Life Span Study Research Articles

Persistent homology-based functional connectivity and its association with cognitive ability: Life-span study.

Brain-segregation attributes in resting-state functional networks have been widely investigated to understand cognition and cognitive aging using various approaches [e.g., average connectivity within/between networks and brain system segregation (BSS)]. While these approaches have assumed that resting-state functional networks operate in a modular structure, a complementary perspective assumes that a core-periphery or rich club structure accounts for brain functions where the hubs are tightly interconnected to each other to allow for integrated processing. In this article, we apply a novel method, persistent homology (PH), to develop an alternative to standard functional connectivity by quantifying the pattern of information during the integrated processing. We also investigate whether PH-based functional connectivity explains cognitive performance and compare the amount of variability in explaining cognitive performance for three sets of independent variables: (1) PH-based functional connectivity, (2) graph theory-based measures, and (3) BSS. Resting-state functional connectivity data were extracted from 279 healthy participants, and cognitive ability scores were generated in four domains (fluid reasoning, episodic memory, vocabulary, and processing speed). The results first highlight the pattern of brain-information flow over whole brain regions (i.e., integrated processing) accounts for more variance of cognitive abilities than other methods. The results also show that fluid reasoning and vocabulary performance significantly decrease as the strength of the additional information flow on functional connectivity with the shortest path increases. While PH has been applied to functional connectivity analysis in recent studies, our results demonstrate potential utility of PH-based functional connectivity in understanding cognitive function.

Association of Race and Poverty Status With DNA Methylation–Based Age

The Dunedin Pace of Aging Calculated From the Epigenome (DunedinPACE) measure is a newly constructed DNA methylation (DNAm) biomarker associated with morbidity, mortality, and adverse childhood experiences in several cohorts with European ancestry. However, there are few studies of the DunedinPACE measure among socioeconomically and racially diverse cohorts with longitudinal assessments. To investigate the association of race and poverty status with DunedinPACE scores in a socioeconomically diverse middle-aged cohort of African American and White participants. This longitudinal cohort study used data from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study. HANDLS is a population-based study of socioeconomically diverse African American and White adults aged 30 to 64 years at baseline in Baltimore, Maryland, with follow-up approximately every 5 years. The current study was restricted to 470 participants with blood samples at 2 time points: August 14, 2004, to June 22, 2009 (visit 1), and June 23, 2009, to September 12, 2017 (visit 2). Genome-wide DNAm was assessed at visit 1 (chronological age, 30-64 years) and visit 2. Data were analyzed from March 18, 2022, to February 9, 2023. DunedinPACE scores were estimated for each participant at 2 visits. DunedinPACE scores are values scaled to a mean of 1, interpretable with reference to a rate of 1 year of biological aging per 1 year of chronological aging. Linear mixed-model regression analysis was used to examine the trajectories of DunedinPACE scores by chronological age, race, sex, and poverty status. Among 470 participants, the mean (SD) chronological age at visit 1 was 48.7 (8.7) years. Participants were balanced by sex (238 [50.6%] were men and 232 [49.4%] were women), race (237 [50.4%] African American and 233 [49.6%] White), and poverty status (236 [50.2%] living below poverty level and 234 [49.8%] living above poverty level). The mean (SD) time between visits was 5.1 (1.5) years. Overall, the mean (SD) DunedinPACE score was 1.07 (0.14), representing a 7% faster pace of biological aging than chronological aging. Linear mixed-effects regression analysis revealed an association between the 2-way interaction between race and poverty status (White race and household income below poverty level: β = 0.0665; 95% CI, 0.0298-0.1031; P < .001) and significantly higher DunedinPACE scores and an association between quadratic age (age squared: β = -0.0113; 95% CI, -0.0212 to -0.0013; P = .03) and significantly higher DunedinPACE scores. In this cohort study, household income below poverty level and African American race were associated with higher DunedinPACE scores. These findings suggest that the DunedinPACE biomarker varies with race and poverty status as adverse social determinants of health. Consequently, measures of accelerated aging should be based on representative samples.

