This study examines the association between DNA methylation-based epigenetic aging indices and neurofilament light chain levels in middle-aged African Americans to advance the understanding of neurodegeneration and cognitive decline. Epigenetic aging was assessed in samples from 2008 and 2019 by applying HorvathAgeAccel, HannumAgeAccel, PhenoAgeAccel, GrimAgeAccel, and DunedinPACE. Controlling for financial strain, exercise, age, gender, cell-type composition, and APOE-ε4, second- and third-generation DNA methylation-based aging-PhenoAgeAccel, GrimAgeAccel, and DunedinPACE-were significantly associated with serum neurofilament light chain levels. In contrast, first-generation DNA methylation-based clocks, including HorvathAgeAccel and HannumAgeAccel, were not significantly related to neurofilament light chain. These findings suggest that newer DNA methylation-based aging indices are more strongly associated with neurodegenerative biomarkers. Integrating advanced DNA methylation-based clocks with neurofilament light chain levels may improve early detection of cognitive decline and dementia, supporting personalized medicine by identifying biological aging profiles linked to neurodegenerative risks.

BackgroundCompared to other racial/ethnic groups, Black Americans show accelerated brain aging beginning in midlife and exhibit higher rates and earlier onset of dementia. While these patterns are often viewed as evidence that Black Americans are more vulnerable to Alzheimer's disease, another possibility is that their high risk for chronic vascular pathologies such as high blood pressure and diabetes compromises their brain health. This hypothesis was tested in the present study.MethodsParticipants included 252 middle-aged Black Americans enrolled in the Family and Community Health Study and living in Iowa or Georgia who had ascertainment of diabetes and hypertension in 2008 and blood drawn in 2008 and 2019. Linear regression models assessed whether hypertension and diabetes were associated with change in neurofilament light chain (NfL), a non-specific biomarker of brain pathology including vascular dementia, and phosphorylated tau181 (p-Tau181), a biomarker of underlying Alzheimer's disease (AD) pathology.ResultsHaving a diagnosis of either hypertension or diabetes during middle age was not associated with levels of either p-Tau181 or NfL. However, having a diagnosis of both hypertension and diabetes was robustly associated with higher levels of NfL and increases in NfL over an 11-year period.ConclusionsAmong Black Americans, comorbid hypertension and diabetes contribute to higher levels of serum NfL, our indicator of neurodegeneration, during late middle age but not with p-Tau181, our indicator of Alzheimer's disease. Rather than being instances of AD, elevated rates of dementia among Black Americans may be largely vascular pathology caused by high rates of diabetes and high blood pressure.

BACKGROUND AND OBJECTIVES:African American individuals have a higher risk of Alzheimer disease (AD) and related dementia (ADRD) than non-Hispanic White individuals. Some cross-sectional studies with self-reported race and ethnicity have reported racial differences in circulating ADRD biomarkers, including phosphorylated tau181 (p-Tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). We aimed to examine the associations of genetically inferred African ancestry proportion with the longitudinal changes in these biomarkers and to evaluate the associations of previously identified ADRD-related genetic factors in European cohorts with these biomarkers in an African American cohort. METHODS:This study used longitudinal data from the Family and Community Health Study, which was initiated in 1996, recruited and followed 889 African American families residing in Georgia and Iowa. Circulating p-Tau181, GFAP, and NfL were measured in serum samples collected in 2008 (wave 5) and 2019 (wave 8). Closely related individuals, genetically inferred to be third-degree relatives or closer, were excluded. Genetic ancestry proportions were inferred using the ADMIXTURE analysis. Multivariable regression analyses were performed to test the associations of African ancestry proportion with cross-sectional biomarker levels and their longitudinal changes over 11 years. We also tested the associations of selected genetic variants, polygenic scores, and APOE ε4 status with these biomarkers. RESULTS:Our cross-sectional sample included 573 participants (mean age = 55.1 years; 69% female), whereas our longitudinal sample included 225 (57.2 years; 80% female). African ancestry proportion was not associated with cross-sectional biomarker levels but was inversely associated with the longitudinal change in p-Tau181 (β = -14.50 pg/mL, p = 0.02). The significant inverse association was robust to adjustment for age, sex, APOE ε4, socioeconomic status, physical activity, smoking, subjective cognitive decline, and various cardiovascular risk factors and comorbidities. Finally, genetic factors associated with AD and biomarkers in European cohorts were not associated with the 3 biomarkers in our African American cohort. DISCUSSION:We found suggestive evidence that a higher African ancestry proportion is associated with an attenuated increase in the blood p-Tau181 level over time. More research is needed to characterize the longitudinal dynamics of ADRD biomarkers across ancestry and the driving biological or sociocultural factors.

