Our analyses aimed to assess health status and critical needs of caregivers of persons with dementia (PWD) during the COVID-19 pandemic by gender. Between March 2021 and August 2021, respondents (n = ...267) were recruited from an Alzheimer's disease (AD) listserv at an US academic center to complete a questionnaire to capture sociodemographic data, caregiving characteristics, health status, status of COVID-19 testing, and COVID-19 preventative practices during the pandemic. Women caregivers reported needing assistance with caregiving responsibilities, whereas men caregivers needed assistance with health and social resources. More men caregivers also reported psychological distress compared to women caregivers. Our findings indicated significant differences in the resources needed and psychological distress of women and men who cared for PWD during the COVID-19 pandemic. The development of recommendations and resources with both men and women caregivers in mind may be beneficial to support informal caregivers during emergency situations.
The ATP-binding cassette, subfamily A (ABC1), member 7 (ABCA7) gene is associated with Alzheimer’s disease (AD) risk in populations of African, Asian, and European ancestry1-5. Numerous ABCA7 ...mutations contributing to risk have been identified, including a 44 base pair deletion (rs142076058) specific to individuals of African ancestry and predicted to cause a frameshift mutation (p.Arg578Alafs) (Cukier et al., 2016). The UMi043-A human induced pluripotent stem cell line was derived from an African American individual with AD who is heterozygous for this deletion and is a resource to further investigate ABCA7 and how this African-specific deletion may influence disease pathology.
The objective of this study was to investigate attitudes toward brain donation and perceptions of medical research that influence brain donation among African Americans. Cross-sectional surveys were ...administered to African American community members (n = 227). Findings indicate that only 27% of respondents were willing to donate their brain. As medical mistrust was not found to be a significant barrier to research participation, there may be opportunity to increase brain donation by providing information about Alzheimer's disease and brain donation to potential donors and their families so that informed decisions about participating in research can be made.
African Americans continue to have worse health outcomes despite attempts to reduce health disparities. This is due, in part, to inadequate access to healthcare, but also to the health care and ...medical mistrust experienced by communities of color. Churches and worship centers have historically served as cultural centers of trusted resources for educational, financial, and health information within African American communities and a growing number of collaborations have developed between academic institutions and community/faith entities. Herein, we describe the infrastructure of a true and sustainable partnership developed with > 100 prominent faith leaders within the Piedmont Triad region of North Carolina for the purpose of developing or expanding existing health ministries within houses of worship, to improve health literacy and overall health long-term. The Triad Pastors Network is an asset-based partnership between the Maya Angelou Center for Health Equity at Wake Forest University School of Medicine and faith leaders in the Piedmont Triad region of North Carolina that was created under the guiding principles of community engagement to improve health equity and decrease health disparities experienced by African American communities. A partnership in which co-equality and shared governance are the core of the framework provides an effective means of achieving health-related goals in a productive and efficient manner. Faith-based partnerships are reliable approaches for improving the health literacy needed to address health disparities and inequities in communities of color.
There is a paucity of genetic studies of Alzheimer Disease (AD) in individuals of African Ancestry, despite evidence suggesting increased risk of AD in the African American (AA) population. We ...performed whole-genome sequencing (WGS) and multipoint linkage analyses in 51 multi-generational AA AD families ascertained through the Research in African American Alzheimer Disease Initiative (REAAADI) and the National Institute on Aging Late Onset Alzheimer's disease (NIA-LOAD) Family Based Study. Variants were prioritized on minor allele frequency (<0.01), functional potential of coding and noncoding variants, co-segregation with AD and presence in multi-ancestry ADSP release 3 WGS data. We identified a significant linkage signal on chromosome 5q35 (HLOD=3.3) driven by nine families. Haplotype segregation analysis in the family with highest LOD score identified a 3'UTR variant in INSYN2B with the most functional evidence. Four other linked AA families harbor within-family shared variants located in INSYN2B's promoter or enhancer regions. This AA family-based finding shows the importance of diversifying population-level genetic data to better understand the genetic determinants of AD on a global scale.
