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

Background: This study aimed to investigate whether depressive symptoms mediate the association between cumulative loneliness and memory function during aging.

Methods: Data were from 4779 adults aged over 50 in the U.S. Health and Retirement Study in two random sub-cohorts from 2006 to 2018 (Cohort A) and 2008 to 2020 (Cohort B). Participants were categorized as experiencing loneliness at 0, 1, 2, or 3 time points over an 8-year exposure period according to the UCLA Loneliness Scale. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale. Episodic memory function was assessed at the follow-up by immediate and delayed word recall scores. Causal mediation analysis was performed in the pooled cohorts.

Results: Mean baseline age (SD) was 65 (7.6), and 62% of the sample was female (2941/4779). Greater cumulative loneliness over the 8-year exposure period was associated with lower subsequent memory function in a dose-response relationship. Observed estimates for loneliness at each of 1, 2, and 3 time points were comparable in magnitude to an additional 0.26, 0.84, and 2.56 years of aging-related memory decline, respectively. The proportion of the association mediated by depressive symptoms decreased from 70% to 21% as the duration of loneliness increased.

Discussion: Depressive symptoms may be a psychological mechanism through which cumulative loneliness negatively affects memory function among middle-aged and older adults in the USA.

Background: This study will identify cortical proteins that may provide motor resilience, the capacity to maintain motor function despite underlying Alzheimer's disease and related dementias (ADRD) pathologies.

Methods: We studied 850 decedents with postmortem indices of 10 ADRD pathologies and proteome from dorsal lateral prefrontal cortex. Annual parkinsonian signs were assessed using a modified Unified Parkinson Disease Rating Scale. First, we adjusted linear models for ADRD pathologies to isolate resilience proteins, unrelated to ADRD pathologies, but that were related to linear motor decline. Next, functional mixed effects (FMEs) models were used to determine if resilience proteins were related to non-linear motor decline. Exploratory functional enrichment was then used to assess pathways underlying motor resilience proteins.

Results: Mean age at death was 90 years (SD = 6.4), 69% female and 7 years follow-up. Adjusting linear models for age, sex, and ADRD pathologies, we isolated thirteen proteins that may provide motor resilience (Bonferroni correction p < 5 × 10-6). FME models showed, that on average, progression of parkinsonian signs was non-linear from 25 to 12 years before death, followed by accelerated linear decline until death. Five of thirteen resilience proteins were also related to non-linear decline. Motor resilience may be supported by a coordinated network of proteins that help to preserve neuronal structure, cellular transport, and synaptic integrity, functions critical for diverse aging phenotypes.

Conclusions: Cortical proteins may provide motor resilience for both linear and non-linear motor decline. Further drug discovery targeting resilience proteins may yield therapies that can reduce motor impairment even in the absence of treatments for ADRD pathologies.

Background: Cognitive decline is a major public health challenge in aging populations, closely linked to cerebral blood flow (CBF) reductions. While exercise is suggested to improve cognitive function and cerebrovascular health, its precise effects remain unclear.

Methods: A systematic review and meta-analysis were conducted on studies published up to January 2024 using PubMed, Web of Science, ScienceDirect, Embase, Cochrane, PsycINFO, ClinicalTrials.gov. A total of 57 studies on cognitive function and 12 on CBF were included, focusing on randomized controlled trials (RCTs) or controlled trials. Standardized mean differences (SMDs) and weighted mean differences (WMDs) were calculated using fixed- or random-effects models. Regression analysis examined the association between CBF and cognitive outcomes.

Results: Exercise interventions significantly improved cognitive function (SMD = 0.52, 95% CI [0.31, 0.74], P < .001), particularly in inhibitory control, switching function, memory, and verbal fluency. Additionally, exercise increased middle cerebral artery velocity (WMD = 1.88, 95% CI [0.08, 3.67], P < .05) while reducing resting heart rate and pulse index. Higher CBF was positively correlated with cognitive performance, particularly memory and verbal fluency.

Conclusion: Exercise enhances cognitive function in older adults by improving macrovascular CBF and cardiovascular efficiency. The positive effects of exercise on macrovascular CBF, as demonstrated by increased MCAv and reduced PI, play a crucial role in promoting cognitive health in the elderly. These findings support structured exercise programs as a non-pharmacological intervention for promoting brain health and delaying cognitive decline.

Exercise is one of the most promising anti-aging interventions for maintaining skeletal muscle health in older adults. Nine "Aging Hallmarks," proposed by López-Otín, offer insights into the aging process; however, the link between these hallmarks and exercise is not fully elucidated. In this study, we conducted a systematic multi-omics analysis of skeletal muscles, focusing on aging and exercise, based on gene signatures for aging hallmarks. It is posited that mRNA splicing activity, linked to genomic instability, constitutes a fundamental hallmark of aging, and exhibits divergent expression patterns in response to aging and exercise. Additionally, we analyzed splicing events and discovered that intron retention (IR) is significantly impacted by aging, exhibiting contrasting changes to those induced by resistance training in the older cohort. The isoforms characterized by IR are notably enriched in mitochondrial functions. Conclusively, our results underscore the significance of splicing mechanisms as a novel aspect of aging hallmarks in skeletal muscles and propose a new mechanism by which exercise exerts its anti-aging effects on skeletal muscles through IR.

