Healthy Aging In Neighborhoods Of Diversity Across The Life Span Research Articles

Examining the Impact of Race and Poverty on the Relationship Between Purpose in Life and Functional Health: Insights from the HANDLS Study.

While research has shown a positive association between a higher sense of purpose in life and functional health, there is a gap in understanding its benefits for racially minoritized and low SES individuals. This study aimed to investigate the correlation between purpose in life and physical functional health in a diverse sample, hypothesizing that purpose in life would be negatively associated with functional difficulties, with potentially stronger associations in White and high SES groups. Data from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study were utilized (166 participants, mean age 59.44 [SD = 8.28], 59.6% females, 65.06% Black participants, 40.36% below poverty). Purpose in life was measured by Ryff's Psychological Well-being Purpose in Life subscale. Functional health was measured by functional difficulties in mobility and daily living. Race (Black and White) and poverty status (above and below) were used as moderators to probe the purpose-functional health association using zero-inflated Poisson regression while adjusting for age, education, depressive symptomology, and previous functional difficulties in four hierarchical models. Results showed that purpose in life was negatively associated with functional difficulty, indicating fewer difficulties in mobility and daily activities among those with a high sense of purpose. While the association did not remain significant after including previous functional difficulty as a covariate in Model 4, suggesting that race may not be a consistent moderator, poverty status remained a consistent moderator. The association was stronger for individuals above the poverty level. These findings underscore the complex interplay between purpose in life, race, poverty status, and functional health, emphasizing the importance of considering socioeconomic factors in interventions aimed at eliminating functional health disparities among diverse adult populations.

Association between Flavonoid Intake and Cognitive Executive Function among African American and White Adults in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) Study.

Healthy dietary patterns rich in flavonoids may benefit cognitive performance over time. Among socioeconomically disadvantaged groups, the association between flavonoid intake and measures of cognition is unclear. This study sought to identify associations between flavonoid intake and cognitive performance among Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study participants (n = 1947) across three study visits. Flavonoid intakes were assessed via two 24-h dietary recalls. Cognitive performance was assessed via the Trail Making Test (TMT)-A and TMT-B, which provide measures of attention and executive function, respectively. Mixed effects linear regression was used to model TMT scores over three study visits against visit 1 (v1) flavonoid intake, time (years from v1), and the interaction between v1 flavonoid intake and time, capturing both the cross-sectional association between flavonoid intake and time at v1 as well as the longitudinal association between v1 flavonoid intake and the change in TMT scores over time. Prior to adjustment, inverse cross-sectional associations at v1 were observed between (1) anthocyanidin intake and TMT-A scores for the overall sample and (2) total flavonoid, anthocyanidin, flavan-3-ol, flavone, and flavonol intake and TMT-B scores for the overall sample and among White adults. Only the association between anthocyanidin intake and TMT-B at v1 among White adults persisted after adjustment (for demographic characteristics such as age). One possible explanation for the few significant associations is universally low flavonoid intakes resulting from the consumption of an unhealthy dietary pattern.

RACE AND SEX DIFFERENCES IN RELATIONS OF DIABETES BIOMARKERS WITH PHYSICAL FUNCTIONING BEFORE DIABETES ONSET

Abstract It remains unclear if declines in physical functioning linked to Type 2 diabetes (T2DM) occur even before T2DM onset. We examined the longitudinal associations of T2DM biomarkers with upper and lower extremity strength among adults without T2DM at baseline. Participants were 1,572 African American (AA) and White adults (M(SD) age at baseline = 47.3 (9.7) years, 55% female, 53% AA) from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, assessed on up to 3 time points between 2004-2017. Participants provided blood samples for measurement of fasting glucose and glycosylated hemoglobin (HbA1c), and completed dominant and nondominant handgrip strength assessment, and a chair stands task to assess upper and lower extremity strength, respectively. Linear mixed effects regression models estimating relations of HbA1c on age-related change and adjusting for race, sex, literacy, and poverty status revealed significant four-way interactions of HbA1c, race, sex, and age (B = -.2.59, t(2853) = -2.0 p = 0.04), and to a lesser extent of fasting glucose, race, sex, and age (B = -.07, t(2863) = -1.84 p = 0.06) on change in the chair stands task, but not on handgrip strength (ps > 0.29). Among younger AA and White men, and younger White women, increasing HbA1c was related to worse lower extremity strength. However, among AA women, and older White women, increasing HBA1c was related to better lower extremity strength. Our findings suggest differential relations of worse glucose regulation on physical functioning amongst African American and White men and women.

