deadly variant of prostate cancer. While de novo NEPC is rare, t-NEPC occurs more frequently in patients with castration-refractory prostate cancer. Owing to the rarity of NEPC, no standard treatment has been established, and the outcomes are generally unsatisfactory. Methods This study retrospectively reviewed NEPC cases at Taipei Veterans General Hospital between 2018 and 2023. Clinical outcomes, treatment modalities, and related genomic profiles were recorded. We also performed a literature review of case series reporting the outcomes of chemotherapeutic regimens for NEPC. Results From 2158 cases of prostate cancer cases diagnosed during the study period, only seven had pathologically proven NEPC (0.3%), and the median overall survival was 364 d. Three patients who underwent multi-gene panel sequencing had mutations in RB1 , and DLL3 immunohistochemical staining showed a positivity rate of 50%. We performed a literature review on chemotherapy outcomes in patients with NEPC. In six studies with 104 patients, etoposide + platinum treatment was most commonly used. The progression free survival (PFS) and overall survival ranged from 3.4 to 9.3 and 8.4 to 22.4 months, respectively. The response rates ranged from 44% to 69.2%. These studies were consistent with a dismal overall survival rate, despite a high response rate to the initial chemotherapy regimen. Conclusion Our study reported poor outcomes with chemotherapy, with a high frequency of RB loss and DLL3 positivity. Further clinical developments targeting DLL3 are warranted.

Background Unlike conventional photon radiotherapy, particle therapy has the advantage of dose distribution. Carbon-ion radiotherapy is also advantageous in terms of biological effectiveness and other radiobiological aspects. These benefits lead to a higher response probability for previously known radioresistant tumor types. Therefore, Taipei Veterans General Hospital, which is located in the northern district of Taipei, built the first carbon-ion irradiation facility in Taiwan. Methods Taipei Veterans General Hospital completed a phase 1 trial to evaluate the safety of carbon-ion radiotherapy. Six patients (4 males and 2 females with prostate adenocarcinoma, sacral chordoma, hepatocellular carcinoma, lung adenocarcinoma, or parotid high-grade carcinoma) were enrolled in this study. The mean age of the patients was 62.7 years. The mean dose was 57.3 Gy(RBE) (fraction range, 4-16 Gy(RBE)). Results During this phase 1 trial, all patients were monitored for 3 months to evaluate acute toxicity and short-term outcomes after treatment with carbon irradiation. Only 2 patients experienced grade 2 toxicity, which resolved without medication 1 month after completing treatment. The tumor response demonstrated 1 complete response, 1 partial response, and 4 cases of stable disease. Conclusion Carbon-ion radiotherapy was determined to be an effective and safe treatment.

Background: The phase 3 open-label KEYNOTE-426 study demonstrated that first-line pembrolizumab plus axitinib improved overall survival (OS) and progression-free survival (PFS) versus sunitinib for metastatic renal cell carcinoma (mRCC) in a global population. This subgroup analysis investigated the efficacy and safety of pembrolizumab-axitinib versus sunitinib in patients enrolled in KEYNOTE-426 in East Asia (Japan, South Korea, and Taiwan). Methods: Adults with clear cell mRCC were randomly assigned 1:1 to receive intravenous pembrolizumab 200 mg every 3 weeks with oral axitinib 5 mg twice daily or oral sunitinib 50 mg once daily (4 weeks on/2 weeks off). Dual primary endpoints were OS and PFS, assessed by blinded independent central review. Secondary endpoints were objective response rate (ORR) and safety. Results: The East Asian subgroup comprised 130 patients (pembrolizumab-axitinib, n = 62; sunitinib, n = 68; 15.1% of the global intention-to-treat population). Compared with sunitinib, pembrolizumab-axitinib OS hazard ratio (HR) was 0.85 [95% confidence interval (CI) 0.50-1.44; 36-month rates, 62.9% and 58.8%, respectively] and PFS HR was 0.59 (95% CI 0.38-0.92) in favor of pembrolizumab-axitinib. ORR favored pembrolizumab-axitinib (64.5% vs 44.1% for sunitinib). The results were generally consistent with the intention-to-treat population. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 69.4% of patients on pembrolizumab-axitinib and 74.6% on sunitinib; 16 (25.8%) patients on pembrolizumab-axitinib and 17 (25.4%) patients on sunitinib discontinued due to adverse events. No deaths from TRAEs occurred. Conclusion: Pembrolizumab-axitinib improved efficacy for East Asian patients with untreated clear cell mRCC, consistent with results from the global population. Safety was manageable. ClinicalTrials.gov identifier: NCT02853331.

