Faculty Bibliography

Impairments of the sleep architecture due to disrupted sleep in individuals with obstructive sleep apnea (OSA) may result in reduced slow wave sleep (SWS), intermittent hypoxemia, and excessive day time sleepiness- all factors that have been shown to impact Alzheimer's disease (AD) risk. In this commentary, we comment on the work by Cavuoto and colleagues in which they examine the associations between nocturnal hypoxemia or sleep disruptions (during SWS) and amyloid-β burden in individuals with OSA. We review the findings in the context of other similar studies and highlight the strengths and weaknesses of these published studies. We note the importance of examining these relationships longitudinally with a large sample size, including considering sleep health disparities, vascular components, and multiple cognitive domain tests.

INTRODUCTION/BACKGROUND:The projected growth of Alzheimer's disease (AD) and AD-related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry into structural and social determinants of health (S/SDOH) as fundamental drivers of disparities in AD/ADRD. METHODS:In this review, we employ Bronfenbrenner's ecological systems theory as a framework to posit how S/SDOH impact AD/ADRD risk and outcomes. RESULTS:Bronfenbrenner defined the "macrosystem" as the realm of power (structural) systems that drive S/SDOH and that are the root cause of health disparities. These root causes have been discussed little to date in relation to AD/ADRD, and thus, macrosystem influences, such as racism, classism, sexism, and homophobia, are the emphasis in this paper. DISCUSSION/CONCLUSIONS:Under Bronfenbrenner's macrosystem framework, we highlight key quantitative and qualitative studies linking S/SDOH with AD/ADRD, identify scientific gaps in the literature, and propose guidance for future research. HIGHLIGHTS/CONCLUSIONS:Ecological systems theory links structural/social determinants to AD/ADRD. Structural/social determinants accrue and interact over the life course to impact AD/ADRD. Macrosystem is made up of societal norms, beliefs, values, and practices (e.g., laws). Most macro-level determinants have been understudied in the AD/ADRD literature.

Objective: We determined the interactive associations of apolipoprotein e4 (APOE-e4), and obstructive sleep apnea (OSA) on biomarkers of Alzheimer's disease and examined for racial/ethnic differences of this association. Methods: We used data from the National Alzheimer's Coordinating Center Uniform Dataset (NACC UDS). All participants undergo annual observations, including demographic survey, battery of neuropsychological tests, blood draw (with genotyping), and a clinical evaluation with medical and cognitive/dementia status assessment, while a subset of participants have cerebrospinal fluid (CSF) biomarkers and neuroimaging data. Biomarkers of AD were characterized as the presence of abnormally low amyloid in CSF, via validated Aβ42 cut off protocols, and total segmented hippocampal volume, and volume of white matter hyper intensities (WMH). While clinical markers (to preview cognitive relationships) were characterized via the Montreal Cognitive Assessment (MOCA). Results: Biomarker and clinical marker data were derived from 1,387 participants at baseline (mean age = 69.73 � 8.32; 58.6% female; 13.7% Black/African American), 18.4% of the sample had sleep apnea, and 37.9% were APOE-e4 carriers. Our results confirmed previous reports that OSA and APOE-e4 were independently associated with AD through abnormal levels of amyloid (F(1,306) = 4.27; p = 0.040; F(1,285) = 60.88; p < 0.000, respectively), WMH volume (F(1,306) = 4.27; p = 0.040; F(1,285) = 60.88; p < 0.000, respectively), and MOCA scores (F(1,306) = 4.27; p = 0.040; F(1,285) = 60.88; p < 0.000, respectively). No significant interaction between OSA and APOE-e4 relative to amyloid emerged, however, race stratified analyses indicated the interaction of OSA and APOE-e4 and was significantly associated with WMH and hippocampal volume in Black/African American, but not white participants. Conclusion: OSA and APOE-e4 are interactively associated with WHM in Black/African Americans. This interaction may partially explicate increased levels of risk in this population.

