Clinical Interventions in Aging最新文献

Purpose: Postoperative delirium affects up to 65% of elderly surgical patients, leading to increased mortality and cognitive decline. Current prevention strategies face implementation barriers, necessitating accessible, non-pharmacological interventions. Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive neuromodulation technique, reduces neuroinflammation and regulates autonomic function, offering potential for delirium prevention. This multicenter, randomized, double-blind, sham-controlled trial evaluates whether taVNS can prevent postoperative delirium in older adults undergoing total knee arthroplasty.

Patients and methods: We will enroll 1448 patients aged 65-80 years undergoing elective knee replacement under general anesthesia at four hospitals in Fujian Province, China. Participants will be randomized equally to receive active taVNS (25 Hz, 250 μs targeting the cymba conchae and tragus) or sham stimulation (25 Hz, 250 μs targeting the earlobe and antihelix). Both groups will receive interventions at two timepoints: the afternoon before surgery and the morning of surgery before anesthesia. The primary outcome is delirium incidence within 72 hours postoperatively, assessed using the Confusion Assessment Method. Secondary outcomes include inflammatory markers (interleukin-1, interleukin-6, tumor necrosis factor-alpha), autonomic function (heart rate variability), cognitive trajectories, psychological status, sleep quality, pain scores, and recovery parameters. Safety monitoring will follow standardized adverse event reporting guidelines.

Conclusion: If effective, taVNS could provide a practical, non-invasive method to reduce delirium incidence in elderly patients undergoing knee replacement, potentially improving postoperative outcomes and reducing healthcare costs.

Purpose: Perioperative neurocognitive disorder (PND) is common in elderly surgical patients and severely affects postoperative recovery. However, effective prevention is still lacking. Potential perioperative cerebral stressors (including inappropriate sedative/analgesic depth and imbalanced cerebral oxygen supply/demand) may be important contributing factors. We developed an anesthesia management protocol based on multimodal brain monitoring to achieve standardized, individualized, and real-time regulation of sedative/analgesic depth and cerebral oxygen saturation and investigated whether it could reduce the incidence of PND and its underlying mechanisms.

Patients and methods: Patients (aged ≥65 years) were randomized into Groups C (n=88) and E (n=93). Patients in Group E received multimodal brain monitoring-guided anesthesia management, and those in Group C received BIS-guided anesthesia management. The Montreal Cognitive Assessment (MoCA) was performed both before and seven days after surgery. The postoperative pain scores were recorded. Resting-state functional MRI data were analyzed to examine functional connectivity (FC).

Results: Group E demonstrated a numerically lower incidence of PND (15.50% vs 21.59% in Group C), but this difference was not statistically significant. Patients in Group E had increased FC within the right pulvinar, right sub-gyral region, and right inferior parietal lobule (P < 0.05). Significantly lower pain scores were observed in Group E at rest (1h: P=0.04; 24h: P=0.04) and during movement (1h: P=0.03).

Conclusion: These results suggest that multimodal brain monitoring-guided anesthesia management may protect neurocognition by enhancing FC within cognition-associated brain regions and attenuating postoperative acute pain. And multimodal brain monitoring-guided anesthesia management may confer a clinically relevant reduction in PND incidence compared to BIS-guided management in elderly surgical patients.

Background: Frailty is a common geriatric syndrome, and its occurrence in elderly stroke patients may further worsen clinical outcomes, yet the influencing factors and potential causal relationship remain unclear.

Objective: This study aimed to identify the influencing factors of frailty in elderly hospitalized stroke patients and to analyze the potential causal relationship between stroke and frailty.

Methods: A multicenter cross-sectional survey including 210 elderly stroke patients was conducted, and bidirectional Mendelian randomization analysis was applied to examine the causal relationship between stroke and frailty. Univariate and multivariate logistic regression analyses were used to explore the impact of physiological, psychological, and clinical symptom factors on frailty.

Results: The frailty index was positively correlated with stroke, and Mendelian randomization confirmed a bidirectional causal relationship. Univariate analysis showed significant associations between frailty and diabetes, lesion site, lesion location, and brain atrophy. Multivariate logistic regression further identified Fugl-Meyer score, Berg score, and MoCA score as independent risk factors for frailty in elderly hospitalized stroke patients.

Conclusion: Frailty is strongly associated with stroke, and elderly stroke patients face an increased risk of frailty during hospitalization. These findings provide a basis for early identification of high-risk patients and the development of targeted intervention strategies in clinical practice, with important implications for stroke rehabilitation and elderly care.