Background Acute carbon monoxide poisoning (COP) has been a common cause of emergency hospital visits over the past decade. Besides the immediate symptoms of poisoning, carbon monoxide exposure can cause various long-term complications, especially delayed neurological sequelae (DNS) and myocardial injury (MI). Methods This study retrospectively enrolled 502 patients with COP, including complete collection data, from the Taiwan National Poison Control Center between January 1, 2000, and December 31, 2015. After collecting the relevant clinical and laboratory data, multivariate logistic regression analysis was performed to investigate the associations between potential predictors and risk factors, hazard ratio (HR), and confidence intervals (CI). Results The cumulative incidence rates were 12.0% and 19.7% for DNS and MI, respectively. A Glasgow Coma Scale (GCS) score of <9 (HR 2.55; 95% CI: 1.52–4.27) and rhabdomyolysis (HR 2.68; 95% CI: 1.59–4.53) were identified as individual indicators of DNS in patients with COP. However, a greater risk for MI was associated with a GCS score of <9 (HR 2.50; 95% CI: 1.67–3.74), rhabdomyolysis (HR 4.91; 95% CI: 3.28–7.35), acute renal impairment (HR 2.43; 95% CI: 1.59–3.71), and leukocytosis (HR 9.55; 95% CI: 3.88–23.50). Hyperbaric oxygen therapy for patients with COP was more beneficial for DNS (HR 0.64; 95% CI: 0.34–1.20) than for MI (HR 1.94; 95% CI: 0.94–4.01). Conclusion Early differentiation of risk factors between DNS and MI contributes to an effective evaluation of patients with acute COP and the provision of appropriate therapy.

Background Caffeic acid phenethyl ester (CAPE) is the main bioactive component of poplar type propolis. We previously reported that treatment with caffeic acid phenethyl ester (CAPE) suppressed the cell proliferation, tumor growth, as well as migration and invasion of prostate cancer (PCa) cells via inhibition of signaling pathways of AKT, c-Myc, Wnt and EGFR. We also demonstrated that combined treatment of CAPE and docetaxel altered the genes involved in glycolysis and tricarboxylic acid (TCA) cycle. We therefore suspect that CAPE treatment may interfere glucose metabolism in PCa cells. Methods Seahorse Bioenergetics platform was applied to analyzed the extra cellular acidification rate (ECAR) and oxygen consumption rate (OCR) of PCa cells under CAPE treatment. UPLC-MSMS with Multiple Reaction Monitoring (MRM), PCR, and western blot were used to analyze the effects of CAPE on metabolites, genes, and proteins involved in glycolysis, TCA cycle and pentose phosphate pathway in PCa cells. Flow cytometry and ELISA were used to determine the level of reactive oxygen species in PCa cells being treated with CAPE. Results Seahorse Bioenergetics analysis revealed that ECAR, glycolysis, OCR, and ATP production were elevated in C4-2B cells under CAPE treatment. Protein levels of glucose-6-phosphate dehydrogenase (G6PD), phosphogluconate dehydrogenase (PGD), glutaminase (GLS), phospho-AMPK Thr172 as well as abundance of pyruvate, lactate, ribulose-5-phosphate, and sedoheptulose-7-phosphate were increased in CAPE-treated C4-2B cells. ROS level decreased 48 h after treatment with CAPE. Co-treatment of AMPK inhibitor with CAPE exhibited additive growth inhibition on PCa cells. Conclusions Our study indicated that PCa cells attempted to overcome the CAPE-induced stress by upregulation of glycolysis and G6PD but failed to impede the growth inhibition caused by CAPE. Concurrent treatment of CAPE and inhibitors targeting glycolysis may be effective therapy for advanced PCa.

