ABCA7, a Genetic Risk Factor Associated with Alzheimer’s Disease Risk in African Americans

African American/Black adults are twice as likely to have Alzheimer’s disease (AD) compared to non-Hispanic White adults. Genetics partially contributes to this disparity in AD risk, among other factors, as there are several genetic variants associated with AD that are more prevalent in individuals of African or European ancestry. The phospholipid-transporting ATPase ABCA7 (ABCA7) gene has stronger associations with AD risk in individuals with African ancestry than in individuals with European ancestry. In fact, ABCA7 has been shown to have a stronger effect size than the apolipoprotein E (APOE) ɛ4 allele in African American/Black adults. ABCA7 is a transmembrane protein involved in lipid homeostasis and phagocytosis. ABCA7 dysfunction is associated with increased amyloid-beta production, reduced amyloid-beta clearance, impaired microglial response to inflammation, and endoplasmic reticulum stress. This review explores the impact of ABCA7 mutations that increase AD risk in African American/Black adults on ABCA7 structure and function and their contributions to AD pathogenesis. The combination of biochemical/biophysical and ‘omics-based studies of these variants needed to elucidate their downstream impact and molecular contributions to AD pathogenesis is highlighted.

Associations between estimated and measured carotid-femoral pulse wave velocity in older Black and White adults: the atherosclerosis risk in communities (ARIC) study

Introduction: Aortic stiffness offers important insight into vascular aging and cardiovascular disease (CVD) risk. The referent measure of aortic stiffness is carotid-femoral pulse wave velocity (cfPWV). cfPWV can be estimated (ePWV) from age and mean arterial pressure. Few studies have directly compared the association of ePWV to measured cfPWV, particularly in non-White adults. Moreover, whether ePWV and cfPWV correlate similarly with CVD risk remains unexplored. Aim: (1) To estimate the strength of the agreement between ePWV and cfPWV in both Black and White older adults; and (2) to compare the associations of ePWV and cfPWV with CVD risk factors and determine whether these associations were consistent across races. Methods and Results: We evaluated 4478 [75.2 (SD 5.0) years] Black and White older adults in the Atherosclerosis Risk in Communities (ARIC) Study. cfPWV was measured using an automated pulse waveform analyzer. ePWV was derived from an equation based on age and mean arterial pressure. Association and agreement between the two measurements were determined using Pearson’s correlation coefficient (r), standard error of estimate (SEE), and Bland-Altman analysis. Associations between traditional risk factors with ePWV and cfPWV were evaluated using linear mixed regression models. We observed weak correlations between ePWV and cfPWV within White adults (r = 0.36) and Black adults (r = 0.31). The mean bias for Bland-Altman analysis was low at -0.17 m/s (95%CI: -0.25 to -0.09). However, the inspection of the Bland-Altman plots indicated systematic bias (P < 0.001), which was consistent across race strata. The SEE, or typical absolute error, was 2.8 m/s suggesting high variability across measures. In models adjusted for sex, prevalent diabetes, the number of prevalent cardiovascular diseases, and medication count, both cfPWV and ePWV were positively associated with heart rate, triglycerides, and fasting glucose, and negatively associated with body mass index (BMI) and smoking status in White adults (P < 0.05). cfPWV and ePWV were not associated with heart rate, triglycerides, and fasting glucose in Black adults, while both measures were negatively associated with BMI in Black adults. Conclusions: Findings suggest a weak association between ePWV and cfPWV in older White and Black adults from ARIC. There were similar weak associations between CVD risk factors with ePWV and cfPWV in White adults with subtle differences in associations in Black adults. One sentence summary: Estimated pulse wave velocity is weakly associated with measured carotid-femoral pulse wave velocity in older Black and White adults in ARIC.

Historical redlining and cardiovascular health: The Multi-Ethnic Study of Atherosclerosis