Using the dual-pathway framework (Beach et al., 2022a), we tested a Neuro-immune Network (NIN) hypothesis: i.e., that chronically elevated inflammatory processes may have delayed (i.e., incubation) effects on young adult substance use, leading to negative health outcomes. In a sample of 449 participants in the Family and Community Health Study who were followed from age 10 to age 29, we examined a non-self-report index of young adult elevated alcohol consumption (EAC). By controlling self-reported substance use at the transition to adulthood, we were able to isolate a significant delayed (incubation) effect from childhood exposure to danger to EAC (β = −.157, p = .006), which contributed to significantly worse aging outomes. Indirect effects from danger to aging outcomes via EAC were: GrimAge (IE = .010, [.002, .024]), Cardiac Risk (IE = −.004, [−.011, −.001]), DunedinPACE (IE = .002, [.000, .008]). In exploratory analyses we examined potential sex differences in effects, showing slightly stronger incubation effects for men and slightly stronger effects of EAC on aging outcomes for women. Results support the NIN hypothesis that incubation of immune pathway effects contributes to elevated alcohol consumption in young adulthood, resulting in accelerated aging and elevated cardiac risk outcomes via health behavior.

Objectives: The study draws upon perspectives on life-course stressors and health to assess whether lifetime incarceration exposure is a determinant of biological aging and self-reported depression. Methods: Using data from a sample of 460 African American participants (average age= 57) in the Family and Community Health Study, the study examined two epigenetic indices of biological aging, DunedinPoAm and GrimAge, as well as a self-reported measure of depression symptoms. Estimates were derived from multivariate regression models with adjustments for selection on observables and confounding factors. Results: Exposure to incarceration was a significant determinant of accelerated biological aging (GrimAge) and the pace of aging (DunedinPoAm) and depressive symptoms. Discussion: Among formerly incarcerated older adults, past experiences with the stressors of incarceration predict key biomarkers of physiological deterioration and depressive symptoms. Incarceration contributes to the mental and physical health burden of older adults.

INTRODUCTION:Recent evidence suggests that exposure to the stress of racism may increase the risk of dementia for Black Americans. METHODS:The present study used 17 years of data from a sample of 255 Black Americans to investigate the extent to which exposure to racial discrimination predicts subsequent changes in serum Alzheimer's Disease Research Center (ADRC) biomarkers: serum phosphorylated tau181(p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP). We hypothesized that racial discrimination assessed during middle age would predict increases in these serum biomarkers as the participants aged into their 60s. RESULTS:Our findings indicate that exposure to various forms of racial discrimination during a person's 40s and early 50s predicts an 11-year increase in both serum p-tau181 and NfL. Racial discrimination was not associated with subsequent levels of GFAP. DISCUSSION:These findings suggest that racial discrimination in midlife may contribute to increased AD pathology and neurodegeneration later in life. HIGHLIGHTS:A 17-year longitudinal study of Black Americans. Assessments of change in serum p-tau181, neurofilament light, and glial fibrillary acidic protein. Exposure to racial discrimination during middle age predicted increases in p-tau181 and neurofilament light. Education was positively related to both p-tau181 and exposure to racial discrimination.