BETTER DIET QUALITY IS ASSOCIATED WITH REMAINING NON-FRAIL OVER TIME IN A DIVERSE COHORT

Abstract Frailty is a major public health concern affecting the health and well-being of adults. Poor diet is among several modifiable risk factors for developing frailty. We examined associations of dietary quality assessed by the Healthy Eating Index with frailty status over mean 8.7y follow-up. The sample was comprised of African American (AA) and White participants enrolled in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (44% male, 44% AA, mean baseline age of 48.5y). Only participants from the baseline study and first 2 follow-up visits with dietary data, 2 recall days per visit, and frailty data were included (n=2901). Frailty was prospectively determined by the modified FRAIL scale. Group-based trajectory modeling identified 3 diet quality groups (high: g3 [5.2% of sample, HEI(X±SD): 57.4±4.1], medium (g2: 48.2%, 46.1±3.7), low (g1: 46.5%, 38.2±2.9) and 2 frailty groups (remaining non-frail [20.2% sample] or being pre-frail or frail over time). Multiple logistic and Cox proportional hazards regressions found high and medium HEI trajectory groups, compared to the low HEI group, were associated with reduced risk of being pre-frail or frail, with a clear dose-response relationship (g2 vs. g1: HR=0.77, 95% CI: 0.64-0.92, p=0.004; g3 vs. g1: HR=0.29, 95% CI: 0.18-0.49, P< 0.001), even after adjusting for sociodemographic factors, smoking, drug use, and allostatic load. These findings were corroborated with Kaplan-Meier curves and log-rank tests, providing longitudinal evidence of the link between better diet quality with lower frailty risk, and the importance of diet in successful aging during middle age.

Associations between neighborhood environment and computerized cognitive performance among older Black adults

AbstractBackgroundStudies have suggested that neighborhood quality is associated with health outcomes beyond individuals’ socioeconomic characteristics (Kind & Buckingham, 2018; Ludwig et al., 2011). Limited research has explored how subjective neighborhood quality is associated with cognitive functioning, particularly among socioeconomically diverse Black adults. The current study examined the cross‐sectional association between perceived neighborhood characteristics and cognitive functioning among Black adults.MethodThis study included 1,079 community‐dwelling, socioeconomically diverse Black adults (Mage = 56.64, SDage = 9.14; 59% female) from wave 4 of the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Neighborhood quality was assessed using three scales about built environment disorder (e.g., litter, graffiti, and crime), social cohesion (e.g., close‐knit neighborhood, neighbors can be trusted), and social control (e.g., neighbors take action for children disrespecting adults). Cognitive functioning was assessed using the computerized Joggle battery. Multivariable linear regression analyses were conducted with each cognitive measure as the outcome measure. Models were adjusted for age, sex, education, reading literacy, poverty status, and depressive symptoms.ResultIn the adjusted models, higher built environment disorder was associated with slower performance (p < .05) on an attention and visual orientation measure and fewer correct responses (p’s < .05) on attention, executive function, and speed measures. High social cohesion was associated with faster performance (p < .05) on attention, visual orientation, executive function, and speed measures. Additionally, high social cohesion was associated with greater numbers of correct responses (p < .05) on an attention and executive function measure. Interestingly, high social control was associated with slower performance on executive function. Significant interactions were observed between neighborhood quality and covariates. For example, higher perceived social cohesion was associated with slower average reaction time on memory and attention, particularly for individuals with higher depression total scores. In contrast, higher perceived social cohesion was associated with faster average reaction time on executive functioning, particularly for men.ConclusionThese findings underscore the importance of environmental characteristics for cognitive performance among Black adults. Further, these findings support the continued assessment of contextual factors as mechanisms or avenues for understanding how to improve cognitive functioning.

