The journals of gerontology. Series A, Biological sciences and medical sciences最新文献

Background: Serum uric acid (SUA) has been linked to cognitive function, but sex-specific associations remain unclear. Biological differences in SUA levels between sexes, driven by hormonal and renal factors, highlight the importance of sex-stratified analysis. This study examined the association between SUA levels and changes in cognitive function in older adults.

Methods: A total of 11 411 community-dwelling ASPirin in Reducing Events in the Elderly participants, free from dementia at baseline and with valid SUA measurements, were included. The Modified Mini-Mental State Examination (3MS), Hopkins Verbal Learning Test-Revised (HVLT-R), Symbol Digit Modalities Test, and Controlled Oral Word Association Test were used to assess cognition at baseline and over a median follow-up of 9 years. Separate linear mixed-effects regression models in males and females were fitted to assess the associations between SUA levels and change in cognitive function over time.

Results: Females in the lowest SUA quintile (Q1) had significant declines in the measure of global cognition (3MS: β ±SE= -0.07 ± 0.03, p = .02) and episodic memory (HVLT-R; delayed recall: β±SE= -0.03 ± 0.01, p = .02) compared to the middle quintiles (Q2-Q4), but the highest SUA quintile (Q5) was not associated with decline. No associations were observed for executive function, verbal fluency, or psychomotor speed. In males, no significant associations between SUA levels and change in cognitive function were observed.

Conclusion: Low SUA levels were linked to decline in the measure of global cognition and episodic memory among females but not males. High SUA levels were not associated with cognitive decline. Managing SUA levels within the physiological range may support cognitive health, particularly in older females.

Background: The impact of exposure to fine particulate matter (PM2.5) on post-discharge recovery in older adults already hospitalized for heart failure remains unclear. We evaluated associations between exposure to PM2.5 and days spent at home (DAH) as well as mortality in a nationwide representative sample of U.S. adults aged 65 years and older.

Methods: Data from 66 854 Medicare Fee-for-service beneficiaries with heart failure hospitalization (2017-2019) were linked with validated, model-derived mean PM2.5 concentrations at Zip Code Tabulation Areas level during the month of hospital admission. Post-discharge 180-day DAH was defined as days alive minus days spent in inpatient hospitals, hospital observation units, nursing facilities, or emergency departments. All-cause mortality was assessed as time from hospital discharge to death within 180 days. Quantile regression and Cox proportional regression models, adjusted for covariates, were used to quantify associations.

Results: Exposure to the highest quartile PM2.5 level (>8.61 µg/m3) was associated with 5.05 fewer DAH (95% CI: -8.61, -1.48; P = 0.006) after discharge at the 20th percentile of DAH, compared with those exposed to the lowest PM2.5 quartile ( < =5.90 µg/m3). Exposure to the highest quartile PM2.5 levels was also associated with higher risk of all-cause mortality within 180 days after hospitalization as compared to the lowest PM2.5 quartile (hazard ratio = 1.05 (95%CI: 1.004-1.10, P = 0.033).

Conclusions: Particulate air pollution may negatively impact recovery more strongly at the lower tail of recovery than at the median or higher tail, highlighting the need for targeted intervention strategies to protect the most vulnerable patients.

Background: This study examined whether physical activity (PA) buffers air-pollution-related cognitive decline in middle-aged and older adults, quantified the dose-response relationship, and derived pollution-specific PA recommendations.

Methods: Data came from 5 waves (2011-2020) of the China Health and Retirement Longitudinal Study, including 12 196 adults aged ≥45 years. Ambient pollutants were estimated using a high-resolution satellite-based model. Linear mixed-effects models assessed main and interactive effects of PM2.5, PA, and PA × PM2.5 on cognition, stratified by socioeconomic status (SES) and residential setting. Isotemporal substitution and generalized additive models evaluated risk-benefit trade-offs and non-linearities. PA prescriptions were calculated using (PM2.5-25) × 1.316, with values ≤0 set to 0.