Background Patients with atrial fibrillation (AF) who suffered a previous stroke are at increased risk of recurrent thromboembolic events and other major outcomes. The impact of the number of stroke episodes on the natural history of patients with AF is still unclear. Methods and Results Using data from the international, multicenter, and prospective GLORIA‐AF (Global Registry on Long‐Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation) Registry Phase III, we categorized patients with a recent diagnosis of non‐valvular AF according to the number of previous strokes (either 0, 1, or ≥2 episodes). We analyzed use of oral anticoagulants through multiple logistic regression model, and risk of major outcomes using multiple Cox‐regression models; our primary outcome was all‐cause death. Among 21 223 patients (mean age: 70.2±10.3 years; 44.9% female) included, 2251 (10.6%) had a previous history of stroke, and 216 (1.0%) had ≥2 or more strokes. Oral anticoagulants were used in ≥80% of patients regardless of the numbers of previous stroke, although those with 1 (versus >1) prior stroke showed lower odds of receiving oral anticoagulants (odds ratio [95% CI]: 0.83 [0.73–0.94]). During 3‐years follow‐up, the risk of all‐cause mortality increased with the number of previous strokes (hazard ratio [95% CI]: 1.46 [1.28–1.67] and 2.43 [1.79–3.29] for 1 versus 0 and ≥2 versus 0 previous strokes, respectively). Similar results were observed for other secondary outcomes, including thromboembolism, but not for major bleeding. Conclusions History of stroke still represents a key risk factor in patients with AF. Patients who suffered more than 1 episodes of stroke had significantly worse prognosis and further efforts may be required to improve their clinical outcomes.

Impact of age on surgical and survival outcomes after combined robotic/open pancreaticoduodenectomy (CR/OPD) has not been extensively studied. This study aimed to evaluate the surgical and survival outcomes of patients aged < 50 years who underwent CR/OPD. A comparative study was conducted on patients who underwent CR/OPD divided into two groups: the young (age < 50 years) and the old (age ≥ 50 years). A total of 555 patients were included in this study, with 53 (9.5%) in the young group and 502 (90.5%) in the old group. Periampullary adenocarcinomas were less common in the young group (32.1% vs. 76.5%), whereas solid and pseudopapillary tumors (9.4% vs. 1.0%) and neuroendocrine tumors (15.1% vs. 3.6%) were more common. Soft pancreatic parenchyma (77.4% vs. 76.5%) and non-dilated (≤ 3 mm) pancreatic ducts (77.4% vs. 62.5%) were more prevalent in the young group. The young group had a shorter length of stay (median, 16 vs. 20 days). No significant differences were observed in the other surgical outcomes and risks, including postoperative pancreatic fistula (POPF) (7.5% vs. 8.0%). Survival outcomes for overall periampullary adenocarcinoma favored the young group, with a 5-year survival rate of 76.4% vs. 46.7% in the old group. In conclusion, RPD in the young patients (< 50 years) is associated with comparable surgical outcomes and favorable survival outcomes for periampullary adenocarcinoma compared with the older patients (≥ 50 years). These findings highlight the feasibility and safety of RPD in the young population, although the prevalence of soft pancreatic parenchyma and non-dilated pancreatic ducts was higher in the young group.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small vessel disease caused by mutations in the NOTCH3 gene. This review highlights the increasing recognition of intracerebral hemorrhage (ICH) as a significant manifestation of CADASIL, often predominantly characterized by ischemic strokes and vascular dementia. Recent studies indicate that the prevalence of ICH in CADASIL patients ranges from 0.5% to 33.3%, the variability of which is mainly influenced by ethnicity. In East Asian cohorts, where specific NOTCH3 mutations like p.R544C and p.R75P are more prevalent and have been associated with a higher rate of ICH, suggesting a link between these mutations and the hemorrhagic risk. Hypertension, as with other etiologies of ICH, is a key risk factor in CADASIL patients, with 40-90% of those who experience ICH also having a history of hypertension. The presence of cerebral microbleeds (CMBs) and a high CMBs load are strongly associated with increased risk of ICH. Neuroimaging studies show that ICH in CADASIL patients predominantly occurs in the thalamus and basal ganglia. There is a notable spatial correlation between CMBs and subsequent ICH, suggesting that CMBs may serve as markers of microangiopathy in regions prone to vascular injury. CADASIL patients with ICH experience greater morbidity, higher mortality rates, and increased annual stroke recurrence risk compared to those with ischemic events. In summary, this review emphasizes the need for tailored management strategies that prioritize rigorous blood pressure control and the careful use of antithrombotic agents in CADASIL patients with a high burden of CMBs. By advancing our understanding of ICH in CADASIL, we aim to improve diagnostic and therapeutic approaches, ultimately enhancing patient outcomes and quality of life in this high-risk population.