Aging is a complex, multifactorial process driven by interconnected biological mechanisms collectively known as the hallmarks of aging, which contribute to functional decline and the onset of age-related diseases. High-mobility group box 1 (HMGB1), a nuclear DNA chaperone and damage-associated molecular pattern (DAMP), plays a pivotal role in regulating these hallmarks through its dual functions: preserving genomic stability within the nucleus and promoting inflammatory responses when released extracellularly. This review examines the multifaceted involvement of HMGB1 in key aging hallmarks, such as genomic instability, telomere attrition, mitochondrial dysfunction, and chronic inflammation among others. Preclinical studies demonstrate that nuclear HMGB1 supports chromatin integrity and DNA repair, whereas its extracellular release triggers TLR4/RAGE signaling pathways, thereby intensifying inflammaging and senescence-associated secretory phenotypes (SASP). Emerging therapeutic approaches-such as HMGB1 inhibitors, neutralizing antibodies, and epigenetic modulators-show potential in restoring genomic homeostasis and mitigating age-related pathologies. Nevertheless, significant challenges remain, including elucidating HMGB1's roles in nutrient sensing and psychosocial stress, fine-tuning interventions to preserve its nuclear functions while minimizing extracellular toxicity, and establishing efficacy in human clinical settings. Addressing these gaps may position HMGB1 as a promising multifunctional target for delaying aging and translating preclinical findings into clinical applications.

Semantic dementia (SD) is a progressive neurodegenerative disorder primarily characterized by core linguistic deficits, notably impaired confrontation naming and single-word comprehension. Associated features include surface dyslexia, prosopagnosia, relatively preserved speech production, and emotional or behavioral abnormalities. Neuroimaging reveals initial asymmetrical atrophy of the anterior temporal pole, with subsequent progression posteriorly and contralaterally. Early detection is challenging due to initial presentation often manifesting as mild word-finding difficulties, furthermore, comorbid behavioral-emotional symptoms and distinct clinical profiles associated with right- versus left-sided atrophy complicate diagnosis. Therefore, this paper comprehensively delineates the principal clinical features of SD, encompassing language deficits, emotional impairment, behavioral disturbances, and other domains. It also reviews structural and functional imaging findings and investigates the relationship between clinical manifestations and patterns of brain injury. To advance understanding of SD's clinical manifestation, the paper introduces the controlled semantic and social-semantic frameworks.

Phytoestrogens (PEs), a class of naturally occurring plant compounds primarily categorized into isoflavones, lignans, flavonoids, coumarins, and stilbenes, exhibit structural similarity to endogenous estrogens and exert regulatory effects through estrogen receptors. This comprehensive review examines the multifaceted roles of PEs in enhancing exercise performance and promoting health among postmenopausal women. Current evidence demonstrates that PEs not only ameliorate characteristic menopausal symptoms but, more significantly, improve physical function through multiple mechanisms: (1) augmenting muscle protein synthesis while mitigating inflammation and oxidative stress to optimize muscular performance; (2) modulating glucolipid metabolism and cardiovascular function to establish physiological foundations for exercise; and (3) preserving bone mineral density and regulating neurotransmitter activity to maintain motor coordination. Although combined PE-exercise interventions demonstrate synergistic benefits, their efficacy is influenced by dosage variations and interindividual metabolic differences. Future investigations should prioritize the development of precision PE applications to optimize kinesiological outcomes and health parameters in postmenopausal populations.

Purpose: Sarcopenia (SP) and osteoporosis (OP) both pose higher risks for adverse health outcomes. This study explored the relationship among sarcopenia, osteoporosis and all-cause mortality.

Patients and methods: This retrospective cohort utilized a tertiary-hospital-based cohort during the years from 2018 to 2024. Patients received dual-energy X-ray absorptiometry scans. Osteoporosis was diagnosed when T-scores of <-2.5 were determined at the L-spine or femoral neck. Sarcopenia was defined using the Asian Working Group for Sarcopenia 2019 criteria: low muscle strength, low physical performance, and a low appendicular skeletal mass index. We utilized the Cox proportional hazard model and Kaplan-Meier curves to depict observed time to mortality. Post-hoc analysis was applied for subgroup comparison and statistical power calculation. Interaction terms sensitivity analysis was used for analyzing mutually exclusive groups.

Results: A total of 545 patients (median age [interquartile range] 68.7 [52.8-80.7] years; 72.3% women) were analyzed. At baseline, 15.6% had SP alone, 23.1% had OP alone, and 14.3% had both conditions. Over median 0.7 (interquartile range = 0.2-1.4) years of follow-up, 24 deaths occurred. Older age, multimorbidity, sarcopenia, and osteoporosis were significantly associated with higher mortality. In multivariable analysis adjusting for age and multimorbidity, sarcopenia alone was a stronger predictor of mortality compared to osteoporosis alone (hazard ratio [HR] 7.34 vs 3.99), and the mortality HR was 7.34 for sarcopenia with or without osteoporosis higher than 3.99 for osteoporosis with/without sarcopenia. Interaction analysis was not feasible in the four-group comparison, as the interaction term overlapped with the 'both sarcopenia and osteoporosis' group; in the other three groups, the SP×OP interaction was not significant. SP patients were more likely to be older, male, and have lower body mass index, total tissue, and lean mass.

Conclusion: These findings suggest that sarcopenia may be a more important predictor of mortality than osteoporosis in patients, highlighting the need for muscle health assessment.