Background This study examined the longitudinal relationship between cumulative socioeconomic status (SES) risk and serum neurofilament light chain (NfL) levels to better understand the association between social factors and a biomarker of neurodegeneration.Methods We used data from the Family and Community Health Study, collecting psychosocial and blood data at 2 waves (2008) and (2019) from 254 Black Americans (43 males and 211 females). Blood samples were analyzed at each wave for serum NfL concentrations. Regression analysis and mixed-effect modeling examined relationships between cumulative SES risk and serum NfL, controlling for covariates and assessing time effects.Results Utilizing 11-year longitudinal data, serum NfL levels increased with age. Higher cumulative SES risk at baseline correlated with elevated serum NfL at the 11-year follow-up and predicted a greater increase in NfL levels. Clinically, NfL is a sensitive biomarker for axonal injury and neurodegeneration, commonly used to detect early and preclinical stages of conditions such as Alzheimer's disease, multiple sclerosis, and other neurodegenerative disorders.Conclusions Our results suggest that exposure to cumulative SES risk among Black adults may contribute to elevated levels of NfL, indicating potential early neurodegeneration. Given the established role of NfL in detecting neurodegenerative processes, these findings underscore the importance of interventions that bolster social safety nets and social connectedness to enhance brain health and mitigate neurodegenerative risks.

Objectives Recent studies show that chronic exposure to racial discrimination increases the occurrence of subjective cognitive decline (SCD) among Black Americans. Little research, however, has examined potential for protective factors, such as perceived partner support, to buffer these effects. Methods This study utilized longitudinal data over a 10-year period from the Family and Community Health Study (FACHS) to examine the associations between experiences of racial discrimination, marital status, partner support, and SCD, measured by the Everyday Cognition (ECog) Scale, among 286 middle-aged Black American women. Regression analysis and internal moderator analyses were employed to analyze the data. Results About 31% were in married relationships. Thirty-four percent reported cognitive decline, especially in forgetting object locations and dates. Chronic discrimination predicted SCD, and for those in couple relationships, partner support buffered the adverse effects of discrimination, with those in warm and supportive relationships experiencing less SCD than those in relatively unsupportive relationships or not in a relationship. Conclusions The study's findings support the idea that racism influences SCD and underscores the importance of supportive couple relationships in promoting resilience. The results also highlight the potential value of culturally relevant family interventions and support strategies to reduce the impact of discrimination-induced stress on cognitive health.

A recent epigenetic measure of aging has developed based on human cortex tissue. This cortical clock (CC) dramatically outperformed extant blood-based epigenetic clocks in predicting brain age and neurological degeneration. Unfortunately, measures that require brain tissue are of limited utility to investigators striving to identify everyday risk factors for dementia. The present study investigated the utility of using the CpG sites included in the CC to formulate a peripheral blood-based cortical measure of brain age (CC-Bd). To establish the utility of CC-Bd, we used growth curves with individually varying time points and longitudinal data from a sample of 694 aging African Americans. We examined whether three risk factors that have been linked to cognitive decline—loneliness, depression, and BDNFm—predicted CC-Bd after controlling for several factors, including three new-generation epigenetic clocks. Our findings showed that two clocks—DunedinPACE and PoAm—predicted CC-BD, but that increases in loneliness and BDNFm continued to be robust predictors of accelerated CC-Bd even after taking these effects into account. This suggests that CC-Bd is assessing something more than the pan-tissue epigenetic clocks but that, at least in part, brain health is also associated with the general aging of the organism.

Objective:The purpose of this study was to assess the impact of perceived racial discrimination on the satisfaction and dissolution of different-gender, nonmarital relationships among African American young adults.Background:Racial discrimination has proven detrimental to relationship quality among married couples. Racial disparities in relationship processes begin long before marriages form, however. Racial discrimination may also weather and disrupt nonmarital relationships earlier in the life course.Method:Survey data from African American young adult couples (N = 407) from the Family and Community Health Study were used to assess the associations between each partner's experience of racial discrimination, relationship satisfaction, and relationship dissolution using structural equation modeling.Results:Results support a stress spillover perspective in that racial discrimination experienced by both men and women increased the likelihood of relationship dissolution through reduced satisfaction. No support was found for a stress buffering perspective.Conclusion:Racial discrimination appears to distress and, ultimately, disrupt nonmarital relationships among African American young adult couples.Implications:Given the role of relationship quality and stability in promoting health and well-being, understanding how discrimination impacts the unfolding of relationships, or linked lives, across the life course is essential to untangling and addressing the "chains of disadvantage" identified by Umberson et al. (2014) as central to racial disparities in health and well-being.

