"Hang Ups, Let Downs, Bad Breaks, Setbacks": Impact of Structural Socioeconomic Racism and Resilience on Cognitive Change Over Time for Persons Racialized as Black.

Introduction: Older adults racialized as Black experience higher rates of dementia than those racialized as White. Structural racism produces socioeconomic challenges, described by artist Marvin Gaye as "hang ups, let downs, bad breaks, setbacks" that likely contribute to dementia disparities. Robust dementia literature suggests socioeconomic factors may also be key resiliencies. Methods: We linked state-level data reflecting the racialized landscape of economic opportunity across the 20th Century from the U.S. Census (1930-2010) with individual-level data on cognitive outcomes from the U.S. Health and Retirement Study participants racialized as Black. A purposive sample of participants born after the Brown v. Board ruling (born 1954-59) were selected who completed the modified Telephone Interview for Cognitive Status between 2010 and 2020 (N=1381). We tested associations of exposure to structural racism and resilience before birth, and during childhood, young-adulthood, and midlife with cognitive trajectories in mid-late life using mixed-effects regression models. Results: Older adults born in places with higher state-level structural socioeconomic racism experienced a more rapid cognitive decline in later life compared to those with lower levels of exposure. In addition, participants born in places with higher levels of state-level structural socioeconomic resilience experienced slower cognitive change over time than their counterparts. Discussion: These findings reveal the impact of racist U.S. policies enacted in the past that influence cognitive health over time and dementia risk later in life.

Racial and ethnic differences in the association between depressive symptoms and cognitive outcomes in older adults: Findings from KHANDLE and STAR.

INTRODUCTION: Depressive symptoms are associated with higher risk of dementia, but how they impact cognition in diverse populations is unclear. METHODS: Asian, Black, Latino, or White participants (n = 2227) in the Kaiser Healthy Aging and Diverse Life Experiences (age 65+) and the Study of Healthy Aging in African Americans (age 50+) underwent up to three waves of cognitive assessments over 4 years. Multilevel models stratified by race/ethnicity were used to examine whether depressive symptoms were associated with cognition or cognitive decline and whether associations differed by race/ethnicity. RESULTS: Higher depressive symptoms were associated with lower baseline verbal episodic memory scores (-0.06, 95% CI: -0.12, -0.01; -0.15, 95% CI: -0.25, -0.04), and faster decline annually in semantic memory (-0.04, 95% CI: -0.07, -0.01; -0.10, 95% CI: -0.15, -0.05) for Black and Latino participants. Depressive symptoms were associated with lower baseline but not decline in executive function. DISCUSSION: Depressive symptoms were associated with worse cognitive outcomes, with some evidence of heterogeneity across racial/ethnic groups. HIGHLIGHTS: We examined whether baseline depressive symptoms were differentially associated with domain-specific cognition or cognitive decline by race/ethnicity. Depressive symptoms were associated with worse cognitive scores for all racial/ethnic groups across different domains examined. Higher depressive symptoms were associated with faster cognitive decline for semantic memory for Black and Latino participants. The results suggest a particularly harmful association between depressive symptoms and cognition in certain racial/ethnic groups.

Comparison of approaches to control for intracranial volume in research on the association of brain volumes with cognitive outcomes.

Most neuroimaging studies linking regional brain volumes with cognition correct for total intracranial volume (ICV), but methods used for this correction differ across studies. It is unknown whether different ICV correction methods yield consistent results. Using a brain-wide association approach in the MRI substudy of UK Biobank (N = 41,964; mean age = 64.5 years), we used regression models to estimate the associations of 58 regional brain volumetric measures with eight cognitive outcomes, comparing no correction and four ICV correction approaches. Approaches evaluated included: no correction; dividing regional volumes by ICV (proportional approach); including ICV as a covariate in the regression (adjustment approach); and regressing the regional volumes against ICV in different normative samples and using calculated residuals to determine associations (residual approach). We used Spearman-rank correlations and two consistency measures to quantify the extent to which associations were inconsistent across ICV correction approaches for each possible brain region and cognitive outcome pair across 2320 regression models. When the association between brain volume and cognitive performance was close to null, all approaches produced similar estimates close to the null. When associations between a regional volume and cognitive test were not null, the adjustment and residual approaches typically produced similar estimates, but these estimates were inconsistent with results from the crude and proportional approaches. For example, when using the crude approach, an increase of 0.114 (95% confidence interval [CI]: 0.103-0.125) in fluid intelligence was associated with each unit increase in hippocampal volume. However, when using the adjustment approach, the increase was 0.055 (95% CI: 0.043-0.068), while the proportional approach showed a decrease of -0.025 (95% CI: -0.035 to -0.014). Different commonly used methods to correct for ICV yielded inconsistent results. The proportional method diverges notably from other methods and results were sometimes biologically implausible. A simple regression adjustment for ICV produced biologically plausible associations.