Associations of AHA’s Life’s Essential 8 health behaviors with cognitive function among U.S. Black and White midlife adults

AbstractBackgroundLife’s Simple 7 (LS7), originally proposed as the seven most important predictors of heart health, is associated with negative cognitive outcomes (Thacker et al., 2014). The recently updated Life’s Essential 8 (LE8) includes sleep. Limited research has investigated the association between LE8 and cognition, particularly within Black and White adults. We hypothesize that higher composite LE8 scores will be associated with better cognitive performance, particularly within Black adults.MethodCross‐sectional analyses were conducted including adults from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study conducted in Baltimore, MD. Study participants (36‐76 years old; 41% male; 61% Black) completed all LE8 (Lloyd‐Jones et al., 2022) and global cognition measurements in wave 4 data collection (2013‐2017). Cognitive performance on a computerized cognitive battery (Joggle Research) yielded a total global cognition score and individual domains (e.g., working memory, attention). Linear regression analyses were stratified by race and poverty status (below 125% Federal poverty guidelines), education attainment (high school), and reading literacy (median split) respectively. Covariates included age, sex, sleep apnea, and depression. All reported models were fully adjusted.ResultAmong Black adults, higher LE8 scores (better CVH) were associated with better working memory only among individuals living above the poverty level (all b unstandardized; b = 0.008, p = .016), or only with high school education (b = 0.009, p = .027). Among White adults, higher LE8 score was associated with better working memory, particularly among individuals living above poverty level (b = 0.014, p = .002), having an education above high school (b = 0.019, p = .002), or high literacy (b = 0.021, p<.001) . Additionally, higher LE8 scores were associated with better attention, and higher global cognition score among individuals living above poverty (b = 0.015, p = .042; b = 0.039, p = .025) or with a high literacy on (b = 0.023, p = .014; b = 0.049, p = .027).ConclusionHigher score of LE8 was associated with better working memory among both U.S. Black and White adults. However, higher LE8 scores were associated with performance across a larger variety of cognitive domains within White adults from diverse socioeconomic indicators. These findings illustrate unique LE8 and cognition associations when disentangling socioeconomic heterogeneity within racial groups.

Plasma neurofilament light and brain volumetric outcomes among middle‐aged urban adults

AbstractBackgroundElevated plasma neurofilament light chain (NfL) is associated with dementia, but the specific underlying mechanisms are largely unknown. We examined cross‐sectional and longitudinal relationships of plasma NfL with selected brain structural magnetic resonance imaging (sMRI) prognostic markers of dementia, namely global and cortical brain, hippocampal and white matter lesion volumes (WMLV).MethodData were extracted from three prospective visits within the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study, selecting participants with complete v1 (2004‐2009) and v2 (2009‐2013) plasma NfL exposure and ancillary sMRI data at vscan (2011‐2015, n = 179, mean v1 to vscan time: 5.4y). Multivariable‐adjusted linear regression models were conducted, overall, by sex, and by race, correcting for multiple testing with q‐values.ResultNfL(v1) (Loge transformed) had a moderately strong association with larger WMLV at follow‐up vscan visit, after a period of 5‐6 years of follow‐up, overall (β = +2.131±0.660, b = +0.29, p = 0.001, q = 0.0029). Moreover, a 1 unit increase in NfLv2 was linked to a left hippocampal volume that was lower by 125 mm3 (p = 0.004, q = 0.015), using minimally adjusted models and mainly among males. Associations were largely unaltered by further adjustment for downstream health‐related factors.ConclusionIn summary, plasma NfL may be an independent medium‐term (within 5 years) marker for increase in WMLV, and a short term (within 1 year) marker for smaller hippocampal volumes normalized to the intracranial volume, independently of other confounding factors. Therefore, plasma NfL holds promise as a blood‐based marker to predict future subclinical brain pathologies in middle‐aged adults.