Allostatic Load and Cognitive Function Among Urban Adults in the Healthy Aging in Neighborhoods of Diversity across the Life Span Study.

Cross-sectional studies have linked cognition to allostatic load (AL) which reflects multisystem dysregulation from life course exposure to stressors. To examine baseline and changes in AL and their relationships with 11 cognitive function test scores, while exploring health disparities according to sex and race. Longitudinal [Visit 1 (2004-2009) and Visit 2 (2009-2013)] data were analyzed from 2,223 Healthy Aging in Neighborhoods of Diversity across the Life Span participants. We calculated AL total score using cardiovascular, metabolic, and inflammatory risk indicators, and applied group-based trajectory modeling to define AL change. Overall and stratum-specific relationships were evaluated using mixed-effects linear regression models that controlled for socio-demographic, lifestyle, and health characteristics. Baseline AL was significantly associated with higher log-transformed Part A Trail Making Test score [Loge (TRAILS A)] (β= 0.020, p = 0.004) and increasing AL was associated with higher Benton Visual Retention Test score [BVRT] (β= 0.35, p = 0.002) at baseline, in models that controlled for age, sex, race, poverty status, education, literacy, smoking, drug use, the 2010 healthy eating index and body mass index. Baseline AL and AL change were not related to change in cognitive function between visits. There were no statistically significant interaction effects by sex or race in fully-adjusted models. At baseline, AL was associated with worse attention or executive functioning. Increasing AL was associated with worse non-verbal memory or visuo-constructional abilities at baseline. AL was not related to change in cognitive function over time, and relationships did not vary by sex or race.

Association of Antenatal COVID-19–Related Stress With Postpartum Maternal Mental Health and Negative Affectivity in Infants

Antenatal stress is a significant risk factor for poor postpartum mental health. The association of pandemic-related stress with postpartum outcomes among mothers and infants is, however, less well understood. To examine the association of antenatal COVID-19-related stress with postpartum maternal mental health and infant outcomes. This cohort study was conducted among 318 participants in the COVID-19 Risks Across the Lifespan study, which took place in Australia, the UK, and the US. Eligible participants reported being pregnant at the first assessment wave between May 5 and September 30, 2020, and completed a follow-up assessment between October 28, 2021, and April 24, 2022. COVID-19-related stress was assessed with the Pandemic Anxiety Scale (score range, 0-4, with higher scores indicating greater COVID-19-related stress). The 8-item Patient Health Questionnaire (score range, 0-3, with higher scores indicating more frequent symptoms of depression) was used to measure maternal depression at each time point, and the 7-item General Anxiety Disorder scale (score range, 0-3, with higher scores indicating more frequent symptoms of anxiety) was used to measure generalized anxiety at each time point. At follow-up, postpartum distress was assessed with the 10-item Postpartum Distress Measure (score range, 0-3, with higher scores indicating greater postpartum distress), and infant outcomes (negative and positive affectivity and orienting behavior) were captured with the Infant Behavior Questionnaire (score range, 1-7, with higher scores indicating that the infant exhibited that affect/behavior more frequently). The study included 318 women (mean [SD] age, 32.0 [4.6] years) from Australia (88 [28%]), the US (94 [30%]), and the UK (136 [43%]). Antenatal COVID-19-related stress was significantly associated with maternal postpartum distress (β = 0.40 [95% CI, 0.28-0.53]), depression (β = 0.32 [95% CI, 0.23-0.41]), and generalized anxiety (β = 0.35 [95% CI, 0.26-0.44]), as well as infant negative affectivity (β = 0.45 [95% CI, 0.14-0.76]). The findings remained consistent across a range of sensitivity analyses. The findings of this cohort study suggest that targeting pandemic-related stressors in the antenatal period may improve maternal and infant outcomes. Pregnant individuals should be classified as a vulnerable group during pandemics and should be considered a public health priority, not only in terms of physical health but also mental health.