Background Coronary artery disease (CAD) and atrial fibrillation (AF) often coexist, but the impact of clinical phenotypes of CAD on outcomes in AF patients in the non‐vitamin K antagonist oral anticoagulant drugs (NOACs) era is less well understood. Methods This was a post‐hoc of the GLORIA‐AF registry, a global, multicenter, prospective AF registry study. Patients were divided into three groups: prior history of myocardial infarction (MI)/unstable angina group (Group 1); stable angina group (Group 2); and a control group without stable angina or history of MI/unstable angina. The primary endpoint was the composite of all‐cause death or stroke, and the safety endpoint was major bleeding. Results A total of 24,827 patients were included in this analysis (median age was 71 (IQR, 64–78) years; 55% male) and 5394 (21.7%) had CAD. During a follow‐up of 2 years, the incidence of the primary endpoint was 5.99 (95% CI, 5.33, 6.71) per 100 patient‐years in Group 1, 4.04 (95% CI, 3.55, 4.70) per 100 patient‐years in Group 2, and 2.79 (95% CI, 2.62, 2.96) per 100 patient‐years in the control group ( p < .001). Compared the control group, the adjusted hazard ratio of the primary composite endpoint in Groups 1 and 2 were 1.58 (95% CI, 1.37, 1.83, p < .001) and 1.22 (95% CI, 1.04, 1.43, p = .012), respectively. Among anticoagulated patients with AF and CAD, NOACs were associated with a reduced risk of the primary composite endpoint and major bleeding, compared with vitamin K antagonists (VKA). Conclusions CAD was prevalent in patients with AF, and clinical phenotypes of CAD influenced outcomes in patients with AF, with a history of MI/unstable angina being associated with a significantly increased risk of CV events, compared to stable angina. NOACs were superior to VKA in terms of the effectiveness and safety outcomes in patients with AF and concomitant CAD.

Aim Adequate pelvic floor support for the urethra is crucial for preventing stress urinary incontinence (SUI). Obesity is an established risk factor for SUI. This study aimed to explore the relationship between SUI and body composition, specifically focusing on muscle and fat mass. Methods This single‐center, prospective, cross‐sectional study enrolled women who visited the genitourinary clinic of Taipei City Hospital‐Zhongxiao Branch between 1 February 2020 and 31 January 2021. SUI severity was classified according to the type of daily activity in which SUI occurred. Potential risk factors for SUI, including age, labor and history of hysterectomy, were also included. All participants underwent a bioelectric impedance analysis of their body composition. Independent t ‐tests and Pearson's χ ² ‐tests were used to compare the differences in continuous and categorical parameters between groups. Logistic regression analysis was used to characterize the predictive value of body composition for severe SUI. Results Of the 256 included patients, 37 had severe SUI. The participants with severe SUI were older and were more likely to have undergone a hysterectomy. They also had a considerably higher prevalence of sarcopenia. In the univariate analysis, a sarcopenia diagnosis was associated with severe SUI. Furthermore, a history of hysterectomy correlated with severe SUI, although with borderline significance. In the multivariate analysis, a history of hysterectomy and lower trunk muscle mass index were found to be independent predictors of severe SUI. Conclusions A history of hysterectomy and a lower trunk muscle mass index are correlated with severe SUI. Geriatr Gerontol Int 2025; ••: ••–•• .

Aim Autistic traits exhibit neurodiversity with varying behaviors across developmental stages. Brain complexity theory, illustrating the dynamics of neural activity, may elucidate the evolution of autistic traits over time. Our study explored the patterns of brain complexity in autistic individuals from childhood to adulthood. Methods We analyzed functional magnetic resonance imaging data from 1087 autistic participants and neurotypical controls aged 6 to 30 years within the ABIDE I (Autism Brain Imaging Data Exchange) data set. Sample entropy was calculated to measure brain complexity among 90 brain regions, utilizing an automated anatomical labeling template for voxel parcellation. Participants were grouped using sliding age windows with partial overlaps. We assessed the average brain complexity of the entire brain and brain regions for both groups across age categories. Cluster analysis was conducted using generalized association plots to identify brain regions with similar developmental complexity trajectories. Finally, the relationship between brain region complexity and autistic traits was examined. Results Autistic individuals may tend toward higher whole‐brain complexity during adolescence and lower complexity during childhood and adulthood, indicating possible distinct developmental trajectories. However, these results do not remain after Bonferroni correction. Two clusters of brain regions were identified, each with unique patterns of complexity changes over time. Correlations between brain region complexity, age, and autistic traits were also identified. Conclusion The study revealed brain complexity trajectories in autistic individuals, providing insight into the neurodiversity of autism and suggesting that age‐related changes in brain complexity could be a potential neurodevelopmental marker for the dynamic nature of autism.