Associations of Everyday and Lifetime Experiences of Discrimination With Willingness to Undergo Alzheimer Disease Predictive Testing.

BACKGROUND AND OBJECTIVES: Rapid developments in Alzheimer disease (AD) biomarker research suggest that predictive testing may become widely available. To ensure equal access to AD predictive testing, it is important to understand factors that affect testing interest. Discrimination may influence attitudes toward AD testing, particularly among racially and ethnically minoritized populations, because of structural racism in health care systems. This study examined whether everyday or lifetime discrimination experiences shape interest in AD predictive testing. METHODS: In the 2010 and 2012 biennial Health and Retirement Study waves, respondents were randomly selected to complete questions on interest in receiving free testing that could determine whether they would develop AD in the future. The exposures were everyday discrimination (6 items) and lifetime discrimination (7 items); both were transformed into a binary variable. Logistic regression models predicting interest in AD testing were controlled for deciles of propensity scores for each discrimination measure. Odds ratios were re-expressed as risk differences (RDs). RESULTS: Our analytic sample included 1,499 respondents. The mean age was 67 (SD = 10.2) years, 57.4% were women, 65.7% were White, and 80% endorsed interest in AD predictive testing. Most of the participants (54.7%) experienced everyday discrimination in at least one domain; 24.1% experienced major lifetime discrimination in at least one domain. Those interested in predictive testing were younger (66 vs 70 years) and more likely to be Black (20% vs 15%) or Latinx (14% vs 8%) than participants uninterested in testing. The probability of wanting an AD test was not associated with discrimination for Black (RD everyday discrimination = -0.026; 95% CI [-0.081 to 0.029]; RD lifetime discrimination = -0.012; 95% CI [-0.085 to 0.063]) or Latinx (RD everyday discrimination = -0.023, 95% CI [-0.082 to 0.039]; RD lifetime discrimination = -0.011; 95% CI [-0.087 to 0.064]) participants. DISCUSSION: Despite historical and contemporary experiences of discrimination, Black and Latinx individuals express interest in AD testing. However, Black and Latinx individuals remain underrepresented in AD research, including research on AD testing. Interest in personalized information about dementia risk may be a pathway to enhance their inclusion in research and clinical trials.

Perceived Neighborhood Characteristics and Later-Life Pain Outcomes: Evidence From the Health and Retirement Study.

Objectives: This study examines whether perceived neighborhood characteristics relate to pain outcomes among middle-aged and older adults. Methods: Data were from the Health and Retirement Study (2006-2014; n = 18,814). Perceived neighborhood characteristics were physical disorder, social cohesion, safety, and social ties. We fitted adjusted generalized estimating equation models to evaluate prevalence, incidence, and recovery of moderate-to-severe limiting pain 2 years later. Results: The mean age of our sample was 65.3 years; 54.6% were female and 24.2% reported moderate-to-severe limiting pain at baseline. Positive neighborhood characteristics were associated with low prevalence (e.g., prevalence ratio [PR]: .71 for disorder) and reduced incidence (e.g., PR: .63 for disorder) of moderate-to-severe limiting pain. Positive neighborhood characteristics were associated with a high recovery rate from moderate-to-severe limiting pain (e.g., PR = 1.15 for safety), though the 95% CIs for disorder and cohesion crossed the null. Discussion: Neighborhood characteristics may be important determinants in predicting pain in later life.

Association of cancer history with structural brain aging markers of Alzheimer's disease and related dementias risk.

INTRODUCTION: Cancer survivors are less likely than comparably aged individuals without a cancer history to develop Alzheimer's disease and related dementias (ADRD). METHODS: In the UK Biobank, we investigated associations between cancer history and five structural magnetic resonance imaging (MRI) markers for ADRD risk, using linear mixed-effects models to assess differences in mean values and quantile regression to examine whether associations varied across the distribution of MRI markers. RESULTS: Cancer history was associated with smaller mean hippocampal volume (b = -19 mm3 , 95% CI = -36, -1) and lower mean cortical thickness in the Alzheimer's disease signature region (b = -0.004 mm, 95% CI = -0.007, -0.000). Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history. DISCUSSION: Some brain MRI markers associated with ADRD risk were elevated in adults with a history of cancer. The magnitude of the adverse associations varied across quantiles of neuroimaging markers, and the pattern suggests possible harmful associations for individuals already at high ADRD risk. HIGHLIGHTS: We found no evidence of an inverse association between cancer history and ADRD-related neurodegeneration. Cancer history was associated with smaller mean hippocampal volume and lower mean cortical thickness in the Alzheimer's disease signature region. Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history.