Shared genetic architecture between attention-deficit/hyperactivity disorder and lifespan

There is evidence linking ADHD to a reduced life expectancy. The mortality rate in individuals with ADHD is twice that of the general population and it is associated with several factors, such as unhealthy lifestyle behaviors, social adversity, and mental health problems that may in turn increase mortality rates. Since ADHD and lifespan are heritable, we used data from genome-wide association studies (GWAS) of ADHD and parental lifespan, as proxy of individual lifespan, to estimate their genetic correlation, identify genetic loci jointly associated with both phenotypes and assess causality. We confirmed a negative genetic correlation between ADHD and parental lifespan (rg = −0.36, P = 1.41e−16). Nineteen independent loci were jointly associated with both ADHD and parental lifespan, with most of the alleles that increased the risk for ADHD being associated with shorter lifespan. Fifteen loci were novel for ADHD and two were already present in the original GWAS on parental lifespan. Mendelian randomization analyses pointed towards a negative causal effect of ADHD liability on lifespan (P = 1.54e−06; Beta = −0.07), although these results were not confirmed by all sensitivity analyses performed, and further evidence is required. The present study provides the first evidence of a common genetic background between ADHD and lifespan, which may play a role in the reported effect of ADHD on premature mortality risk. These results are consistent with previous epidemiological data describing reduced lifespan in mental disorders and support that ADHD is an important health condition that could negatively affect future life outcomes.

Too easy, too hard, or just right: Lifespan age differences and gender effects on task difficulty choices

In everyday life, individuals often need to make choices about the difficulty level of tasks they wish to perform. Here, we investigate age- and gender-related differences in the monitoring of discrepancies between the difficulty of a given task and one’s own performance level, and in the likelihood to select task difficulties that match one’s performance level. Male and female children, teenagers, younger adults, and older adults (total N = 160) were asked to play a modified version of the BINGO game. Task difficulty was operationalized as the number of cards played simultaneously. We expected that (a) discrepancies between individuals’ self-selected difficulty levels and their objectively assessed maximum manageable task difficulty (MMTD) would be lowest in early adulthood; (b) children and teenagers, on average, would select relatively difficult task difficulties; and (c) males would overestimate their performance levels, on average, to a greater extent than females. As predicted, younger adults selected task difficulties closest to their MMTD. All other age groups, including older adults, chose task difficulties above their MMTD. The expected gender differences were restricted to children, with boys showing more pronounced performance overestimations than girls. Children and teenagers fluctuated more in their difficulty choices than adults, and many of them, especially boys, occasionally chose difficulty levels far beyond their performance capabilities. We conclude that task-difficulty choices are an interesting topic for lifespan studies. Future research should systematically vary the physical risk involved in a task, and also include the presence of peers.

Discussion of uncertainties and the impact of different neutron RBEs on all solid cancer radiation incidence risks obtained from the Japanese A-bomb survivor data.

The most recent publicly available data on all solid cancer incidence from the Life Span Study (LSS) of Japanese A-bomb survivors provides colon dose contributions weighted with a relative biological effectiveness (RBE) of 10 for neutrons, relative to gammas. However, there is evidence from several investigations that the neutron RBE for A-bomb survivors may be higher than 10. The change in the shape of the corresponding dose-response curves was evaluated by Hafner and co-workers in a previous study by applying sex-specific linear-quadratic dose models to previous LSS data for all solid cancer incidence that include separate neutron and gamma absorbed doses for several organs, in contrast to the most recent data. The resulting curvature change became significantly negative for males at an RBE of 140 for colon, 100 for liver, and 80 for organ averaged dose. For females, the corresponding RBE values were 110, 80, and 60 for colon, liver, and organ averaged doses. The present study compares three different methods to calculate the 95% confidence intervals in an analysis of the curvature with increasing RBE. Further, the impact of a higher neutron RBE on the work of the International Commission on Radiological Protection, and the importance of including uncertainties and performing sensitivity analysis of different parameters in radiation risk assessment are discussed.