Background Thyroid cancer primarily affects young women and raises concerns about future fertility due to treatments of thyroidectomy and radioactive iodine (RAI) therapy. This study investigated the effects of these treatments on pregnancy probability in young female patients post-diagnosis. Methods A nationwide, population-based study using data from Taiwan’s National Health Insurance Research Database (2000–2017) examined pregnancy likelihood in women ≤45 years with thyroid cancer. The effects of thyroidectomy and RAI therapy on pregnancy were analyzed using logistic regression and Cox proportional-hazards models. Results In a cohort of 10 937 patients with thyroid cancer, 7022 (64.2%) underwent total thyroidectomy, with 718 receiving RAI treatment. The type of thyroidectomy and RAI treatment, even at doses exceeding 120 millicuries, did not reduce the likelihood of pregnancy. Age was identified as the most critical factor influencing pregnancy; women aged >30 years had a significantly lower likelihood of becoming pregnant than younger women did. Other factors associated with a reduced likelihood of pregnancy included comorbidity with diabetes (HR = 0.65, P = .002) and higher socioeconomic status (HR = 0.69, P = .085). Conclusions Thyroidectomy and RAI therapy do not diminish pregnancy probability in young women with thyroid cancer. Age remains a crucial factor, with younger women more likely to conceive. These findings are critical for fertility counseling and treatment planning. Key message What is already known on this subjec? Thyroid cancer primarily affects young women, and its standard treatments, including thyroidectomy and radioactive iodine (RAI) therapy, have raised concerns about their potential impact on fertility. Previous studies have shown that RAI treatment may temporarily affect ovarian function but typically does not have a significant long-term effect on fertility. What this study adds? This nationwide population-based study found that neither total nor partial thyroidectomy, nor RAI treatment, adversely affects the likelihood of pregnancy in young women with thyroid cancer. Age was identified as the most significant factor influencing pregnancy, with younger women having a higher probability of becoming pregnant after treatment. How this study might affect research, practice, or policy? Clinicians should recognize that age, rather than the type of thyroidectomy or RAI treatment, is the most critical factor influencing fertility in young women with thyroid cancer. This insight can guide personalized fertility counseling and treatment planning to optimize outcomes.

OBJECTIVE This study focuses on epidermal growth factor receptor–mutated lung adenocarcinoma, known for frequent brain metastasis. It aimed to compare the clinical outcomes and cost-effectiveness of combining Gamma Knife radiosurgery (GKRS) with tyrosine kinase inhibitors (TKIs) (GKRS+TKI group) versus TKIs alone (TKI group) for the treatment of patients with newly diagnosed brain metastasis in this condition. METHODS Study characteristics of the two groups were matched using inverse probability of treatment weighting (IPTW). In the incremental cost-utility ratio (ICUR) model, a healthcare provider perspective, a 1-month cycle length, a 5-year time horizon, and a discount rate of 2% per year for both effectiveness and costs were adopted. Probabilistic and one-way sensitivity analyses were also conducted to demonstrate the robustness of the findings. Statistical analysis was performed using IBM SPSS version 23.0, and cost-effectiveness analysis was conducted using TreeAge Pro software. RESULTS After applying IPTW, the GKRS+TKI group included 205 patients, and the TKI group consisted of 102 patients, with no statistically significant differences in whole confounders. The GKRS+TKI group demonstrated significantly prolonged median progression-free survival (37.5 months vs 10.6 months, p < 0.001) and median overall survival (55.1 months vs 30.8 months, p < 0.001) compared with the TKI group. The GKRS plus TKI strategy achieved an ICUR of $30,532.25 per quality-adjusted life year relative to the TKIs at the willingness-to-pay threshold of US$33,059 (Taiwan’s per capita gross domestic product). CONCLUSIONS The use of GKRS plus TKIs not only reduces disease recurrence and improves prognosis but also demonstrates a higher level of cost-effectiveness. These findings offer valuable guidelines for clinicians and inform healthcare authorities in optimizing resource allocation for improved medical care.