Results: Higher PM2.5 exposure predicted poorer cognition (β = -.0146, p < .001). PA buffered this effect (interaction β = .0344, p = .001), consistent across SES and residence. Among PM2.5 constituents, sulfate (β = -.0136) and black carbon (BC) (β = -.1059) were harmful. Vigorous PA neutralized the BC effect, while light-to-moderate PA offset the sulfate effect. Isotemporal substitution showed that 13.16 min/day of PA offset the cognitive impact of a 10 µg/m³ increase in PM2.5. Region-specific estimates required 10.92 min/day in Beijing and 4.01 in Shanghai, while Guangdong and Fujian required none.

Conclusions: Sulfate and BC are key drivers of PM2.5-related cognitive decline. Roughly 13 min of daily PA neutralizes the effect of each 10 µg/m³ PM2.5 rise. Light-to-moderate PA is preferable in sulfate-dominated areas, while vigorous PA is more effective in BC-dominated regions.

Alzheimer's disease (AD) develops gradually, with significant neurodegeneration already present by the time clinical symptoms emerge. Since synapses are affected early in the disease, synaptic proteins are being investigated as potential markers of the prodromal stage. Using data and plasma samples provided by the Consortium for the early identification of Alzheimer's disease-Quebec (CIMA-Q), we analyzed plasma levels of neuroligin (NLGN)-derived peptides in cognitively normal (CN) individuals and cognitively impaired (CI) individuals, including those with amnestic mild cognitive impairment (aMCI) and early-stage Alzheimer's disease (AD). Plasma levels of NLGN-derived peptides were assessed by quantifying tryptic peptides using liquid chromatography coupled with tandem mass spectrometry. Our findings show that levels of specific NLGN peptides were significantly elevated in CI compared to CN individuals. Receiver operating characteristic (ROC) curve analysis revealed that some NLGN peptides could distinguish CI individuals. Furthermore, analysis based on Mini-Mental State Examination (MMSE) scores revealed that specific plasma phosphorylated tau peptides were significantly and positively correlated with selected NLGN-derived peptides in more advanced stages of cognitive decline. These results support further investigation into synaptic NLGN-derived peptides in the blood as promising tools for monitoring the earliest stages of AD.

Background: Aging alters oral structures, affecting chewing and swallowing function. Oral function is increasingly recognized as an important component of systemic health outcomes in older individuals. Understanding age-related changes in oral function is crucial for oral health care. This study comprehensively evaluated the various oral function determinants and their age-related changes, identified key factors, and estimated the prevalence of people with poor oral function.

Methods: A cross-sectional study of older individuals (n = 206) participated. Oral functions were objectively assessed through dental status, saliva secretion, orofacial muscle strength, masticatory performance, and swallowing function. Correlation analysis, cluster analysis, and multiple regression were employed to explore the complexities of oral function determinants and their interrelationships and to estimate the prevalence of individuals with poor oral function.

Results: Correlation analysis showed significantly (p < 0.001) strong (rs = -0.79) to low (rs = -0.11) correlations between determinants of oral function. The cluster analysis successfully identified three major groups of oral function. Further, the multiple linear regression and backward elimination showed that chewing strokes, natural teeth, and tongue pressure (p < 0.001) were significant predictors of age. Additionally, the prevalence of older individuals with poor dental status, reduced tongue pressure strength, and low saliva secretion rate was estimated at 9.7%, 14.6%, and 8.3%, respectively.

Conclusions: Oral function determinants reflect age-related change and have the potential to estimate the prevalence of older people with poor oral function. These findings may be critical in identifying the phenotypic profile of people with poor oral function.