Natural ageing primarily affects the initial response to a sustained walking perturbation but not the ability to adapt over time.

The ability to flexibly respond and adapt the walking pattern over time to unexpected gait perturbations is pivotal for safe and efficient locomotion. However, these abilities might be affected by age due to age-related changes in sensorimotor functioning. In this cross-sectional lifespan study, we used a split-belt paradigm to determine how age affects the initial response (i.e., flexibility)-and the ability to adapt after prolonged exposure-to a sustained gait perturbation. Healthy adults (N = 75) of different ages (12-13 per decade) were included and walked on a split-belt treadmill, in which a sustained gait perturbation was imposed by increasing one of the belt speeds. Linear regression models, with the evoked spatiotemporal gait asymmetry during the early perturbation and late adaptation, were performed to determine the effects of age on the flexibility and adaptability to split-belt walking. Results showed that the flexibility to respond to an unexpected perturbation decreased across the lifespan, as evidenced by a greater step length asymmetry (SLA) during the early perturbation phase. Despite this reduced flexibility in step lengths, late adaptation levels in SLA were comparable across different ages. With increasing age, however, subjects needed more steps to reach a stable level in SLA. Finally, when the belts were set to symmetrical speeds again, the magnitude of SLA (i.e., the aftereffects) increased with age. Collectively, these findings suggest that natural ageing comes with a decrease in gait flexibility, while the ability to adapt to split-belt walking was not affected by age-only how adaptation was achieved.

Effect of radiation exposure on survival after first solid cancer diagnosis in A-bomb survivors

BackgroundComparison of the estimated effect of atomic bomb radiation exposure on solid cancer incidence and solid cancer mortality in the RERF Life Span Study (LSS) reveals a difference in the magnitude and shape of the excess relative risk dose response. A possible contributing factor to this difference is pre-diagnosis radiation effect on post-diagnosis survival. Pre-diagnosis radiation exposure theoretically could influence post-diagnosis survival by affecting the genetic makeup and possibly aggressiveness of cancer, or by compromising tolerance for aggressive treatment for cancer. MethodsWe analyze the radiation effect on post-diagnosis survival in 20,463 LSS subjects diagnosed with first-primary solid cancer between 1958 and 2009 with particular attention to whether death was caused by the first-primary cancer, other cancer, or non-cancer diseases. ResultsFrom multivariable Cox regression analysis of cause-specific survival, the excess hazard at 1 Gy (EH1Gy) for death from the first primary cancer was not significantly different from zero – p = 0.23, EH1Gy = 0.038 (95 % CI: −0.023, 0.104). Death from other cancer and death from non-cancer diseases both were significantly associated with radiation dose: other cancer EH1Gy = 0.38 (95 % CI: 0.24, 0.53); non-cancer EH1Gy = 0.24 (95 % CI: 0.13, 0.36), both p < 0.001. ConclusionThere is no detectable large effect of pre-diagnosis radiation exposure on post-diagnosis death from the first primary cancer in A-bomb survivors. ImpactA direct effect of pre-diagnosis radiation exposure on cancer prognosis is ruled out as an explanation for the difference in incidence and mortality dose response in A-bomb survivors.

Tryptophan Metabolism and Neurodegeneration: Longitudinal Associations of Kynurenine Pathway Metabolites with Cognitive Performance and Plasma Alzheimer's Disease and Related Dementias Biomarkers in the Duke Physical Performance Across the LifeSpan Study.