We investigated historical redlining, a government-sanctioned discriminatory policy, in relation to cardiovascular health (CVH) and whether associations were modified by present-day neighborhood physical and social environments. Data included 4,779 participants (mean age 62 y; SD = 10) from the baseline sample of the Multi-Ethnic Study of Atherosclerosis (MESA; 2000 to 2002). Ideal CVH was a summary measure of ideal levels of seven CVH risk factors based on established criteria (blood pressure, fasting glucose, cholesterol, body mass index, diet, physical activity, and smoking). We assigned MESA participants’ neighborhoods to one of four grades (A: best, B: still desirable, C: declining, and D: hazardous) using the 1930s federal Home Owners’ Loan Corporation (HOLC) maps, which guided decisions regarding mortgage financing. Two-level hierarchical linear and logistic models, with a random intercept to account for participants nested within neighborhoods (i.e., census tracts) were used to assess associations within racial/ethnic subgroups (non-Hispanic White, non-Hispanic Black, Hispanic, and non-Hispanic Chinese). We found that Black adults who lived in historically redlined areas had a 0.82 (95% CI −1.54, −0.10) lower CVH score compared to those residing in grade A (best) neighborhoods, in a given neighborhood and adjusting for confounders. We also found that as the current neighborhood social environment improved the association between HOLC score and ideal CVH weakened (P < 0.10). There were no associations between HOLC grade and CVH measures or effect modification by current neighborhood conditions for any other racial/ethnic group. Results suggest that historical redlining has an enduring impact on cardiovascular risk among Black adults in the United States.

Annual Review of Gerontology and Geriatrics Symposium: Black Older Adults in the Era of Black Lives Matter

Our renewed urgency and engagement in a national dialogue on issues of systemic racism and racial justice provides a much-needed opportunity to expand the discourses, perspectives, and practices used in the study of aging. This symposium features contributions from the 2021 (Vol 41) Annual Review of Gerontology and Geriatrics focusing on the continued development and maturation of scholarship on the lives of older Black Americans. Building on the scholarship and research contributions of prior generations of eminent African American gerontologists, the volume asks: “What do we know about the lived experience of Black older adults and what is there still to be learned?” The contributing authors continue a tradition of research that examines the life histories and contemporary experiences of older Black adults within their relevant social and personal contexts. Symposium presenters from a range of social science fields (sociology, psychology, social work), explore aspects of physical health, stress, cognition, and social well-being in the context of intersecting social dimensions of marriage, family, gender, and neighborhood.

Perceived Everyday Discrimination and C- Reactive Protein Influence on Cognition of Older Black Adults

Black adults and women are more likely to experience serious cognitive decline in older age than their white and male counterparts. Evidence suggests perceived discrimination is associated with poor cognition in older adults, though the mechanisms remain unclear. Perceived discrimination has been linked to elevated inflammatory markers, such as C-reactive protein (CRP), which increases risk for worse cognitive functioning. Yet, little research has investigated whether CRP is implicated in the association between discrimination and cognition among Black older adults or if this relationship differs by gender. Using 2006-2016 data from Black adults ≥65 years old(N=1343) in the nationally representative Health and Retirement Study, random effects linear regression models (1) tested the association between discrimination and cognitive functioning; (2) explored whether this relationship differed for women and men; and (3) assessed whether elevated CRP mediated the association between discrimination and cognitive functioning. More frequent discrimination was associated with worse cognitive functioning (b= -0.24, SE=0.11, p&lt;0.05), though gender did not moderate this relationship. Elevated CRP was significantly associated with worse cognitive functioning (b= 0.40, SE=0.18, p&lt;0.05). Discrimination remained statistically significant in this model, indicating no mediation by CRP. Of note, inclusion of depressive symptoms and cardiometabolic conditions accounted for the association between both discrimination and CRP with cognitive functioning. These findings demonstrate the need for more within-group research on older Black adults documenting the complex relationship between discrimination, inflammation, and cognitive health. This approach will provide greater understanding of the biopsychosocial mechanisms underlying disparities in cognitive functioning in Black adults.

Childhood Socioeconomic Status and Cognitive Aging: An Intersectional Life Course Perspective

Greater childhood socioeconomic status (cSES) is associated with better later life cognition. Largely absent from this literature is how structural racism potentially influences this relationship. Guided by intersectional life course theory, we examined if the influence of cSES and region of schooling on later life cognitive outcomes differs among non-Hispanic White (NHW) and Black older adults. We used data from the 2010-2016 waves of the Health and Retirement Study for participants ages 65 and older in 2010. Using growth mixture modeling, we estimated the associations between race, cSES (parental education, social, and financial capital), and region of schooling at age 10 (southern versus not) on cognitive performance. Consistent with prior research, there was a main effect of race on cognitive performance levels (but not with decline over time), with lower scores among older Black adults, on average. Among NHWs, higher cSES was protective for later life cognition, especially for NHW participants from the South. Although Black older adults who attended school outside of the South had higher levels of cognitive performance than their counterparts who attended school at age 10 in the South, Black older adults who attended school outside of the South--regardless of cSES--still had lower average scores on cognition at baseline than the most disadvantaged NHW participants. This paper implicates the effects of structural racism on cognitive performance among older Black adults, indicating the need for heightened attention to structural racism within interventions for optimizing brain health and promoting equitable cognitive aging across the life course.