Pro-Inflammatory Diets Are Associated with Frailty in an Urban Middle-Aged African American and White Cohort.

Diet quality is a modifiable risk factor for frailty, but research on the association of frailty with dietary inflammatory potential is limited. The objective was to determine associations between diet quality assessed by the dietary inflammatory index (DII) with frailty status over time. Participants with both dietary and frailty data from the longitudinal Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study were used (n = 2901, 43.5% male, 43.8% African American, 48.5 y mean baseline age, with a mean 8.7 y of follow-up). Group-based trajectory modeling identified two frailty (remaining non-frail or being pre-frail/frail over time) and three diet quality trajectory groups (high or medium pro-inflammatory and anti-inflammatory potentials). Multiple logistic regression found both medium pro-inflammatory and anti-inflammatory DII trajectory groups, compared to the high pro-inflammatory group, were positively associated with being non-frail over time for the overall sample, both sexes and races. Kaplan-Meier curves and log-rank test revealed anti-inflammatory DII scores were associated with lower risk for being pre-frail or frail. No longitudinal relationship existed between frailty status at baseline and annualized DII change, a check on reverse causality. This study contributes to our current knowledge providing longitudinal evidence of the link between anti-inflammatory DII score with lower frailty risk.

Diet Quality Trajectories over Adulthood in a Biracial Urban Sample from the Healthy Aging in Neighborhoods of Diversity across the Life Span Study.

Limited investigation has been done on diet quality trajectories over adulthood. The main study objectives were to determine the diet quality group trajectories (GTs) over time and to detect changes in a socio-economically and racially diverse middle-aged cohort. Data from three waves of the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study were used to determine diet quality with group-based trajectory modeling (GBTM). Three quality indices-the Healthy Eating Index (HEI), the Dietary Inflammatory Index (DII), and the Mean Adequacy Ratio (MAR)-were explored. The rate of change in quality over time was determined by mixed-effects regression analysis. Three diet quality GTs, low, middle, and high quality, were identified for each index and confirmed with spaghetti plots. Within each GT, only small changes in diet quality scores were observed, with improvements for the HEI and DII indices and a slight decline in MAR scores. Weighted kappa values revealed that the DII had better agreement with the HEI-2010 and MAR indices compared with the agreement between the HEI-2010 and MAR. Bayesian estimates revealed that the annualized rate of change in diet quality per person across the GTs was similar. There was minimal change in diet quality over time, regardless of the diet quality index used.

Coping Behaviors and Incident Kidney Disease.

How someone copes may alter the trajectory of their kidney function. We aimed to evaluate whether coping behaviors were associated with incident chronic kidney disease (CKD) or rapid kidney function decline. We used data from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (Baltimore, MD) for this longitudinal analysis. Adaptive and maladaptive coping behavioral constructs were measured using the Brief COPE Inventory at visit 1. We used multiple logistic regression to assess the odds of incident CKD and rapid kidney function decline per point increase in coping scales and adjusted for baseline demographics and clinical variables. Of 1935 participants, mean age was 48 years, 44% were male, 56% were Black persons, and baseline mean (SD) estimated glomerular filtration rate (eGFR) was 91(16) ml/min/1.73m 2 . After a median of 8.2 years, 113 participants developed incident CKD, and 341 had rapid kidney function decline. Compared to those who reported they usually did not use adaptive coping behaviors at all (such as emotional support), those with the highest use of adaptive coping had lower odds of incident CKD. Every 1-unit increase in adaptive coping corresponded with a 2% lower adjusted odds of incident CKD (OR 0.98, 95% CI 0.95 to 0.99). There was no association between maladaptive coping behaviors and incident CKD. Coping behaviors were not associated with rapid kidney function decline. Adaptive coping behaviors were associated with lower odds of incident CKD and could represent a target to facilitate CKD prevention. The role of medical care in this association is an area worthy of further investigation.