INTRODUCTION
The underrepresentation of African Americans (AAs) in Alzheimer's disease (AD) research may limit potential benefits from translational applications. This article describes an approach ...to recruit AA families into an AD genomic study and characteristics of seeds (family connectors) used to overcome recruitment barriers of AA families into AD research.
METHODS
A four‐step outreach and snowball sampling approach relying on family connectors was used to recruit AA families. Descriptive statistics of a profile survey were gathered to understand the demographic and health characteristics of family connectors.
RESULTS
Twenty‐five AA families (117 participants) were enrolled in the study via family connectors. Most family connectors self‐identified as female (88%), were 60 years of age or older (76%), and attained post‐secondary education (77%).
DISCUSSION
Community‐engaged strategies were essential to recruit AA families. Relationships between study coordinators and family connectors build trust early in the research process among AA families.
Highlights
Community events were most effective for recruiting African American families.
Family connectors were primarily female, in good health, and highly educated.
Systematic efforts by researchers are necessary to “sell” a study to participants.
Abstract
Most Alzheimer’s disease (AD)-associated genetic variants do not change protein coding sequence and thus likely exert their effects through regulatory mechanisms. RNA editing, the ...post-transcriptional modification of RNA bases, is a regulatory feature that is altered in AD patients that differs across ancestral backgrounds. Editing QTLs (edQTLs) are DNA variants that influence the level of RNA editing at a specific site. To study the relationship of DNA variants genome-wide, and particularly in AD-associated loci, with RNA editing, we performed edQTL analyses in self-reported individuals of African American (AF) or White (EU) race with corresponding global genetic ancestry averaging 82.2% African ancestry (AF) and 96.8% European global ancestry (EU) in the two groups, respectively. We used whole-genome genotyping array and RNA sequencing data from peripheral blood of 216 AD cases and 212 age-matched, cognitively intact controls. We identified 2144 edQTLs in AF and 3579 in EU, of which 1236 were found in both groups. Among these, edQTLs in linkage disequilibrium (r2 > 0.5) with AD-associated genetic variants in the SORL1, SPI1 and HLA-DRB1 loci were associated with sites that were differentially edited between AD cases and controls. While there is some shared RNA editing regulatory architecture, most edQTLs had distinct effects on the rate of RNA editing in different ancestral populations suggesting a complex architecture of RNA editing regulation. Altered RNA editing may be one possible mechanism for the functional effect of AD-associated variants and may contribute to observed differences in the genetic etiology of AD between ancestries.
Cognitive and functional abilities in individuals with Alzheimer's disease (AD) pathology (ADP) are highly variable. Factors contributing to this variability are not well understood. Previous ...research indicates that higher educational attainment (EA) correlates with reduced cognitive impairments among those with ADP. While cognitive and functional impairments are correlated, they are distinguishable in their manifestations.
To investigate whether levels of education are associated with functional impairments among those with ADP.
This research involved 410 African American (AA) individuals (Institutional Review Boards 20070307, 01/27/2023) to ascertain whether EA correlates with functional resilience and if this effect varies between APOE ɛ4 carriers and non-carriers. Utilizing EA as a cognitive reserve proxy, CDR-FUNC as a functional difficulties measure, and blood pTau181 as an ADP proxy, the non-parametric Mann-Whitney U test assessed the relationship between EA and CDR-FUNC in individuals with advanced pTau181 levels.
The results showed that EA correlated with functional difficulties in AA individuals with high levels of pTau181, such that individuals with high EA are more likely to have better functional ability compared to those with lower EA (W = 730.5, p = 0.0007). Additionally, we found that the effect of high EA on functional resilience was stronger in ɛ4 non-carriers compared to ɛ4 carriers (W = 555.5, p = 0.022).
This study extends the role of cognitive reserve and EA to functional performance showing that cognitive reserve influences the association between ADP burden and functional difficulties. Interestingly, this protective effect seems less pronounced in carriers of the strong genetic risk allele ɛ4.