The kynurenine pathway (KP) comprises a family of tryptophan-derived metabolites that some studies have reported are associated with poorer cognitive performance and an increased risk of Alzheimer's disease and related dementias (ADRD). The objective of this study was to determine the associations of plasma KP metabolites (kynurenine [KYN], kynurenic acid [KA], and tryptophan [TRP]) with a panel of plasma ADRD biomarkers (Aβ42/ β40 ratio, pTau-181, glial fibrillary acidic protein [GFAP], and neurofilament light [NfL]) and cognitive performance in a subset of older adults drawn from the Duke Physical Performance Across the LifeSpan (PALS) study. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance. We used multivariate multiple regression to evaluate associations of the KYN/TRP and KA/KYN ratios with MoCA score and plasma ADRD biomarkers at baseline and over two years (n = 301; Age = 74.8±8.7). Over two years, an increasing KYN/TRP ratio was associated with increasing plasma concentrations of plasma p-Tau181 (β= 6.151; 95% CI [0.29, 12.01]; p = 0.040), GFAP (β= 11.12; 95% CI [1.73, 20.51]; p = 0.020), and NfL (β= 11.13; 95% CI [2.745, 19.52]; p = 0.009), but not MoCA score or the Aβ42/Aβ40 ratio. There were no significant associations of KA/KYN with MoCA score or plasma ADRD biomarkers. Our findings provide evidence that greater concentrations of KP metabolites are associated longitudinally over two years with greater biomarker evidence of neurofibrillary tau pathology (pTau-181), neuroinflammation (GFAP), and neurodegeneration (NfL), suggesting that dysregulated KP metabolism may play a role in ADRD pathogenesis.

Exploring Sociodemographic Correlates of Suicide Stigma in Australia: Baseline Cross-Sectional Survey Findings from the Life-Span Suicide Prevention Trial Studies.

The risk of suicidal behaviour in Australia varies by age, sex, sexual preference and Indigenous status. Suicide stigma is known to affect suicide rates and help-seeking for suicidal crises. The aim of this study was to investigate the sociodemographic correlates of suicide stigma to assist in prevention efforts. We surveyed community members and individuals who had attended specific emergency departments for suicidal crisis. The respondents were part of a large-scale suicide prevention trial in New South Wales, Australia. The data collected included demographic characteristics, measures of help-seeking and suicide stigma. The linear regression analyses conducted sought to identify the factors associated with suicide stigma. The 5426 participants were predominantly female (71.4%) with a mean (SD) age of 41.7 (14.8) years, and 3.9% were Indigenous. Around one-third of participants reported a previous suicide attempt (n = 1690, 31.5%) with two-thirds (n = 3545, 65.3%) seeking help for suicidal crisis in the past year. Higher stigma scores were associated with Indigenous status (β 0.123, 95%CI 0.074-0.172), male sex (β 0.527, 95%CI 0.375-0.626) and regional residence (β 0.079, 95%CI 0.015-0.143). Lower stigma scores were associated with younger age (β -0.002, 95%CI -0.004--0.001), mental illness (β -0.095, 95%CI -0.139 to -0.050), male bisexuality (β -0.202, 95%CI -0.351 to -0.052) and males who glorified suicide (β -0.075, 95%CI -0.119 to -0.031). These results suggested that suicide stigma differed across the community, varying significantly by sex, sexual orientation and Indigenous status. Targeted educational programs to address suicide stigma could assist in suicide prevention efforts.

Mitochondrial DNA and inflammatory proteins are higher in extracellular vesicles from frail individuals