Neighborhood Characteristics and Elevated Blood Pressure in Older Adults.

Importance: The local environment remains an understudied contributor to elevated blood pressure among older adults. Untargeted approaches can identify neighborhood conditions interrelated with racial segregation that drive hypertension disparities. Objective: To evaluate independent associations of sociodemographic, economic, and housing neighborhood factors with elevated blood pressure. Design, Setting, and Participants: In this cohort study, the sample included Health and Retirement Study participants who had between 1 and 3 sets of biennial sphygmomanometer readings from 2006 to 2014 or 2008 to 2016. Statistical analyses were conducted from February 5 to November 30, 2021. Exposures: Fifty-one standardized American Community Survey census tract variables (2005-2009). Main Outcomes and Measures: Elevated sphygmomanometer readings over the study period (6-year period prevalence): a value of at least 140 mm Hg for systolic blood pressure and/or at least 90 mm Hg for diastolic blood pressure. Participants were divided 50:50 into training and test data sets. Generalized estimating equations were used to summarize multivariable associations between each neighborhood variable and the period prevalence of elevated blood pressure, adjusting for individual-level covariates. Any neighborhood factor associated (Simes-adjusted for multiple comparisons P ≤ .05) with elevated blood pressure in the training data set was rerun in the test data set to gauge model performance. Lastly, in the full cohort, race- and ethnicity-stratified associations were evaluated for each identified neighborhood factor on the likelihood of elevated blood pressure. Results: Of 12 946 participants, 4565 (35%) had elevated sphygmomanometer readings (median [IQR] age, 68 [63-73] years; 2283 [50%] male; 228 [5%] Hispanic or Latino, 502 [11%] non-Hispanic Black, and 3761 [82%] non-Hispanic White). Between 2006 and 2016, a lower likelihood of elevated blood pressure was observed (relative risk for highest vs lowest tertile, 0.91; 95% CI, 0.86-0.96) among participants residing in a neighborhood with recent (post-1999) in-migration of homeowners. This association was precise among participants with non-Hispanic White and other race and ethnicity (relative risk, 0.91; 95% CI, 0.85-0.97) but not non-Hispanic Black participants (relative risk, 0.97; 95% CI, 0.85-1.11; P = .48 for interaction) or Hispanic or Latino participants (relative risk, 0.84; 95% CI, 0.65-1.09; P = .78 for interaction). Conclusions and Relevance: In this cohort study of older adults, recent relocation of homeowners to a neighborhood was robustly associated with reduced likelihood of elevated blood pressure among White participants but not their racially and ethnically marginalized counterparts. Our findings indicate that gentrification may influence later-life blood pressure control.

Neighborhood factors and survival to old age: The Jackson Heart Study.

Few studies have evaluated environmental factors that predict survival to old age. Our study included 913 African American participants in the Jackson Heart Study (JHS) who resided in the tri-county area of the Jackson, MS metropolitan area and were 65-80 years at baseline. Participants were followed from 2000 through 2019 for the outcome of survival to 85 years old. We evaluated each of the following census tract-level measures of the social/physical environment as exposures: socioeconomic status, cohesion, violence, disorder, healthy food stores, residential land use, and walkability. We assessed mediation by physical activity and chronic conditions. As a complementary ecologic analysis, we used census-tract data to examine factors associated with a greater life expectancy. A total of 501 (55%) JHS participants survived to age 85 years or older. Higher social cohesion and greater residential land use were modestly associated with survival to old age (risk difference = 25%, 95% CI: 0-49%; and 4%, 95% CI: 1-7%, respectively). These neighborhood effects were modestly mediated through leisure time physical activity; additionally, social cohesion was mediated through home and yard activity. In our ecologic analysis, a greater percentage of homeowners and a greater proportion of people living in partnered families were associated with higher census-tract level life expectancy. African American older adults living in residential neighborhoods or neighborhoods with high social cohesion were more likely to survive to old age.

Projected Impact of Nonpharmacologic Management of Stage 1 Hypertension Among Lower-Risk US Adults.