Objectives The present study builds on recent findings suggesting that the stress of institutional and interpersonal racism may contribute to African Americans' elevated risk for dementia. We investigated the extent to which 2 consequences of racism-low socioeconomic status (SES) and discrimination-predict self-reported cognitive decline (SCD) 19 years later. Further, we examined potential mediating pathways that might link SES and discrimination to cognitive decline. Potential mediators included depression, accelerated biological aging, and onset of chronic illnesses. Methods Hypotheses were tested using a sample of 293 African American women. SCD was assessed using the Everyday Cognition Scale. Structural equation modeling was used to assess the effects of SES and racial discrimination, both measured in 2002, on SCD reported in 2021. Turning to the mediators, midlife depression was assessed in 2002, accelerated aging in 2019, and chronic illness in 2019. Age and prodrome depression were included as covariates. Results There were direct effects of SES and discrimination on SCD. In addition, these 2 stressors showed a significant indirect effect on SCD through depression. Finally, there was evidence for a more complex pathway where SES and discrimination accelerate biological aging, with accelerated aging, in turn leading to chronic illness, which then predicted SCD. Discussion Results of the present study add to a growing literature indicating that living in a racialized society is a central factor in explaining the high risk for dementia among Black Americans. Future research should continue to emphasize the various ways that exposure to racism over the life course effects cognition.

Abstract Background Social scientists generally agree that health disparities are produced, at least in part, by adverse social experiences, especially during childhood and adolescence. Building on this research, we use an innovative method to measure early adversity while drawing upon a biopsychosocial perspective on health to formulate a model that specifies indirect pathways whereby childhood and adolescent adversity become biologically embedded and influence adult health. Method Using nearly 20 years of longitudinal data from 382 Black Americans, we use repeated-measures latent class analysis (RMLCA) to construct measures of childhood/adolescent adversities and their trajectories. Then, we employ structural equation modeling to examine the direct and indirect effects of childhood/adolescent adversity on health outcomes in adulthood through psychosocial maladjustment. Results RMLCA identified two classes for each component of childhood/adolescent adversity across the ages of 10 to 18, suggesting that childhood/adolescent social adversities exhibit a prolonged heterogeneous developmental trajectory. The models controlled for early and adult mental health, sociodemographic and health-related covariates. Psychosocial maladjustment, measured by low self-esteem, depressive and anxiety symptoms, and lack of self-control, mediated the relationship between childhood/adolescent adversity, especially parental hostility, racial discrimination, and socioeconomic class, and both self-reported illness and blood-based accelerated biological aging (with proportion mediation ranging from 8.22% to 79.03%). Conclusion The results support a biopsychosocial model of health and provide further evidence that, among Black Americans, early life social environmental experiences, especially parenting, financial stress, and racial discrimination, are associated with adult health profiles, and furthermore, psychosocial mechanisms mediate this association.

Existing research demonstrates that racial discrimination negatively affects life outcomes for Black Americans. Yet, it is unknown how exposure to racial discrimination changes over time. To address this gap, we (1) assess the pattern of experiences with racial discrimination from age 10 to 30; (2) test how exposure to discrimination changes within childhood, adolescence, and adulthood; and (3) analyze factors associated with experiencing racial discrimination over time. To accomplish this, we use seven waves of the Family and Community Health Study, a longitudinal data set of Black Americans. We observe a curvilinear relationship between discrimination and age such that exposure initially increases in childhood, peaks in adolescence, then declines in adulthood. Using piecewise growth modeling, we find support for this pattern, marking the period from childhood to adolescence as a critical time period. Finally, factors such as geographical location, criminal justice involvement, and attending college are associated with experiencing greater racial discrimination.