BackgroundFrailty, a clinical syndrome commencing at midlife, is a risk for morbidity and mortality. Little is known about the factors that contribute to the chronic inflammatory state associated with frailty. Extracellular vesicles (EVs) are small, membrane-bound vesicles that are released into the circulation and are mediators of intercellular communication. We examined whether mitochondrial DNA (mtDNA) and inflammatory proteins in EVs may act as damage-associated molecular pattern (DAMP) molecules in frailty.ResultsTo address whether EVs and their associated mtDNA and inflammatory protein cargo are altered with frailty, EVs were isolated from non-frail (n = 90) and frail (n = 87) middle-aged (45–55 years) participants from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. EV concentration was highest in frail White participants. EV mtDNA levels were significantly higher in frail individuals compared to non-frail individuals. The presence of six inflammatory proteins in EVs (FGF-21, HGF, IL-12B, PD-L1, PRDX3, and STAMBP) were significantly associated with frailty. EV inflammatory proteins were significantly altered by frailty status, race, sex, and poverty status. Notably, frail White participants had higher levels of EV-associated CD5, CD8A, CD244, CXCL1, CXCL6, CXCL11, LAP-TGF-beta-1 and MCP-4 compared to frail and non-frail African American participants. Frail White participants living below poverty had higher levels of EV-associated uPA. EV-associated CCL28 levels were highest in non-frail women and CXCL1 were highest in non-frail men. Men living below poverty had higher levels of CD5, CD8A, CXCL1, LAP-TGF-beta-1, and uPA. CXCL6 levels were significantly higher in individuals living above poverty. There was a significant correlation between EV mtDNA levels and the presence of inflammatory proteins.ConclusionsThese data suggest that mtDNA within EVs may act as a DAMP molecule in frailty. Its association with chemokines and other inflammatory EV cargo proteins, may contribute to the frailty phenotype. In addition, the social determinant of health, poverty, influences the inflammatory cargo of EVs in midlife.

Comparison and multi-model inference of excess risks models for radiation-related solid cancer

In assessments of detrimental health risks from exposures to ionising radiation, many forms of risk to dose–response models are available in the literature. The usual practice is to base risk assessment on one specific model and ignore model uncertainty. The analysis illustrated here considers model uncertainty for the outcome all solid cancer incidence, when modelled as a function of colon organ dose, using the most recent publicly available data from the Life Span Study on atomic bomb survivors of Japan. Seven recent publications reporting all solid cancer risk models currently deemed plausible by the scientific community have been included in a model averaging procedure so that the main conclusions do not depend on just one type of model. The models have been estimated with different baselines and presented for males and females at various attained ages and ages at exposure, to obtain specially computed model-averaged Excess Relative Risks (ERR) and Excess Absolute Risks (EAR). Monte Carlo simulated estimation of uncertainty on excess risks was accounted for by applying realisations including correlations in the risk model parameters. Three models were found to weight the model-averaged risks most strongly depending on the baseline and information criteria used for the weighting. Fitting all excess risk models with the same baseline, one model dominates for both information criteria considered in this study. Based on the analysis presented here, it is generally recommended to take model uncertainty into account in future risk analyses.

Social and cognitive vulnerability to COVID-19-related stress in pregnancy: A case-matched-control study of antenatal mental health

Emerging evidence shows that compared to pre-pandemic norms pregnant women report significant increases in clinical levels of depressive and anxiety symptoms during COVID-19. This pre-registered study examined cognitive and social vulnerability factors for poor mental health in pregnancy during COVID-19. Understanding vulnerability profiles is key to identifying women at risk for deteriorating peripartum mental health. N = 742 pregnant women and N = 742 age and country-matched controls from the COVID-19 Risks Across the Lifespan Study were included. Using a case-match control design allowed us to explore whether the cognitive vulnerability profiles would differ between pregnant and non-pregnant women. The findings showed that COVID-19-related stress was associated with heightened levels of depression and anxiety during pregnancy. Its impact was greatest in women with cognitive (i.e., higher intolerance of uncertainty and tendency to worry) and social (i.e., higher level of self-reported loneliness) vulnerabilities. Importantly, our data show that the mental health impacts of the pandemic were greater in pregnant women compared to women who were not pregnant, especially those with cognitive and social vulnerabilities. The results highlight the urgent need to prioritize mental health care for pregnant women to mitigate the impact of COVID-19-related stress on women's postpartum mental health and their infants' well-being.

Testing the evidence that lifespan-extending compound interventions are conserved across laboratory animal model species.