Background: The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines newly classified 31 million US adults as having stage 1 hypertension. The ACC/AHA guidelines recommend behavioral change without pharmacology for the low-risk portion of this group. However, the nationwide reduction in cardiovascular disease (CVD) and associated healthcare expenditures achievable by evidence-based dietary improvements, sustained weight loss, adequate physical activity, and alcohol moderation remain unquantified. We estimated the effect of systolic BP (SBP) control and behavioral changes on 10-year CVD outcomes and costs. Methods: We used the CVD Policy Model to simulate CVD events, mortality, and healthcare costs among US adults aged 35-64. We simulated interventions on a target population, identified from the 2015-2018 National Health and Nutrition Examination Survey, with low-risk stage 1 systolic hypertension: defined as untreated SBP 130-139 mmHg and diastolic BP <90 mmHg; no history of CVD, diabetes, or chronic kidney disease; and low 10-year risk of CVD. We used published meta-analyses and trials to estimate the effects of behavior modification on SBP. We assessed the extent to which intermittent healthcare utilization or partial uptake of nonpharmacologic therapy would decrease CVD events prevented. Results: Controlling SBP to <130 mmHg among the estimated 8.8 million U.S. adults (51% women) in the target population could prevent 26,100 CVD events, avoid 2,900 deaths, and save $1.6 billion in healthcare costs over 10 years. The Dietary Approaches to Stop Hypertension (DASH) diet could prevent 16,000 CVD events among men and 12,000 among women over a decade. Other nonpharmacologic interventions could avert between 3,700 and 19,500 CVD events. However, only 5.5 million (61%) of the target population regularly utilized healthcare where recommended clinician counseling could occur. Conclusions: As only two-thirds of U.S. adults with Stage 1 hypertension regularly receive medical care, substantial benefits to cardiovascular health and associated costs may only stem from policies that promote widespread adoption and sustained adherence of nonpharmacologic therapy. Future work should quantify the population-level costs, benefits, and efficacy of improving the food system and local infrastructure on health behavior change.

Discrimination, Mediating Psychosocial or Economic Factors, and Antihypertensive Treatment: A 4-Way Decomposition Analysis in the Health and Retirement Study.

Untested psychosocial or economic factors mediate associations between perceived discrimination and suboptimal antihypertensive therapy. This study included 2 waves of data from Health and Retirement Study participants with self-reported hypertension (n = 8,557, 75% non-Hispanic White, 15% non-Hispanic Black, and 10% Hispanic/Latino) over 4 years (baselines of 2008 and 2010, United States). Our primary exposures were frequency of experiencing discrimination, in everyday life or across 7 lifetime circumstances. Candidate mediators were self-reported depressive symptoms, subjective social standing, and household wealth. We evaluated with causal mediation methods the interactive and mediating associations between each discrimination measure and reported antihypertensive use at the subsequent wave. In unmediated analyses, everyday (odds ratio (OR) = 0.86, 95% confidence interval (CI): 0.78, 0.95) and lifetime (OR = 0.91, 95% CI: 0.85, 0.98) discrimination were associated with a lower likelihood of antihypertensive use. Discrimination was associated with lower wealth, greater depressive symptoms, and decreased subjective social standing. Estimates for associations due to neither interaction nor mediation resembled unmediated associations for most discrimination-mediator combinations. Lifetime discrimination was indirectly associated with reduced antihypertensive use via depressive symptomatology (OR = 0.99, 95% CI: 0.98, 1.00). In conclusion, the impact of lifetime discrimination on the underuse of antihypertensive therapy appears partially mediated by depressive symptoms.

Intersectional Discrimination and Change in Blood Pressure Control Among Older Adults: The Health and Retirement Study.

BACKGROUND: Associations between multiple forms of discrimination and blood pressure control in older populations remain unestablished. METHODS: Participants were 14 582 noninstitutionalized individuals (59% women) in the Health and Retirement Study aged at least 51 years (76% non-Hispanic White, 15% non-Hispanic Black, 9% Hispanic/Latino). Primary exposures included the mean frequency of discrimination in everyday life, intersectional discrimination (defined as marginalization ascribed to more than one reason), and the sum of discrimination over the life span. We assessed whether discrimination was associated with a change in measured hypertension status (N = 14 582) and concurrent medication use among reported hypertensives (N = 9 086) over 4 years (2008-2014). RESULTS: There was no association between the frequency of everyday discrimination and change in measured hypertension. Lifetime discrimination was associated with higher odds of hypertension 4 years later among men (odds ratio [OR]: 1.21, 95% confidence interval [CI]: 1.08-1.36) but not women (OR: 0.98, 95% CI: 0.86-1.13). Only among men, everyday discrimination due to at least 2 reasons was associated with a 1.44-fold (95% CI: 1.03-2.01) odds of hypertension than reporting no everyday discrimination, reporting intersectional discrimination was not associated with developing hypertension among women (OR: 0.91, 95% CI: 0.70-1.20). All 3 discriminatory measures were inversely related to time-averaged antihypertensive medication use, without apparent gender differences (eg, OR for everyday discrimination-antihypertensive use associations: 0.85, 95% CI: 0.77-0.94). CONCLUSIONS: Gender differences in marginalization may more acutely elevate hypertensive risk among older men than similarly aged women. Experiences of discrimination appear to decrease the likelihood of antihypertensive medication use among older adults overall.