Background & Aims Body composition is an objective assessment reflecting nutritional status and is highly gender different. Surgical resection, the standard treatment for early‐stage hepatocellular carcinoma (HCC), is an energy‐consuming major operation that would affect body composition. However, the impacts of body composition on the post‐operative prognosis of HCC are still uncertain. In this study, we aimed to investigate surgery‐related changes in body composition and the impacts on clinical outcomes of HCC after surgical resection distinguished by gender. Method From January 2013 to December 2018, 401 consecutive patients who received surgical resection for HCC in Taipei Veterans General Hospital were retrospectively reviewed. Cross areas of adipose and muscle mass were measured at L3 vertebral level from peri‐operative computed tomography by Slice‐O‐matic software; body composition indices were thus calculated. Factors associated with survivals were analysed. Results Body composition indices did not change significantly after surgical resection of HCC in both males and females. Higher pre‐operative intramuscular adipose tissue index (IMATI) (hazard ratio [HR]: 2.059, p = 0.002) and lower ratio of subcutaneous to visceral adipose tissue index (SATI/VATI) (HR: 1.681, p = 0.028) were independent predictors of worse overall survival (OS) in male patients. In females, higher pre‐operative IMATI (HR: 3.053, p = 0.001) was the only body composition‐related factor predicting OS. Conclusion Surgical resection contributed minor changes in body composition in patients with early HCC. Myosteatosis and subcutaneous to visceral fat ratio were survival predictors in male patients, but myosteatosis was the only body composition‐predictor of survival in females.

Background Early detection is crucial for the timely intervention and management of dementia, potentially slowing its progression. Early stages of dementia might only subtly affect communication, yet connected speech analysis can detect these minor anomalies. Cognitive tests involving connected speech, like the Boston Diagnostic Aphasia Examination’s (BDAE) “cookie‐theft” picture description task, are pivotal in detecting dementia. However, previous research typically treats their responses as a whole. Method This study preprocesses connected speech from the “cookie theft” task to facilitate AI‐driven detection improvements. We analyzed narratives from 54 normal subjects, 26 with MCI, and 38 with Alzheimer’s Disease (AD), focusing on nine major concepts to quantify accuracy across groups. Result Differences in concept accuracy were significant even among normal individuals. A detailed analysis revealed that concepts 3 and 1 were particularly effective in differentiating between normal individuals and those with cognitive impairments, and between MCI and AD. Concepts 2, 3, and 7 were crucial for distinguishing between normal and MCI subjects. Concepts 4, 5, 8, and 9 showed no discriminatory power. Conclusion Advances in technology, particularly in natural language processing (NLP), allow for the automated analysis of connected speech. It can provide quick and reliable assessments. By categorizing and preprocessing speech data before AI analysis, our approach enhances the model’s predictive accuracy for early‐stage dementia detection. It can also help for developing more diagnostic images and cognitive training exercises. Furthermore, it does not require expensive equipment or invasive procedures, making it accessible for widespread use in various settings, including community centers and primary care, and particularly beneficial for regular monitoring.

Background Previous systemic reviews, predominantly including observational studies, have shown that participation in social activities is a protective factor against cognitive decline. However, this association is subject to potential reverse causality, creating a knowledge gap in our understanding of the effect of social interaction interventions on cognitive function. Therefore, this study aims to conduct a systematic review and meta‐analysis of randomized‐controlled trials to examine the effects of social interaction interventions on cognitive decline among non‐demented older adults. Method This systematic review was registered in PROSPERO (CRD42022367828), and we systematically searched six databases from inception to May 6, 2022, to identify relevant articles on the effects of activities with social interaction components on cognitive function in community‐dwelling non‐demented older adults over 60. Two independent reviewers performed study selection, data extraction, and bias assessment, and RevMan5.3 was used to conduct the meta‐analysis. Subgroup analysis was conducted to explore potential sources of heterogeneity and assess variation in intervention effects across subgroups. Result We included 11 studies for qualitative analysis and eight studies for the meta‐analysis. The result showed that social interaction intervention had a significant effect on executive function (SMD = 1.63; 95% CI, 0.55 to 2.70), but not attention (SMD = 0.09; 95% CI, ‐0.09 to 0.26) and memory (SMD = ‐0.03; 95% CI, ‐0.32 to 0.25). The subgroup analysis showed a greater cognitive benefit among normal older adults but not older adults with mild cognitive impairment. Additionally, when considering different social interaction modes, in‐person social interaction positively affected global cognition, while online interaction did not. Conclusion Social interaction interventions have a limited impact on cognitive function in non‐demented older adults but showed potential effects on executive function. This finding offers insights for implementing social intervention in the community. Future efforts should focus on conducting more rigorous clinical trials to investigate the effects of different types of social interaction interventions on specific cognitive domains.