Type 2 diabetes mellitus (T2D) has a complex genetic and environmental architecture that underlies its development and clinical presentation. Despite the identification of well over a hundred genetic variants and CpG sites that associate with T2D, a robust biosignature that could be used to prevent or forestall clinical disease has not been developed. Based on the premise that underlying genetic variation influences DNA methylation (DNAm) independently of or in combination with environmental exposures, we assessed the ability of local and distal gene x methylation (GxMeth) interactive effects to improve cg19693031 models for predicting T2D status in an African American cohort. Using genome-wide genetic data from 506 subjects, we identified a total of 1476 GxMeth terms associated with HbA1c values. The GxMeth SNPs map to biological pathways associated with the development and complications of T2D, with genetically contextual differences in methylation observed only in diabetic subjects for two GxMeth SNPs (rs2390998 AG vs. GG, p = 4.63 × 10−11, Δβ = 13%, effect size = 0.16 [95% CI = 0.05, 0.32]; rs1074390 AA vs. GG, p = 3.93 × 10−4, Δβ = 9%, effect size = 0.38 [95% CI = 0.12, 0.56]. Using a repeated stratified k-fold cross-validation approach, a series of balanced random forest classifiers with random under-sampling were built to evaluate the addition of GxMeth terms to cg19693031 models to discriminate between normoglycemic controls versus T2D subjects. The results were compared to those obtained from models incorporating only the covariates (age, sex and BMI) and the addition of cg19693031. We found a post-pruned classifier incorporating 10 GxMeth SNPs and cg19693031 adjusted for covariates predicted the T2D status, with the AUC, sensitivity, specificity and precision of the positive target class being 0.76, 0.81, 0.70 and 0.63, respectively. Comparatively, the AUC, sensitivity, specificity and precision using the covariates and cg19693031 were only 0.71, 0.74, 0.67 and 0.59, respectively. Collectively, we demonstrate correcting for genetic confounding of cg19693031 improves its ability to detect type 2 diabetes. We conclude that an integrated genetic–epigenetic approach could inform personalized medicine programming for more effective prevention and treatment of T2D.

Early experiences of school disengagement may serve as a warning sign for later young adult adjustment difficulties and eventually contribute to accelerated aging among Black American youth. At the same time, supportive parenting may play a protective role. Using longitudinal data from the Family and Community Health Study (FACHS), we examined psychological maladjustment (comprising depression, lack of self-regulation, and low self-esteem) as a mediator of the relationship between school disengagement and accelerated aging. We also examined the effect of supportive parenting in buffering the impact of school disengagement on adulthood outcomes by controlling for covariates. Hypotheses were examined in a sample of 386 (Mean age = 28.68; Females = 62.7%; Males = 37.3%) Black American youth who were followed into young adulthood. Path modeling was used to test hypothesized relationships. We found school disengagement, i.e., problems with school attendance, performance, and engagement, reported across ages 10–18, predicted psychological maladjustment, which, in turn, predicted accelerated aging at age 29. We also found a buffering effect for supportive parenting. No significant gender difference in the indirect effect or buffering effect was found. This study highlights the potential importance of greater attention to school disengagement to identify and potentially influence long-term health trajectories and adult outcomes for Black American youth.

In a sample of 685 late middle-aged Black adults (M age at 2019 = 57.17 years), we examined the effects of loneliness and per capita income on accelerated aging using a newly developed DNA-methylation based index: the DunedinPACE. First, using linear, mixed effects regression in a growth curve framework, we found that change in DunedinPACE was dependent on age, with a linear model best fitting the data (b = 0.004, p < 0.001), indicating that average pace of change increased among older participants. A quadratic effect was also tested, but was non-significant. Beyond the effect of age, both change in loneliness (b = 0.009, p < 0.05) and change in per capita income (b = −0.016, p < 0.001) were significantly associated with change in DunedinPACE across an 11-year period, accounting for significant between person variability observed in the unconditional model. Including non-self-report indices of smoking and alcohol use did not reduce the association of loneliness or per capita income with DunedinPACE. However, change in smoking was strongly associated with change in DunedinPACE such that those reducing their smoking aged less rapidly than those continuing to smoke. In addition, both loneliness and per capita income were associated with DunedinPACE after controlling for variation in cell-types.