Axenic dietary restriction (ADR) represents a powerful and unique DR regimen for Caenorhabditis elegans as it robustly extends lifespan independently of well-known key genes associated with DR, such as those of insulin/IGF-1 signaling, skn-1, and pha-4. Here, we analyze C. elegans survival in a dilution series of axenic medium to explore the dependency of lifespan extension on nutrient availability. We find a non-linear relationship between lifespan and axenic nutrient levels with a four-fold axenic dilution yielding peak longevity. Notably, lifespan extension at specific dilutions permits maintenance of reproductive potential and survivability after bacterial reintroduction, indicating a partial reliance on adult reproductive diapause mechanisms. Genetic analyses found the involvement of AMPK/aak-2, sir-2.1, and cbp-1 in mediating lifespan extension across the axenic dilution spectrum, the essential role of daf-16 and hlh-30 under severe nutrient scarcity, and the specific contribution of bli-4 to standard ADR longevity. These findings elucidate that C. elegans lifespan extension under different levels of nutrient restriction is governed by overlapping yet distinct genetic pathways.

Background: Little is known about how psychosocial factors and geriatric conditions contribute to persistent post-COVID symptoms among older adults. We evaluated symptom burden following COVID-19 hospitalization and identified risk factors for persistent symptoms among -community-dwelling older adults.

Methods: This prospective study recruited 281 older persons (mean age 70.6 years) hospitalized for SARS-CoV-2 infection between June 2020 and June 2021 from Yale-New Haven Health System. Post-COVID symptoms were assessed using a modified Edmonton Symptom Assessment System during hospitalization, and at 1, 3, and 6 months post-discharge. Trajectory analysis identified three symptom trajectories. Multinomial logistic regression evaluated associations between characteristics (sociodemographic, clinical, psychosocial factors, and geriatric conditions) obtained during hospitalization and trajectory membership.

Results: Three symptom burden trajectory groups were identified: low (n = 70; 24.9%; reference); moderate (n = 149; 53.0%); and high (62; 22.1%). Female sex (adjusted odds ratio (adjOR)_moderate = 3.10 [95% CI = 1.68-5.72]; adjOR_high = 5.76 [2.70-12.27]), higher depression/anxiety (adjOR_moderate = 1.47 [1.24-1.74]; adjOR_high = 1.72 [1.43-2.07]), and less social support (adjOR_moderate = 0.91 [0.83, 0.99]; adjOR_high = 0.86 [0.78-0.95]) were associated with moderate and high symptom burden. Geriatric conditions, including delirium (adjOR_high = 7.74 [1.56-38.26]), frailty (adjOR_high = 5.26 [1.77-15.68]), impairment of physical function (adjOR_high = 1.18 [1.00-1.40]), and vision impairment (adjOR_high = 4.63 [1.33-16.11]), were associated with high symptom burden.

Conclusions: In older persons hospitalized with COVID-19, female sex, psychosocial factors, and geriatric conditions were associated with higher symptom burden over six months. Future work should investigate the biopsychosocial mechanisms through which psychosocial factors and geriatric conditions contribute to post-COVID symptom burden.

Background: Frailty, defined as diminished physiological and functional reserve, is linked to negative health outcomes such as falls, fractures, and disability. Physical activity dose plays a significant role in preventing and reducing physical frailty, but the influence of different PA variables on deficit accumulation (ie, frailty index [FI]) is not fully understood. Thus, we examined the relationship between physical activity variables and FI among older adults.

Methods: We utilized Round 11 (2021) data from the National Health and Aging Trends Study, a longitudinal study of Medicare beneficiaries aged 65 and older in the United States. Our participants included 726 community-dwelling older adults who had at least 3 valid days of accelerometer data and all data needed to calculate FI. Demographic variables, health conditions, and physical function were assessed through standardized interviews and objective assessments. We completed regression and Poisson models to estimate FI value and prevalence ratios for frailty.

Results: Participants spent 339 daily minutes performing physical activity. The activity was accumulated over 88 bouts averaging 3.8 minutes. Those with frailty have lower levels of activity, higher levels of non-activity and sleep, higher activity fragmentation, fewer bouts, shorter bouts, and lower intensity over 10 consecutive minutes (ps < .001). After adjusting for all activity metrics, activity fragmentation (B = 1.32) and intensity of the most active 10-minute bout (B= -0.46) remained significantly associated with FI (P ≤ .04).

