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

The African turquoise killifish Nothobranchius furzeri represents an emerging short-lived model for aging research. Captive strains of this species are characterized by large differences in lifespan. To identify the gene expression correlates of this lifespan differences, we analyzed a public transcriptomic dataset consisting of four different tissues in addition to embryos. We focused on the GRZ and the MZM0410 captive strains, which show a near twofold difference in lifespan, but similar growth and maturation and validated the results in a newly-generated dataset from a third longer-lived strain. The two strains show distinct transcriptome expression patterns already as embryos and the genotype has a larger effect than age on gene expression, both in terms of number of differentially expressed genes and magnitude of regulation. Network analysis detected RNA processing and histone modifications as the most prominent categories upregulated in GRZ that also showed idiosyncratic expression patterns such as high expression of DND is somatic tissues. The short-lived GRZ strain shows transcriptional aging signatures already at sexual maturity (anticipated aging) in all four tissues suggesting that short lifespan is the results of events that occur early in life rather than the progressive accumulation of strain-dependent differences. The GRZ strain is the most commonly used N. furzeri strain in intervention studies and our results warrant replication of at least key intervention studies in longer-lived strains.

Background: The association between subclinical cardiovascular disease (CVD) and cognitive decline in hypertensive adults and the underlying brain pathologies remain unclear. It is also undetermined whether intensifying blood pressure (BP) treatment slows down cognitive decline associated with subclinical CVD.

Methods: We conducted a post hoc analysis of the Systolic Blood Pressure Intervention Trial. Subclinical CVD at baseline was identified by elevated levels of high-sensitivity cardiac troponin T (hs-cTnT≥14 ng/L) and N-terminal pro-B-type natriuretic peptide (NT-proBNP≥125 pg/mL). Global cognitive function and domain-specific measures (memory, processing speed, language, and executive function) were assessed at baseline and follow-up (years 2, 4, and 6) in 2733 participants. White matter lesions, cerebral blood flow, and brain tissue volume were assessed by MRI at baseline and years 4 in a subset of 639 participants.

Results: Both elevated hs-cTnT and NT-proBNP levels at baseline were associated with accelerated cognitive decline across all domains after adjusting for potential confounding factors. The group with elevated levels of both cardiac biomarkers showed the fastest decline, with a larger annual decline rate of 0.033 (95% CI: 0.024-0.041) in the z-score of global cognitive function compared to the group with normal levels. Elevated levels of both biomarkers were also associated with a faster progression in white matter lesions, but not with changes in total brain tissue volume or cerebral blood flow. Intensive BP treatment did not attenuate these associations compared to standard treatment.

Conclusions: Subclinical CVD may contribute to faster white matter lesion progression and accelerated cognitive decline in patients with hypertension, regardless of intensive BP treatment.

Excess adipose tissue may promote chronic systemic inflammation and oxidative stress, causing endothelial damage. Early evidence indicates that obesity may be associated with poorer cerebral perfusion. The purpose of this study was to examine the relationship between body composition and cerebral hemodynamics. A total of 248 middle-aged adults (50-58 years old; 55% women) underwent a ramp test on a cycle-ergometer until volitional exhaustion. Gas exchange was assessed on a breath-by-breath basis. Mean middle cerebral artery velocity (MCAv) was measured using transcranial Doppler, and pulsatility index (PI) was calculated. Body composition was assessed by dual X-ray absorptiometry. Statistical analyses were performed using a compositional data approach including a 3-compartment model for body composition (trunk fat mass, extremities fat mass, and fat-free mass). The unadjusted models for the whole sample showed that trunk fat mass relative to other compartments was negatively associated with MCAvrest, MCAvmax, and gain, and positively associated with PImax; extremities fat mass relative to other compartments was positively associated with MCAvrest and MCAvmax, and negatively associated with PImax; and fat-free mass relative to other compartments was positively associated with PImax. These associations were sex-dependent, remaining in the women's subgroup. However, after adjusting for confounders, these associations became nonsignificant, except for PImax in the whole sample and women's subgroup. These findings suggest a possible association between cerebral hemodynamics and body composition in middle-aged adults, highlighting sex-specific differences. Moreover, our results indicate that higher trunk fat mass relative to other compartments may negatively affect cerebral hemodynamics, reducing MCAv and increasing PImax.