BACKGROUND:Down syndrome (DS) population has a very high prevalence of obstructive sleep apnoea (OSA), but this remains underdiagnosed. Hence, we aimed to evaluate caregiver's knowledge of OSA and related sociodemographic factors that could contribute to OSA screening patterns in this population. METHODS:An online survey though the LuMind IDSC Foundation focused on OSA diagnosis, treatments and the number of sleep studies performed. Data were compared between subjects born before and after the American Academy of Pediatrics (AAP) recommendations for OSA screening. RESULTS:Of the caregivers, 724 (parents 96.3%), responded to the survey. The median [interquartile (IQR)] age of the subjects with DS was 12 [20;7] years. The majority (84.3%) had sleep apnoea diagnosis, and half of them were initially referred for a sleep study due to disturbed sleep symptoms. Only 58.7% of the responders were aware of the AAP recommendations. This was linked to higher socioeconomic and/or educational level and to an earlier OSA diagnosis. The median (IQR) age of OSA diagnosis was lowered after the AAP guidelines publication compared with before its publication (3 [4;2] years vs. 10 [18;5] years, P < 0.000). Adenotonsillectomy (81.9%) and continuous positive airway pressure (61.5%) were the most commonly prescribed treatments. Few had discussed other new therapies such as hypoglossal nerve stimulation (16.0%). Only 16.0% of the subjects repeated the sleep study to monitor OSA with ageing, and 30.2% had to wait more than 4 years between studies. CONCLUSIONS:This study reinforces the need to improve OSA knowledge of caregivers and clinicians of individuals with DS to promote an earlier diagnosis and optimal treatment of OSA in this population.

Sex or gender differences in the risk of Alzheimer's disease and related dementias (ADRD) differ by world region, suggesting that there are potentially modifiable risk factors for intervention. However, few epidemiological or clinical ADRD studies examine sex differences; even fewer evaluate gender in the context of ADRD risk. The goals of this perspective are to: (1) provide definitions of gender, biologic sex, and sexual orientation. and the limitations of examining these as binary variables; (2) provide an overview of what is known with regard to sex and gender differences in the risk, prevention, and diagnosis of ADRD; and (3) discuss these sex and gender differences from a global, worldwide perspective. Identifying drivers of sex and gender differences in ADRD throughout the world is a first step in developing interventions unique to each geographical and sociocultural area to reduce these inequities and to ultimately reduce global ADRD risk. HIGHLIGHTS: The burden of dementia is unevenly distributed geographically and by sex and gender. Scientific advances in genetics and biomarkers challenge beliefs that sex is binary. Discrimination against women and sex and gender minority (SGM) populations contributes to cognitive decline. Sociocultural factors lead to gender inequities in Alzheimer's disease and related dementias (ADRD) worldwide.

OBJECTIVES/OBJECTIVE:Discrimination is a major contributor to health disparities between Black and White older adults. Although the health effects of discrimination are well established, less is known about factors that may intervene in the discrimination-health connection, such as coping strategies. The study aim was to determine whether John Henryism (JH; high-effort coping) moderates the association between racial discrimination and hypertension in nationally representative samples of older African Americans and Caribbean Blacks. METHODS:The analytic sample was drawn from the National Survey of American Life-Reinterview, which was conducted 2001-2003, and included African Americans (N = 546) and Caribbean Blacks (N = 141) aged 55 and older. Study variables included racial discrimination, JH, and hypertension. Logistic regressions, which controlled key sociodemographic differences, were used to test the study aim. RESULTS:Among both Black ethnic groups, discrimination and JH were not associated with hypertension. For African Americans low and moderate in JH, discrimination was unrelated to hypertension; discrimination was positively associated with hypertension for African Americans high in JH. For Caribbean Blacks, discrimination was positively associated with hypertension among respondents low in JH. Among Caribbean Blacks moderate and high in JH, discrimination was not associated with hypertension. DISCUSSION/CONCLUSIONS:The findings indicate that JH, in the face of discrimination, is associated with hypertension of older African Americans but may be an effective coping strategy for older Caribbean Blacks due to cultural and sociodemographic differences between the 2 ethnic groups. Future research should investigate the differing mechanisms by which JH influences health in heterogeneous older Black populations.