Conclusions: Low-intensity and fragmented physical activity is linked to frailty. Further research should explore the role of sustained activity and fragmentation in monitoring and guiding interventions for frailty.

Background: Alzheimer's disease and related dementias (ADRD) research worldwide indicate that it is more common in Indigenous than in non-Indigenous populations. We examined the relationship of depression and diabetes, alone and together, with incident ADRD in a large sample of American Indian and Alaska Native (AIAN) peoples.

Methods: We examined a sample of 65,801 AIAN peoples aged ≥ 45 years in fiscal year 2007 who were ADRD-free between FY2007-09. Cox proportional hazard models were employed to estimate associations between ADRD risk and baseline depression and diabetes, adjusting for potential confounding variables.

Results: We found 2.3% received an ADRD diagnosis during FY2010-13. Compared to persons with neither depression nor diabetes, the fully adjusted hazard ratio (HR) for those aged ≥ 45 years with depression and diabetes was 1.82 (95% CI 1.53-2.16) for ADRD and those with depression only had a hazard ratio of 1.70 (95% CI 1.44-2.00). A significant relationship was not found between diabetes only and ADRD risk. Compared with women without depression, the adjusted risk of ADRD was 50% higher (HR = 1.50, 95% CI 1.30-1.73) for women with depression, while 115% higher (HR = 2.15, 95% CI 1.76-2.61) for men with depression.

Conclusions: Depression is associated with a substantially higher risk of ADRD among adult AIAN peoples. This association varies by sex and age, with the strongest association observed among relatively young men. Helpful future efforts include ensuring clinical and behavioral services for AIAN peoples provide regular mental health screening and any needed treatment.

Background: Enhanced understanding of the use of palliative care among older adults with traumatic brain injury (TBI) could help guide development of policy and educational interventions. Our objective was to assess racial and ethnic disparities in the receipt of palliative care among older adults with TBI.

Methods: We conducted a cross-sectional study using data from the Premier Database from May 2022-May 2023. We included adults aged 65 and older with an admission diagnosis of TBI who died during hospitalization. We compared characteristics and palliative care receipt across racial/ethnic groups. Logistic regression models were used to estimate the unadjusted and adjusted odds of receiving palliative care as a function of race/ethnicity. The primary outcome was receipt of a palliative care consultation.

Results: Of 1,119 included patients,76.4% were Non-Hispanic White, 5.1% were Non-Hispanic Black, 5.5% were Hispanic, 4.4% were Asian, and 8.7% were classified as Other/Unknown. The majority (81.7%) received palliative care. In adjusted models, Non-Hispanic Black patients had the lowest odds of receiving a palliative care consultation compared to Non-Hispanic White patients (odds ratio (OR) 0.42; 95% confidence interval, 0.23-0.76).

Conclusions: In a cohort of older adults hospitalized with TBI who died in-hospital, Non-Hispanic Black patients were markedly less likely to receive palliative care compared to their White counterparts. This study underscores the need for future work to identify the extent to which historical mistrust, communication barriers, provider bias, and socioeconomic factors contribute to differences in palliative care access among older TBI patients.

Background: Whether the differing mechanistic effects between angiotensin-2 receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) on the renin-angiotensin system translate to differential effects on clinical cognitive outcomes is unclear.

Methods: We employed an active comparator, new-user cohort study to emulate a target trial evaluating the per-protocol effect of initiating and continuously adhering to an ARB versus ACEI on adjudicated amnestic mild cognitive impairment (MCI) and probable dementia (PD) in the Systolic Blood Pressure Intervention Trial (SPRINT). Inverse probability of treatment and censoring weighted cumulative incidence functions accounted for confounding, the competing risk of death, adherence, and loss to follow-up.

Results: Of 9,361 SPRINT participants (mean age 67.1 ± 9.5 years, 36.7% female, 58.7% non-Hispanic White), 710 and 1,289 were new users of an ARB or ACEI. Overall, 291 (41.0%) ARB initiators and 854 (66.3%) ACEI initiators were nonadherent during follow-up. The IP-weighted 4-year probabilities of full adherence and being alive among ARB was 56.0% (95% CI: 52.2%-59.9%) and 30.5% (95% CI: 28.0%-33.1%) for ACEI. The 4-year weighted risk ratios (RR) for amnestic MCI/PD and for amnestic MCI/PD/death with initiation and full adherence to ARB versus ACEI were 0.94 (95% CI: 0.66-1.29) and 0.79 (95% CI: 0.58-1.06). The weighted 4-year weighted RR for all-cause death with ARB versus ACEI initiation and adherence was 0.36 (95% CI: 0.14-0.76).

Conclusions: In this target trial emulation of older adults at high risk for cardiovascular disease, there was insufficient evidence to conclude a beneficial effect of initiating and continuously adhering to an ARB versus ACEI on adjudicated clinical cognitive outcomes.