Life expectancy has increased worldwide alongside a rise in disability prevalence during old age. The impact and interrelationship among the precursors of disability in midlife remain to be better understood. Furthermore, investigating whether lifestyle factors may potentially influence health outcomes and the prognosis of vascular disease could be especially relevant among the middle-aged population, which is a priority subpopulation when prevention is the goal. This is an observational, cross-sectional, and population-based study. Participants, between 50 and 55 years old, are randomly selected from the municipality of Toledo (Spain). There are 6 nonconsecutive days for the assessments, providing enough rest between evaluations. Participants perform the interview of the Toledo Study for Healthy Aging. Blood pressure monitoring and a resting electrocardiogram are also recorded. Then, resting peripheral and cerebral vascular measurements along with muscle size and architecture are assessed. Blood and urine samples and body composition data are collected after an overnight fasting. On a different visit, physical performance and muscle function tests are performed. Additionally, brain magnetic resonance imaging is conducted. And finally, an accelerometer is given to the participants for a week. Frailty is evaluated by the Frailty Trait Scale and Fried Frailty Phenotype. This project will shed light on the associations between frailty, early cognitive impairment, and vascular aging during midlife, and on the role that lifestyles play in their development. Lastly, this project will provide meaningful implications for public health strategies aimed at promoting healthy aging in later life.

Background: Patients with heart failure (HF) are at an increased risk of developing pneumonia, leading to a high mortality. A decrease in muscle strength due to aging or concomitant disease may contribute to the development of pneumonia in older adults. We sought to investigate the relationship between low muscle strength and pneumonia incidence in older patients hospitalized for worsening HF.

Methods: We carried out a subanalysis of the FRAGILE-HF, a prospective multicenter observational study, including 1 266 consecutive older (≥65 years) patients hospitalized with HF (mean age 80.2 ± 7.8 years; 57.4% male; left ventricular ejection fraction 46% ± 17%) and information of incident pneumonia observed after discharge. Patients were followed up for 2 years post-discharge.

Results: A total of 88 patients (7.0%) developed pneumonia after discharge, with an incidence of 42.7 per 1 000 person-years. A total of 893 patients with low muscle strength, defined as handgrip strength <28 kg for men and <18 kg for women according to international criteria, were more likely to develop pneumonia than those with normal muscle strength (p < .001; log-rank test). Low muscle strength was a significant predictor of incident pneumonia (adjusted hazard ratio with 95% confidence interval: 2.65 [1.31-5.35], p = .007). Furthermore, the mortality rates were 43.2% in patients who developed pneumonia and 19.3% in those who did not, indicating a heightened risk of death following the onset of pneumonia (adjusted hazard ratio: 4.25 [2.91-6.19], p < .001).

Conclusions: In older patients hospitalized for HF, low muscle strength was associated with incident pneumonia after discharge.

Background: Although the pathogenesis of delirium is poorly understood, increasing evidence supports a role for inflammation. Previously, individual inflammatory biomarkers have been associated with delirium. Aggregating biomarkers into an index may provide more information than individual biomarkers in predicting certain health outcomes (eg, mortality); however, inflammatory indices have not yet been examined in delirium.

Methods: Four inflammatory markers, C-reactive protein, interleukin-6, soluble tumor necrosis factor alpha receptor-1, and chitinase-3 like protein-1, were measured preoperatively and on postoperative day 2 in 548 adults aged 70+ undergoing major noncardiac surgery (mean age 76.7 [standard deviation 5.2], 58% female, 24% delirium). From these markers, 4 inflammatory indices were considered: (i) quartile summary score, (ii) weighted summary score, (iii) principal component score, and (iv) a well-established inflammatory (least absolute shrinkage and selection operator-derived) index associated with mortality. Delirium was assessed using the Confusion Assessment Method, supplemented by chart review. Generalized linear models with a log-link term were used to determine the association between each inflammatory index and delirium incidence.

Results: Among the inflammatory indices, the weighted summary score demonstrated the strongest association with delirium: participants in the weighted summary score quartile (Q)4 had a higher risk of delirium versus participants in Q1, after clinical variable adjustment (relative risk, 95% confidence interval for preoperatively: 3.07, 1.80-5.22; and postoperative day 2: 2.65, 1.63-4.30). The weighted summary score was more strongly associated with delirium than the strongest associated individual inflammatory marker (preoperatively chitinase-3 like protein-1 [relative risk 2.45, 95% confidence interval 1.53-3.92]; postoperative day 2 interleukin-6 [relative risk 2.39, 95% confidence interval 1.50-3.82]).