There is growing interest in whether adult vaccines such as shingles vaccine may slow biological aging beyond preventing acute infections. Using data from the nationally representative U.S. Health and Retirement Study, we examined whether shingles vaccination is associated with more favorable profiles across seven biological aging domains: inflammation, innate and adaptive immunity, cardiovascular hemodynamics, neurodegeneration, and epigenetic and transcriptomic aging, as well as a composite biological aging score. Analyses included adults aged 70+ in 2016 (n = 3,884), with biological measures drawn from venous blood, flow cytometry, and physical assessments. Weighted linear regressions adjusted for sociodemographic, and health covariates. Shingles vaccination was significantly associated with lower inflammation scores (b=-0.14, p = 0.0027), slower epigenetic (b=-0.17, p = 0.0001) and transcriptomic aging (b=-0.19, p < .0001), and a lower composite biological aging score (b=-0.18, p = 0.0002), suggesting potential benefits for systemic inflammation, molecular and overall biological aging. In contrast, vaccination was linked to higher adaptive immunity scores (b = 0.09, p = 0.0133), an unexpected finding warranting further investigation. Timing analyses indicated that epigenetic, transcriptomic and overall composite biological aging improvements were most pronounced within three years post-vaccination, with slower aging persisting beyond this window. The results support the hypothesis that shingles vaccination may influence key biological systems relevant to aging, though effects appear domain-specific and vary over time. Longitudinal studies are needed to confirm these patterns and explore implications for long-term health. This study adds to emerging evidence that vaccines could play a role in strategies to promote healthy aging by modulating biological systems beyond infection prevention.

Vascular dementia (VaD) is a leading cause of cognitive decline, yet its underlying molecular mechanisms remain incompletely understood. This study aims to investigate the alterations associated with VaD in neuronal and endothelial cells by integrating single-nucleus RNA sequencing (snRNA-seq) with microarray data from postmortem VaD brain tissues. Using high-dimensional weighted gene co-expression network analysis (hdWGCNA) and machine learning approaches, we identified SOX6 in neurons and LDLRAD3 in endothelial cells as key factors associated with VaD pathology. Functional enrichment analyses revealed that glutamatergic synapses and MAPK signaling are critical pathways in neurons, while the MAPK signaling pathway, lipid metabolism, and atherosclerosis in endothelial cells contribute to VaD progression. In a mouse model of post-stroke cognitive impairment induced by transient middle cerebral artery occlusion, SOX6 and LDLRAD3 were significantly upregulated at both the mRNA and protein levels, supporting their roles in VaD. These findings provide novel insights into potential therapeutic targets for VaD and highlight the importance of endothelial and neuronal interactions in disease progression.

Background: Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by progressive memory decline. The increasing prevalence of AD has attracted considerable attention globally. The glucagon-like peptide-1 analog, liraglutide, a drug widely used in the treatment of type 2 diabetes, has shown promising neuroprotective effects in AD, including enhancing neuronal survival, reducing amyloid beta protein accumulation, improving synaptic plasticity, and reducing tau protein hyperphosphorylation. However, its potential impact on cognitive function remains unclear.

Methods: We evaluated the effects of liraglutide (25 nmol/day for 8 weeks) on the cognitive ability of 12-month-old 5 × familial AD (FAD) mice. The Morris water maze test was used to evaluate the spatial learning ability of mice. Histological evaluations were performed by Nissl staining and transmission electron microscopy. Neuroinflammation was detected by double immunofluorescence staining and enzyme-linked immunosorbent assay. Protein expression in the cortex and hippocampus was detected by immunohistochemistry and Western blotting.

Results: The spatial cognitive ability improved in 5 × FAD mice after liraglutide administration and was associated with an increased number of pyramidal cells in the cortex and hippocampus. Liraglutide also alleviated ultrastructural changes in the chemical synapses and reduced both local and systemic inflammation in AD mice. Furthermore, liraglutide reduced amyloid β protein expression, which may be associated with the regulation of nuclear factor kappa B/beta-secretase 1 pathways in AD mice.

Conclusions: The potential of liraglutide to improve cognitive function in AD mice offers an effective pharmacological approach for treating neurodegenerative diseases.