A growing number of pharmaceutical and small molecule interventions are reported to extend the lifespan of laboratory animals including Caenorhabditis, Drosophila, and mouse. However, the degree to which these pro-longevity interventions are conserved across species is unclear. Here, we took two approaches to ask the question: to what extent do longevity intervention studies in Caenorhabditis and Drosophila recapitulate effects on mouse lifespan? The first approach analyzes all published reports on longevity in the literature collated by the DrugAge database, and the second approach focused on results designed for reproducibility as reported from the NIA-supported Interventions Testing Program (ITP) and the Caenorhabditis Interventions Testing Program (CITP). Using published data sources, we identify only modest sensitivity and specificity of Drosophila interventional studies for identifying pro-longevity compounds in mouse lifespan studies. Surprisingly, reported studies in C. elegans show little predictive value for identifying drugs that extend lifespan in mice. The results therefore suggest caution should be used when making assumptions about the translatability of lifespan-extending compounds across species, including human intervention.

Developmental and aging resting functional magnetic resonance imaging brain state adaptations in adolescents and adults: A large N (>47K) study.

The brain's functional architecture and organization undergo continual development and modification throughout adolescence. While it is well known that multiple factors govern brain maturation, the constantly evolving patterns of time-resolved functional connectivity are still unclear and understudied. We systematically evaluated over 47,000 youth and adult brains to bridge this gap, highlighting replicable time-resolved developmental and aging functional brain patterns. The largest difference between the two life stages was captured in a brain state that indicated coherent strengthening and modularization of functional coupling within the auditory, visual, and motor subdomains, supplemented by anticorrelation with other subdomains in adults. This distinctive pattern, which we replicated in independent data, was consistently less modular or absent in children and presented a negative association with age in adults, thus indicating an overall inverted U-shaped trajectory. This indicates greater synchrony, strengthening, modularization, and integration of the brain's functional connections beyond adolescence, and gradual decline of this pattern during the healthy aging process. We also found evidence that the developmental changes may also bring along a departure from the canonical static functional connectivity pattern in favor of more efficient and modularized utilization of the vast brain interconnections. State-based statistical summary measures presented robust and significant group differences that also showed significant age-related associations. The findings reported in this article support the idea of gradual developmental and aging brain state adaptation processes in different phases of life and warrant future research via lifespan studies to further authenticate the projected time-resolved brain state trajectories.

Longitudinal association of allostatic load with depressive symptoms among urban adults: Healthy Aging in Neighborhoods of Diversity across the Life Span study

BackgroundEvidence suggests that lifetime exposure to stressful life events and chronic stressors may be linked to geriatric depression. Allostatic load (AL) is considered a mediator of the stress-health relationship and has been linked to psychosocial factors reflecting health disparities. The purpose of this study was to examine the longitudinal associations of AL with depressive symptoms scores among urban adults, before and after stratifying by sex and race. MethodsSecondary analyses were performed using Visit 1 (2004–2009), Visit 2 (2009–2013) and Visit 3 (2013–2017) data collected on 2298 Healthy Aging in Neighborhoods of Diversity across the Life Span study participants (baseline age: 30–64 y). AL at Visit 1 (ALv1) and z-transformed probability of higher AL trajectory (ALtraj) between Visits 1 and 3 were calculated using cardiovascular, metabolic and inflammatory risk indicators. The 20-item Center for Epidemiologic Studies Depression (CES-D) scale was used to calculate total and domain-specific depressive symptoms scores. Mixed-effects linear models controlled for socio-demographic, lifestyle and health characteristics. ResultsIn fully adjusted models, a positive cross-sectional relationship was observed between ALv1 and “somatic complaints” depressive symptoms (β = 0.21, P = 0.006) score at Visit 1, whereas ALtraj was associated with increasing depressive symptoms score (β = 0.086, P = 0.003) between Visits 1 and 3. An inverse relationship was observed between ALtraj and “positive affect” depressive symptoms score at Visit 1 among women (β = −0.31, P < 0.0001) and White adults (β = −0.32, P = 0.004). Among women, ALtraj was also positively related to change in “somatic complaints” depressive symptoms score between Visits 1 and 3 (β = 0.043, P = 0.020). ConclusionsAmong urban adults, AL may be associated with “somatic complaints” depressive symptoms at baseline. Higher AL trajectories may predict increasing depressive symptoms (overall) and increasing “somatic complaints” depressive symptoms (among women). A higher AL trajectory may be associated with lower “positive affect” depressive symptoms at baseline among women and White adults only.