OBJECTIVE:Research has implicated incarceration exposure as a social determinant of health, with recent work suggesting incarceration may trigger a stress response that accelerates physiological deterioration. The objective of the current study is to assess whether neighborhood stressors intensify the health consequences of incarceration exposure.METHODS:We test whether two neighborhood context measures - socioeconomic disadvantage and perceived crime - moderate the association between incarceration exposure and a measure of accelerated epigenetic aging based on the GrimAge index. Our sample included 408 African American young adults from the Family and Community Health study.RESULTS:Results from regression analyses with inverse probability of treatment weights suggest that incarceration exposure and neighborhood disadvantage are independently associated with accelerated biological aging. The results also show that the impact of incarceration exposure on accelerated aging is amplified for individuals in neighborhoods with higher levels of perceived crime.CONCLUSIONS:These findings indicate that the neighborhood contexts where formerly incarcerated individuals return have a substantial impact on their pace of biological aging. Policies aimed at reducing ambient stressors after release may promote healthy aging among formerly incarcerated African American adults.

The steeling hypothesis suggests experiencing moderate strain may improve an individual's ability to cope with future strain, whereas crisis theory suggests that experiencing temporary strain will reduce the effect of future strain. The current study improves on past research by utilizing data from two independent prospective panel studies (one of 553 white rural Midwesterner women and 451 men and one of 624 African American women) spanning 26 and 22 years, respectively. We utilize growth mixture modeling to identify latent groups based on trajectories of financial strain and test interactions between class membership and later acute stressful events on chronic illness and physical health using three subscales from the RAND SF-12. We find being a group that experienced a period of temporary strain weakened the effect of later acute stressors on physical health for both samples and chronic illness for the African American sample. Results support crisis theory and highlight the importance of considering chronic strain as a life course process.

OBJECTIVES:Past research has established a link between romantic relationships and depressive symptoms among adults, including those in later life. There is, however, still a lack of evidence regarding whether romantic relationship status or relationship quality is a better predictor of psychological well-being among middle-aged and older Black adult women.METHODS:The present study draws on data from the Family and Community Health Study, a multisite, longitudinal survey of health and psychosocial experiences of Black families, to examine how relationship status and quality relate to depressive symptoms among middle-aged and older Black adult women (N = 571). A series of negative binomial regression models, with 95% confidence intervals and internal moderators, were used to assess the research questions.RESULTS:Middle-aged and older Black women in married, cohabiting, and dating relationships who reported higher levels of relationship quality had a lower likelihood of depressive symptoms than those who reported lower levels of relationship quality or who did not report being in any romantic relationship when controlling for baseline depressive symptoms. The findings from our study indicate that relationship quality is a better predictor of depressive symptoms than relationship status.DISCUSSION:Our findings extend the body of literature on the impact of romantic relationships on individual well-being and provide compelling evidence that such relationships, particularly those of high quality, are significantly associated with lower depressive symptoms among middle-aged and older Black women.

Methylation of FKBP5 is involved in the regulation of the stress response and is influenced by early stress exposure. Two CpG sites, cg20813374 and cg00130530, have been identified as potential reporters of early stress. We examined whether FKBP5 methylation was associated with accelerated DNA methylation ageing and indirectly predicted poorer cardiovascular health among both young adult and middle-aged Black Americans. Four hundred and forty-nine young adults, with a mean age of 28.67 and N = 469 middle-age parents and their current partners with a mean age of 57.21, provided self-reports, biometric assessments, and blood draws. Methylation values were obtained using the Illumina Epic Array. Cardiometabolic risk was calculated by summing the standardized log-transformed scores for the body mass index, mean arterial blood pressure, and HbA1c. We also used a more standard index of risk, the Framingham 10-year cardiometabolic risk index, as an alternative measure of cardiometabolic risk. To measure accelerated ageing, four widely used indices of accelerated, DNA methylation-based ageing were used controlling sex, age, other variation in FKBP5, and cell-type. Exposure to community danger was associated with demethylation of FKBP5. FKBP5 methylation was significantly associated with accelerated ageing for both young-adult and middle-aged samples, with significant indirect effects from FKBP5 methylation to cardiometabolic risk through accelerated ageing for both. Early exposure to danger may influence FKBP5 methylation. In turn, FKBP5 methylation may help explain intrinsic accelerated ageing and elevated cardiometabolic risk in adulthood for Black Americans.