Background
Alzheimer disease (AD) is more prevalent in African American (AA) and Hispanic White (HIW) compared to Non‐Hispanic White (NHW) individuals. Similarly, neuropsychiatric symptoms (NPS) vary ...by population in AD. This is likely the result of both sociocultural and genetic ancestral differences. However, the impact of these NPS on AD in different groups is not well understood.
Methods
Self‐declared AA, HIW, and NHW individuals were ascertained as part of ongoing AD genetics studies. Participants who scored higher than 0.5 on the Clinical Dementia Rating (CDR) Scale (CDR) were included. Group similarities and differences on Neuropsychiatric Inventory Questionnaire (NPI‐Q) outcomes (NPI‐Q total score, NPI‐Q items) were evaluated using univariate ANOVAs and post hoc comparisons after controlling for sex and CDR stage.
Results
Our sample consisted of 498 participants (26% AA; 30% HIW; 44% NHW). Overall, NPI‐Q total scores differed significantly between our groups, with HIW having the highest NPI‐Q total scores, and by AD stage as measured by CDR. We found no significant difference in NPI‐Q total score by sex. There were six NPI‐Q items with comparable prevalence in all groups and six items that significantly differed between the groups (Anxiety, Apathy, Depression, Disinhibition, Elation, and Irritability). Further, within the HIW group, differences were found between Puerto Rican and Cuban American Hispanics across several NPI‐Q items. Finally, Six NPI‐Q items were more prevalent in the later stages of AD including Agitation, Appetite, Hallucinations, Irritability, Motor Disturbance, and Nighttime Behavior.
Conclusions
We identified differences in NPS among HIW, AA, and NHW individuals. Most striking was the high burden of NPS in HIW, particularly for mood and anxiety symptoms. We suggest that NPS differences may represent the impact of sociocultural influences on symptom presentation as well as potential genetic factors rooted in ancestral background. Given the complex relationship between AD and NPS it is crucial to discern the presence of NPS to ensure appropriate interventions.
Key points
Our study sought to determine if there are differences in neuropsychiatric symptom prevalence, as measured by the Neuropsychiatric Inventory Questionnaire (NPI‐Q), among self‐declared African American (AA), Hispanic, and Non‐Hispanic White (NHW) individuals with Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI).
While the prevalence of several NPI‐Q symptoms was consistent across the three groups our Hispanic participants showed a greater overall burden of neuropsychiatric symptoms—especially anxiety and mood symptoms (i.e., Anxiety, Depression, Apathy, and Irritability items). By contrast, African Americans reported significantly more behavioral problems as reflected on the Disinhibition and Elation items.
The variability in the prevalence of neuropsychiatric symptoms among different populations (e.g., mood and anxiety symptoms in HIW) represents both underlying genetic factors rooted in ancestral background as well as sociocultural influences on the measurement and reporting of NPS.
Little is known about the post-transcriptional mechanisms that modulate the genetic effects in the molecular pathways underlying Alzheimer disease (AD), and even less is known about how these changes ...might differ across diverse populations. RNA editing, the process that alters individual bases of RNA, may contribute to AD pathogenesis due to its roles in neuronal development and immune regulation. Here, we pursued one of the first transcriptome-wide RNA editing studies in AD by examining RNA sequencing data from individuals of both African-American (AA) and non-Hispanic White (NHW) ethnicities. Whole transcriptome RNA sequencing and RNA editing analysis were performed on peripheral blood specimens from 216 AD cases (105 AA, 111 NHW) and 212 gender matched controls (105 AA, 107 NHW). 449 positions in 254 genes and 723 positions in 371 genes were differentially edited in AA and NHW, respectively. While most differentially edited sites localized to different genes in AA and NHW populations, these events converged on the same pathways across both ethnicities, especially endocytic and inflammatory response pathways. Furthermore, these differentially edited sites were preferentially predicted to disrupt miRNA binding and induce nonsynonymous coding changes in genes previously associated with AD in molecular studies, including PAFAH1B2 and HNRNPA1. These findings suggest RNA editing is an important post-transcriptional regulatory program in AD pathogenesis.
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