Absent Relations of Religious Coping to Telomere Length in African American and White Women and Men

ABSTRACT Objectives This study investigated whether race and sex moderated the relations of religious coping to telomere length (TL), a biomarker of cellular aging implicated in race-related health disparities. Methods Participant data were drawn from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, which included 252 socioeconomically diverse African American and White men and women aged (30–64 years old). Cross-sectional multivariable regression analyses examined interactive associations of religious coping, race, and sex to TL, adjusting for other sociodemographic characteristics. Results Religious coping was unrelated to TL in this sample (p’s > .05). There were no notable race or sex differences. Post hoc exploratory analyses similarly found that neither secular social support coping use nor substance use coping was associated with TL. Conclusion There was no evidence to support that religious coping use provided protective effects to TL in this sample of African American and White women and men. Nevertheless, future studies should use more comprehensive assessments of religious coping and intersectional identities to provide an in-depth examination of religiosity/spirituality as a potential culturally salient protective factor in cellular aging among African Americans in the context of specific chronic stressors such as discrimination.

0853 Neighborhood disorder and pain: The mediating role of sleep

Abstract Introduction Neighborhood factors are related to poor sleep, and sleep problems are known to have a strong relationship with pain. The underlying mechanisms for this association remain unclear. The present study evaluated whether sleep duration, sleep quality, or global sleep quality mediated the relation between perceived Neighborhood Disorder (ND) and pain intensity or interference. The study also explored whether adjusting for depressive symptoms accounted for significant mediational pathways found in Aim 1. Methods Participants were drawn from Wave 4 (September 2013 to September 2017) of the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) epidemiologic cohort study (n=1,071). Perceived ND was measured using the HANDLS Neighborhood Problems Scale, which assesses how often a particular neighborhood problem occurs. The Patient Reported Outcomes Measurement Information System Pain Intensity short form 3a was used to assess how much a person hurt in the past 7 days, and pain interference was measured by the bodily pain subdomain of the 12-item Short-Form Health Survey. The Pittsburgh Sleep Quality Index was used to assess sleep duration, subjective sleep quality, and global sleep quality. Results Results of the study revealed mediating effects of global sleep quality on the relation of perceived ND and pain intensity (indirect effect = .5527, SE =.1355, 95% CI [.2914, .8316]) and pain interference (indirect effect = .0579 (SE = .0143), 95% CI [.0312, .0876]) and also of subjective sleep quality on pain intensity (indirect effect = .5801, SE =.1337, 95% CI [.3206, .8468]) and pain interference (indirect effect = .0587 (SE =.0137), 95% CI [.0327, .0867]). Results revealed that mediating effects of sleep quality and global sleep on the relation of perceived ND and pain intensity and pain interference remained significant after adjustment for depressive symptoms. Conclusion These findings provide preliminary evidence to support the notion that select sleep dimensions, particularly sleep quality, is a pathway by which subjective neighborhood factors may impact pain intensity and pain interference. More research is needed to understand potential pathways underlying the perceived ND and pain relation. Support (if any) NIH Intramural Research Program Inter-laboratory proposal provided by the National Institute on Aging Intramural Research Program