Mathematical modeling the gene mechanism of colorectal cancer and the effect of radiation exposure.

Cancer is the result of continuous accumulation of gene mutations in normal cells. The number of mutations is different in different types of cancer and even in different patients with the same type of cancer. Therefore, studying all possible numbers of gene mutations in malignant cells is of great value for the understanding of tumorigenesis and the treatment of cancer. To this end, we applied a stochastic mathematical model considering the clonal expansion of any premalignant cells with different mutations to analyze the number of gene mutations in colorectal cancer. The age-specific colorectal cancer incidence rates from the Surveillance, Epidemiology and End Results (SEER) registry in the United States and the Life Span Study (LSS) in Nagasaki and Hiroshima, Japan are chosen to test the reasonableness of the model. Our fitting results indicate that the transformation from normal cells to malignant cells may undergo two to five driver mutations for colorectal cancer patients without radiation-exposed environment, two to four driver mutations for colorectal cancer patients with low level radiation-exposure, and two to three driver mutations for colorectal cancer patients with high level radiation-exposure. Furthermore, the net growth rate of the mutated cells with radiation-exposure was is higher than that of the mutated cells without radiation-exposure for the models with two to five driver mutations. These results suggest that radiation environment may affect the clonal expansion of cells and significantly affect the development of tumors.

SIN NOMBRE NO HAY FAMA: UN ANALISIS BIBLIOMETRICO SOBRE ALTAS CAPACIDADES EN ADULTOS

The aim of the present study is to conduct a systematic review and analysis of the literature on gifted adults to explore the state of research in this area. A bibliometric science mapping tool, based on co-word analysis and h-index, is applied using the Science Mapping Analysis Software Tool (SciMAT). Initially, 661 articles published between 1948 and 2022 were retrieved from the Web of Science (WoS). Refined by English language and specific descriptors, 376 results were considered, and 28 themes and 32 clusters were identified as significant in the giftedness literature. Supported by life-span studies and earlier work on ability, data analysis revealed that adult giftedness is an emerging topic of research with a tentative development only a decade ago. The emergence of studies on giftedness in adults appears to be driven not only by cognitive testing (i.e., intelligence studies) or achievement research, but also, and more recently, by life satisfaction studies and the use of qualitative methodologies.

VIGILANCE, STRESS COPING, AND DISPARITIES IN METABOLIC HEALTH OVER THE LIFE COURSE

Abstract Recent investigations of the mechanisms through which stress may impact cardiometabolic health point to the potential importance of cognitive tendencies (e.g., vigilance, coping strategies) in this relationship. This study examined the associations between vigilance and stress coping with metabolic risk, and whether these associations varied by race and life course socioeconomic status (SES). Data come from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, a cohort of urban adults (n=3720, baseline age 30-64 years; balanced by race, sex, age and household income). Vigilance was measured by the MacArthur Reactive Responding subscale; stress coping was measured by the Brief Cope scale. Metabolic risk was operationalized by metabolic syndrome z-scores (MetS-Z). Linear mixed models were used to examine longitudinal associations between cognitive tendencies and MetS-Z; interaction terms were used to examine effect modification by race and life course SES. Black participants reported higher adaptive coping; participants experiencing persistent poverty or downward mobility reported higher vigilance and avoidant coping and lower adaptive coping. Overall, vigilance was not associated with metabolic risk. Avoidant and adaptive coping were inversely associated with baseline MetS-Z and further varied by sociodemographic factors. Higher adaptive coping was associated with lower MetS-Z among White adults, while higher avoidant coping was associated with lower MetS-Z among Black adults. Lower stress coping were associated with higher MetS-Z among White participants with low lifecourse SES or downward socioeconomic mobility. In sum, stress coping may modulate the stress-health relationship, but these associations must be interpreted within the intersection of contextual factors.