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

Background: Characterizing the correlates of adult mortality can lend insights into the factors associated with consequential health outcomes among older adults. In India, the importance of adult mortality has grown given trends in population aging, but prior research has been limited by a lack of high-quality longitudinal data.

Methods: We used new data from Waves 1 (2017-2019) and 2 (2022-2024) of the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD) study (N = 3,871) to evaluate associations between all-cause mortality and 27 socioeconomic and clinical factors using Cox proportional hazards models. We also evaluated gender differences and the impact of COVID-19.

Results: The estimated mortality rate was 6.0 (95% CI 5.6-6.4) deaths per 100 person-years. A broad range of factors were associated with mortality, but cardiometabolic and cognitive phenotypes had some of the strongest associations; those with dementia had a 2.84 (95% CI 2.12-3.81) times greater risk of death than those with normal cognitive functioning. Associations with socioeconomic factors tended to be stronger for men than women (e.g., wealth quintile; χ2 p = 0.046), whereas associations with clinical factors tended to be stronger for women than men (e.g., diabetes; χ2 p = 0.033). We observed some evidence of excess mortality due to COVID-19.

Conclusion: Findings emphasize the multifaceted nature of health among older adults in India and illustrate the need for solutions that recognize the importance of a wide range of social factors and clinical health conditions. Results also showcase the importance of dementia as a key factor associated with survival among older adults.

The cerebellum, traditionally recognized for motor coordination, may also contribute to cognitive and emotional regulation, as recent evidence indicates. However, the molecular and structural changes in the human cerebellum during healthy aging remain poorly understood. This study systematically investigated the molecular trajectories and structural alterations in the human cerebellum across the adult lifespan (20-80 years) by integrating cerebella transcriptomic data from 456 non-disease brains and MRI structural neuroimaging data from 264 disease-free subjects. Fuzzy clustering analyses uncovered nonlinear expression trajectories involving synaptic plasticity, metabolic regulation, and protein homeostasis, highlighting multiple critical biological turning points across different age periods. Differential gene expression analyses identified early downregulation of immediate early genes (e.g., FOS, NPAS4, EGR1-3) and sustained activation of stress-response pathways changes that precede observable functional decline. Moreover, we identified an integrated "synaptic plasticity-stress homeostasis" module, where IEGs and heat shock proteins exhibit coordinated regulation whose efficiency progressively declines with age. MRI analyses showed a pronounced acceleration of cerebellar gray matter loss after age 70, with multiple subregions affected, highlighting the nonlinear trajectory of cerebellar structural aging. In combination with the transcriptomic findings, these results indicate that cerebellar aging comprises complex, stage dependent molecular alterations accompanied by gray matter reductions in later decades. This collective evidence advances our understanding of cerebellar aging biology and highlights the synaptic-stress module as a promising molecular axis that may inform future strategies to support cerebellar function in older adults.

Background: Adverse childhood experiences (ACEs) have detrimental health effects later in life. Our objective was to assess the association between ACEs and falls among middle-aged and older adults in the United States.

Methods: We used data from 38 437 participants aged 45 to 80 years from the 2023 Behavioral Risk Factor Surveillance System. The outcome was falling during the past 12 months. Adverse childhood experiences included questions about events before age 18, and 2 main domains of abuse (5 questions) and household dysfunction (6 questions), with a total score of 0 to 11, dichotomized as ≥2 ACEs versus 0-1. We assessed the association between ACEs and falling and explored whether risk factors for falling mediate the association between ACEs and falling.

Results: Among middle-aged adults (45-64 years), 22.3% had fallen, and 46.4% had ≥2 ACEs. Among older adults (≥65), 27.7% had fallen, and 31.7% had ≥2 ACEs. In multivariate analyses, participants with ≥2 ACEs have increased odds of falling compared to those with 0-1 ACEs among middle-aged (odds ratio [OR] = 1.34) and older adult participants (OR = 1.28). Even one individual ACE question, such as living with anyone who served in prison (among 45-64; OR = 1.43) or being sexually touched (among ≥65; OR = 1.45), has an independent association with falling. People with depression, functional difficulties, multimorbidity, and difficulty remembering exhibited higher proportions (%) for mediation.

Conclusions: Adverse childhood experiences are an additional risk factor for falling among middle-aged and older adults in the United States. Clinicians and public health practitioners should also consider ACEs when exploring determinants for falling across the life course.

Background: While associations between poor oral health and cognitive impairment are documented, research on how different oral health conditions relate to specific cognitive measures remains limited.

Methods: Using data from 756 Baltimore Longitudinal Study of Aging 2005-2024 participants (mean age = 72.0 years, 52.5% women, 24.2% Black), we investigated the association between the first oral health assessment and subsequent cognitive decline across domains in older adults aged 60+ who were free of cognitive impairment at baseline over an average of 7.7 follow-up. Cognitive function was assessed across language, executive function, attention, memory, and visuospatial ability domains, with domain-specific composite scores calculated using various cognitive tests. Oral health was evaluated for clinically-assessed tooth loss and dental plaque, alongside self-reported periodontal symptoms. Linear mixed-effect models were used to examine the longitudinal associations with cognitive decline, adjusted for socio-demographic and clinical characteristics.

Results: After covariates adjustment, more tooth loss was associated with greater declines across all cognitive domains, including language (β = -0.0017; 95% CI = -0.0025, -0.0008), executive function (β = -0.0011; 95% CI = -0.0019, -0.0002), attention (β = -0.0011; 95% CI = -0.0021, -0.0001), memory (β = -0.0018; 95% CI = -0.0030, -0.0005), and visuospatial ability (β = -0.0017; 95% CI = -0.0029, -0.0006). Dental plaque was associated with executive function (β = -0.0165; 95% CI = -0.0276, -0.0054) and memory (β = -0.0279; 95% CI = -0.0444, -0.0115) declines. Presence of periodontal symptoms was only associated with executive function decline (β = -0.0004; 95% CI = -0.0007, -0.0001).

Conclusions: Tooth loss may indicate broader cognitive decline, while other oral health conditions, such as plaque and periodontal symptoms, particularly affect memory or executive function. Future studies are warranted to investigate underlying mechanisms.

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.

Background: Social isolation is a key social determinant of health, yet research on its relationship with functional impairment is limited. We compared functional impairment score trajectories of older adults who experienced social isolation versus those who did not, using two different statistical approaches to handle attrition due to dropout and death.

Methods: Data were from two Northern California observational cohorts of people aged 50 + (n = 2,476): Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) and Study of Healthy Aging in African Americans (STAR). We fit linear mixed effects models for functional impairment scores [sum of 12 items measuring basic activities of daily living (ADLs), instrumental ADLs, and mobility; range: 0-36] by baseline social isolation status (yes/no; 3-5 positive answers on 5 social contact items), adjusted for age and sex/gender. We estimated average marginal wave-specific differences in functional impairment scores, comparing approaches to address attrition.

Results: At baseline, 30% of participants reported social isolation; median functional impairment score was 2 (Q1, Q3 = 0, 5). Baseline functional impairment scores were 1.03 points (95% CI: 0.84, 1.20) higher among participants experiencing social isolation versus not. At Wave 4, this difference decreased to 0.80 (95% CI: 0.52, 1.07) among those remaining in the study and increased to 1.16 (95% CI: 0.83, 1.42) assuming attrition was eliminated. Dropout and death were higher among participants experiencing social isolation.

Conclusion: In a diverse cohort of older adults, those experiencing social isolation tend to experience greater functional impairment, but differences in trajectories depend on how attrition is handled.