Recovery From Mobility Limitation in Middle-Aged African Americans: The Jackson Heart Study.

BACKGROUND: Despite evidence that African Americans shoulder a high burden of mobility limitation, little is known about factors associated with recovery. METHOD: Participants from the Jackson Heart Study underwent 3 in-person exams from 2000 to 2013. Mobility limitations were assessed over this period by self-reported limitations in walking half a mile or climbing stairs during annual phone calls. The outcome of interest, recovery from mobility limitation, was defined as no mobility limitation the year following an incident event. Candidate predictor variables were assessed in logistic regression models, including sociodemographic, psychosocial, and health measures. Inverse probability weights were used to address missing data in the outcome. RESULTS: Among 4526 participants (mean [SD] age = 54.5 (12.8) years) without a mobility limitation at baseline, 1445 (32%) had an incident mobility limitation over 12 years of follow-up, and 709 (49%) reported recovery from mobility limitation by 1 year later. Low income and daily discrimination were associated with a lower likelihood of recovery even after adjustment for covariates. In adjusted models, greater comorbidity was associated with a lower likelihood of recovering (p-value for trend = .05). History of heart failure and cancer were associated with a lower likelihood of recovering from mobility limitation (OR: 0.52, 95% CI: 0.29, 0.94 and OR: 0.74, 95% CI: 0.55, 1.00). Adiposity, smoking status, and physical activity were not associated with recovery from mobility limitation. CONCLUSION: Half of incident mobility limitations in this population of middle-aged African Americans were transient. Adverse sociodemographic factors and comorbidities were associated with lower likelihood of recovery.

Perceived Discrimination and Trajectories of C-Reactive Protein: The Jackson Heart Study.

INTRODUCTION: Perceiving discriminatory treatment may contribute to systemic inflammation, a risk factor of cardiovascular pathophysiology. This study evaluated the association of self-reported discrimination with changes in high-sensitivity C-reactive protein and the mediating role of adiposity. METHODS: The sample included 5,145 African-Americans, aged 21-92 years, in the Jackson Heart Study. Everyday, lifetime, and burden from perceived discrimination comprised primary predictors in 3 sets of multivariable linear regression models of baseline (2000-2004) discrimination and natural logarithm of high-sensitivity C-reactive protein. Multivariable linear mixed models assessed mean changes in natural logarithm of high-sensitivity C-reactive protein over the study period (2000-2013). Mediation was quantified by percentage changes in estimates adjusted for BMI, waist circumference, and waist-to-height ratio. Multiple imputation addressed missingness in baseline covariates and in high-sensitivity C-reactive protein taken at all 3 study examinations. Analyses were conducted in 2018. RESULTS: In cross-sectional analyses, male participants in the middle and highest tertiles of lifetime discrimination had natural logarithm of high-sensitivity C-reactive protein levels that were 0.13 (95% CI= -0.24, -0.01) and 0.15 (95% CI= -0.27, -0.02) natural logarithm(mg/dL) lower than those in the lowest tertile. In longitudinal analyses, all participants reporting more frequent everyday discrimination had a 0.07 natural logarithm(mg/dL) greater increase in natural logarithm of high-sensitivity C-reactive protein per examination than those reporting none (95% CI=0.01, 0.12). A similar trend emerged for lifetime discrimination and changes in natural logarithm of high-sensitivity C-reactive protein (adjusted mean increase per visit: 0.04 natural logarithm[mg/dL], 95% CI=0.01, 0.08). Adiposity did not mediate the longitudinal associations. CONCLUSIONS: Everyday and lifetime discrimination were associated with significant high-sensitivity C-reactive protein increases over 13 years. The physiologic response to discrimination may lead to systemic inflammation.