Conclusions: A multi-protein inflammatory index using a weighted summary score provides a slight advantage over individual inflammatory markers in their association with delirium.

Background: The involvement of older adults in research on digital health is uneven with respect to, for example, age, gender, health status, and digital skills. However, little is known regarding the effect of the uneven involvement of older adults in digital health research on researched outcomes. This study helps to fill this knowledge gap, identifies the effects of uneven involvement of older adults in digital health research on researched outcomes, and also develops a correction for this.

Methods: Data are retrieved from a digital health intervention for postoperative monitoring of people who underwent day surgery in Sweden. Based on field information on the recruitment process and researched outcomes for the intervention, this study (i) tested intervention effects by using 2 standard unweighted procedures in a sample of 281 individuals aged 50 years or older, and then (ii) used the information on participants, nonparticipants, and their respective probabilities to be involved in the intervention study to perform a weighting of the intervention effects for each step of selection and for the study group membership.

Results: The intervention effects were found to be overestimated due to overrepresentation of groups that gained from receiving the intervention. No intervention effects were found after adjustment for participation bias.

Conclusions: Selective participation of older adults in digital health research biases research outcomes and can lead to overestimation of intervention effects. Weighting allows researchers to correct and describe the effect of selective participation on researched outcomes.

Background: Mild cognitive impairment (MCI) and parkinsonism affect many older adults. The objective of this study was to determine the sequence of their occurrence and associated risk of death.

Methods: A total of 1255 community-dwelling unimpaired participants from 2 epidemiological cohorts were examined annually. MCI was based on neuropsychological testing and parkinsonism was based on the motor portion of the modified Unified Parkinson's Disease Rating Scale. A multistate Cox proportional hazards model simultaneously examined incidences of MCI, parkinsonism, and death.

Results: The average age at baseline was 76.5 years (standard deviation [SD] = 7.2) and 73% were female. Incident MCI occurred almost as commonly as incident parkinsonism, yet compared with no impairment, the risk of death was higher for MCI (hazard ratio [HR] = 1.82, 95% confidence interval [CI] = 1.34, 2.47), but it was not different for parkinsonism (HR = 1.29; 95% CI =0.95, 1.75). The risk of death for participants with incident MCI who progressed to parkinsonism (40%) was not significantly different from those with MCI alone (HR = 1.25, 95% CI = 0.93, 1.69). However, the risk of death for participants with incident parkinsonism who progressed to MCI (51%) was significantly higher than those who did not progress (HR = 1.67, 95% CI = 1.27, 2.18), indicating that the risk of death is highest with the incidence of MCI.

Conclusions: The varied patterns of sequential occurrence of cognitive and motor impairment and associated risk of death suggest much greater heterogeneity than previously recognized. Further work is needed to determine the biology underlying the temporal evolution of these phenotypes, and if identification of the various subtypes improves risk stratification.

Background: Current multimorbidity measures often oversimplify complex disease interactions by assuming a merely additive impact of diseases on health outcomes. This oversimplification neglects clinical observations that certain disease combinations can exhibit synergistic effects. Thus, we aimed to incorporate simultaneous higher-order disease interactions into the validated ICD-coded multimorbidity-weighted index, to assess for model improvement.

Methods: Health and Retirement Study participants with linked Medicare data contributed ICD-9-CM claims, 1991-2012. Top 20 most prevalent and impactful conditions (based on associations with decline in physical functioning) were assessed through higher-order interactions (2-way, 3-way). We applied the least absolute shrinkage and selection operator and bootstrapping to identify and retain statistically significant disease interactions. We compared model fit in multimorbidity-weighted index with and without disease interactions in linear models.

Results: We analyzed 73 830 observations from 18 212 participants (training set N = 14 570, testing set N = 3 642). Multimorbidity-weighted index without interactions produced an overall R2 = 0.26. Introducing 2-way interactions for the top 10 most prevalent and impactful conditions resulted in a R2 = 0.27, while expanding to top 20 most prevalent and impactful conditions yielded a R2 = 0.26. When adding 3-way interactions, the same top 10 conditions produced a R2 = 0.26, while expanding to top 20 conditions resulted in a R2 = 0.24.

Conclusions: We present novel insights into simultaneous higher-order disease interactions for potential integration into multimorbidity measurement. Incorporating 2-way disease interactions for the top 10 most prevalent and impactful conditions showed a minimal improvement in model fit. A more precise multimorbidity index may incorporate both the main effects of diseases and their significant interactions.