0087 Associations between AHA’s Life’s Essential 8 and cognition in a sample of diverse midlife adults

Abstract Introduction Life’s Simple 7 (LS7), originally proposed as the seven most important predictors of heart health, is associated with negative cognitive outcomes. Recently an updated Life’s Essential 8 (LE8) added sleep as the new eighth component. However, limited research has investigated LE8 and cognitive outcomes. We hypothesize that a higher composite LE8 score will be associated with better cognitive performance. Methods Cross-sectional analyses were conducted including 1498 adults (36-76 years old, 41% male, 61% African American) from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study who completed all LE8 and global cognition measurements in wave 4 data collection (2013-2017). Blood pressure, glucose, cholesterol, BMI, diet, physical activity, and smoking were calculated based on available wave 4 data per LE8 scoring guidance. The sleep component was scored based on the sleep duration question from the Pittsburgh Sleep Quality Index (“During the past month, how many hours of actual sleep did you get at night?”). LE8 score was calculated by averaging the scores from the eight components. Cognitive performance was measured from a Joggle battery to calculate a total global cognition score and individual domains (memory, attention, visual orientation, executive function, speed). A set of linear regression analyses were performed. Covariates included biological age, sex, race, poverty status, sleep apnea, education attainment (high school), reading literacy, and depression (CES-D). Results Higher scores on LE8 were significantly associated with better global cognitive performance, even after adjusting for covariates (b=0.024, p = .014). Among all cognitive domains, higher LE8 scores were significantly associated with better memory (b = 0.011, p < .001), attention (b=0.012, p = .007), but not visual orientation, executive function, or speed. Conclusion Better cardiovascular health, as indicated by a higher LE8 composite score, is associated with better cognitive performance among U.S. middle-aged and older adults. Future studies may further explore this relationship using longitudinal data and explore the predictive power of each LE8 component. Support (if any) UF1AG072619 (PI: Gamaldo)

Trajectories in allostatic load as predictors of sleep quality among urban adults: Healthy aging in neighborhoods of diversity across the life span study

Objective/Background: The allostatic framework is a theoretical perspective that identifies allostatic load (AL) as a meaningful measure of dysregulation and desynchrony across biological processes due to cumulative stress exposure, thereby increasing disease risk. Research exploring the relationships of AL with sleep quality have yielded inconsistent findings. We examined AL at three visits (2004–2009 [Visit 1], 2009–2013 [Visit 2] and 2013–2017 [Visit 3]) in relation to sleep quality [Visit 3] among urban adults by sex, race and age group. Patients/methodsWe analyzed data on 1489 Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) participants [59.6% female, baseline age: 48.2 years, 58.5% African Americans] with available data on cardiovascular, metabolic and inflammatory AL markers and Pittsburgh Sleep Quality Index (PSQI) scores. Least squares regression models were constructed to evaluate AL score at Visit 1 (ALv1) and z-transformed probability of higher trajectory in AL score between Visit 1 and Visit 3 (ALtraj) as predictors of PSQI score at Visit 3, controlling for demographic, lifestyle and health characteristics at Visit 1. ALtraj was generated using group-based trajectory modeling. ResultsIn fully adjusted models, ALv1 and PSQI score were positively related among men only (β = 0.43, P = 0.001), whereas higher ALtraj was associated with PSQI score among women (β = 0.51, P = 0.001), White (β = 0.45, P = 0.011) and African American (β = 0.33, P = 0.014) populations. There were no statistically significant interactions according to age group (<50 vs. ≥ 50). ConclusionsDisparities exist whereby AL trajectory predicted sleep quality among women irrespective of race and baseline AL predicted sleep quality among men. Future studies should examine bi-directional AL-sleep relationships.

Plasma neurofilament light and brain volumetric outcomes among middle-aged urban adults

Elevated plasma neurofilament light chain (NfL) is associated with dementia though underlying mechanisms remain unknown. We examined cross-sectional relationships of time-dependent plasma NfL with selected brain structural magnetic resonance imaging (sMRI) prognostic markers of dementia. The sample was drawn from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study, selecting participants with complete v1 (2004–2009) and v2 (2009–2013) plasma NfL exposure and ancillary sMRI data at vscan (2011–2015, n = 179, mean v1 to vscan time: 5.4 years). Multivariable-adjusted linear regression models were conducted, overall, by sex, and race, correcting for multiple testing with q-values. NfL(v1) was associated with larger WMLV (both Loge transformed), after 5–6 years’ follow-up, overall (β = +2.131 ± 0.660, b = +0.29, p = 0.001, and q = 0.0029) and among females. NfLv2 was linked to a 125 mm3 lower left hippocampal volume (p = 0.004 and q = 0.015) in reduced models, mainly among males, as was observed for annualized longitudinal change in NfL (δNfLbayes). Among African American adults, NfLv1 was inversely related to total, gray and white matter volumes. Plasma NfL may reflect future brain pathologies in middle-aged adults.

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.

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.

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.

GDF15 and its association with cognitive performance over time in a longitudinal study of middle-aged urban adults

Serum GDF15 levels are correlated with multiple neurodegenerative diseases. Few studies have tested this marker’s association with middle-aged cognitive performance over time, and whether race affects this association is unknown. We examined associations of initial serum GDF15 concentrations with longitudinal cognitive performance, spanning domains of global mental status, visual and verbal memory, attention, fluency, and executive function in a sub-sample of adults participating in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (n = 776, Agev1:30-66y, 45.6 % male, 57.0 % African American, 43.0 % below poverty). This analysis consisted of mixed-effects regression models applied to the total selected sample, while also stratifying the analyses by race in the main analyses and further stratifying by sex, age group and poverty status in an exploratory analysis. Our main findings, which passed multiple testing and covariate-adjustment, indicated that GDF15 was associated with poorer baseline performance on several cognitive tests, including animal fluency [overall sample: (Model 1: γ0 ± SE: −0.664 ± 0.208, P < 0.001; Model 2, γ0 ± SE: −0.498 ± 0.217, P < 0.05)]. Among White adults, GDF15 was linked to poorer performance on a brief test of attention (Model 1: γ0 ± SE: −0.426 ± 0.126, P < 0.001; Model 2, γ0 ± SE: −0.281 ± 0.139, P < 0.05); and Trailmaking test, part B (Model 1: γ0 ± SE: +0.129 ± 0.040, P < 0.001; Model 2, γ0 ± SE: +0.089 ± 0.041, P < 0.05), the latter being also linked to higher GDF15 among individuals living below poverty. Among women, GDF15 was associated with poor global mental status (Normalized MMSE: Model 1: γ0 ± SE: −2.617 ± 0.746, P < 0.001; Model 2: γ0 ± SE: −1.729 ± 0.709, P < 0.05). GDF15 was not associated with decline on any of the 11 cognitive test scores considered in ∼ 4 years of follow-up. In sum, we detected cross-sectional associations between GDF15 and cognition, although GDF15 did not predict rate of change in cognitive performance over time among a sample of middle-aged adults. More longitudinal studies are needed to address the clinical utility of this biomarker for early cognitive defects.

White matter integrity as a mediator between socioeconomic status and executive function.

Lower socioeconomic status (SES) is associated with poorer executive function, but the neural mechanisms of this association remain unclear. As healthy brain communication is essential to our cognitive abilities, white matter integrity may be key to understanding socioeconomic disparities. Participants were 201 African American and White adults (ages 33-72) from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) SCAN study. Diffusion tensor imaging was used to estimate regional fractional anisotropy as a measure of white matter integrity. Adjusting for age, analyses examined if integrity of the anterior limb of the internal capsule (ALIC), external capsule (EC), superior longitudinal fasciculus (SLF), and cingulum mediated SES-executive function relations. Lower SES was related to poorer cognitive performance and white matter integrity. Lower Trails B performance was related to poorer integrity of the ALIC, EC, and SLF, and lower Stroop performance was associated with poorer integrity of the ALIC and EC. ALIC mediated the SES-Trails B relation, and EC mediated the SES-Trails B and SES-Stroop relations. Sensitivity analyses revealed that (1) adjustment for race rendered the EC mediations non-significant, (2) when using poverty status and continuous education as predictors, results were largely the same, (3) at least some of the study's findings may generalize to processing speed, (4) mediations are not age-dependent in our sample, and (5) more research is needed to understand the role of cardiovascular risk factors in these models. Findings demonstrate that poorer white matter integrity helps explain SES disparities in executive function and highlight the need for further clarification of the biopsychosocial mechanisms of the SES-cognition association.