Faculty Bibliography

Anxiety is highly prevalent in Alzheimer's disease (AD), correlating with cerebrospinal fluid/positron emission tomography biomarkers and disease progression. Relationships to plasma biomarkers are unclear. Herein, we compare levels of plasma biomarkers in research participants with and without anxiety at cognitively normal, mild cognitive impairment, and AD dementia stages. We observed significantly higher plasma tau/amyloid-β₄₂ ratio in AD participants with anxiety versus those without, but did not observe differences at other stages or plasma biomarkers. No such relationships were evident with depression. These results support a unique pathophysiological relationship between anxiety and AD that can be reflected in plasma biomarkers, suggestive of heightened neurodegeneration.

Despite efforts in recent years, including in policy and research, to address health disparities in the United States, many of those disparities continue to fester in marginalized racial/ethnic populations. Understanding sleep health disparities is critical in understanding the health and wellness of these groups. Using obstructive sleep apnea (OSA) in Black populations as a focus, this paper presents the role of race and ethnicity in the clinical understanding of sleep health-related issues by medical practitioners and the implications of the lack of clear policies or best practices to guide medical practitioners' attempts to meet sleep-related needs of marginalized racial/ethnic populations. Furthermore, the knowledge gap may be further complicated by the poor understanding and integration of existing evidence with the many, complex, sleep-associated co-morbidities. Policymaking in this area ought to be based on the ethical implications of disparate sleep-related health outcomes by race and ethnicity. So, we conclude by offering recommendations for developing ethically sound policies for addressing sleep problems in marginalized racial and ethnic populations.

BACKGROUND:Subjective cognitive decline (SCD), considered a preclinical dementia stage, is less understood in Hispanics, a high-risk group for dementia. We investigated SCD to mild cognitive impairment (MCI) progression risk, as well as baseline and longitudinal features of depressive symptoms, SCD complaints, and objective cognitive performance among Hispanics compared to non-Hispanic Whites (NHW). METHODS:Hispanic (n = 23) and NHW (n = 165) SCD participants were evaluated at baseline and 2-year follow-up. Evaluations assessed function, depressive symptoms, SCD, and objective cognitive performance. RESULTS:Hispanic ethnicity associated with a significantly increased risk of 2-year progression of SCD to MCI compared to NHW. This increased risk associated with increased depressive symptoms, distinctive SCD features, and elevated amnestic and non-amnestic objective cognitive decline. This supports further research to refine the assessment of preclinical dementia in this high-risk group.

Anxiety is highly prevalent in Alzheimer's disease (AD), correlating with CSF/PET biomarkers and disease progression. Relationships to plasma biomarkers are unclear. Herein, we compare levels of plasma biomarkers in research participants with and without anxiety at cognitively normal, mild cognitive impairment, and AD dementia stages. We observed significantly higher plasma tau/Aβ42 ratio in AD participants with anxiety versus those without, but did not observe differences at other stages or plasma biomarkers. No such relationships were evident with depression. These results support a unique pathophysiological relationship between anxiety and AD that can be reflected in plasma biomarkers, suggestive of heightened neurodegeneration.

BACKGROUND:We examined drivers of self and study partner reports of memory loss in mild cognitive impairment (MCI) from Alzheimer (AD-MCI) and vascular disease (Va-MCI). METHODS:We performed retrospective cross-sectional analyses of participants with AD-MCI (n=2874) and Va-MCI (n=376) from the National Alzheimer's Coordinating Center data set. Statistical analysis utilized 2-sided t test or the Fisher exact test. RESULTS:Compared with AD-MCI, Va-MCI subjects (24.5% vs. 19.7%, P=0.031) and study partners (31.4% vs. 21.6%, P<0.0001) were more likely to deny memory loss. Black/African Americans were disproportionately represented in the group denying memory loss in AD-MCI (20.0% vs. 13.2%, P<0.0001) and Va-MCI (33.7% vs. 18.0%, P=0.0022). Study partners of participants with these features also disproportionately denied memory loss: female (AD-MCI: 60.1% vs. 51.7%, P=0.0002; Va-MCI: 70.3% vs. 52.3%, P=0.0011), Black/African American (AD-MCI: 23.5% vs. 11.98%, P<0.0001; Va-MCI: 48.8% vs. 26.5%, P=0.0002), and <16 years of education (AD-MCI only: 33.9% vs. 16.3%, P=0.0262). In AD-MCI and Va-MCI, participants with anxiety were disproportionately represented in the group endorsing memory loss (AD: 28.2% vs. 17.4%, P<0.0001; Va: 31.5% vs. 16.1%, P=0.0071), with analogous results with depression. CONCLUSION/CONCLUSIONS:The findings would suggest extra vigilance in interview-based MCI detection of persons at-risk for self-based or informant-based misreport.

Background: Past research suggests that subjective cognitive decline serves as an early and potentially important indicator that individuals may be at risk for future cognitive decline or neurodegenerative conditions. However, there is a dearth of studies on factors influencing the experience of subjective cognitive decline in Black Americans, especially in Black American men. Objective: The current study explored correlates of subjective cognitive decline in Black American men. Participants: A total of 117 Black American men, with a mean age of 38.5 (SD = 7.14) years, participated in the study. Measurement: Participants completed a survey that assessed their demographic characteristics, self-rated health, neighborhood problems, length of residency in neighborhood, bodily symptoms, sleep comorbidities, sleep difficulties, and subjective cognitive decline. Linear regression analyses was performed and standardized beta coefficients were reported to describe the estimated independent effect of the predictor variables. Results: We found that socioecomic status (β = −.222, p=.003), bodily symptoms (β =.246, p=.005), length of residency in neighborhood (β =.157, p=.029), and sleep difficulties (β =.305, p<.001) were significant correlates of subjective cognitive decline among Black American men. Conclusion: These findings underscore the intricate roles of socioeconomic status, bodily symptoms, neighborhood factors, and sleep health in shaping subjective cognitive experiences in this population. Research on subjective cognitive decline can contribute to the early identification of individuals at risk for cognitive decline, allowing for timely interventions, lifestyle modifications, and potential preventive measures.

OBJECTIVES:Subjective cognitive decline (SCD) is a preclinical stage of AD. White matter hyperintensities (WMH), an MRI marker of cerebral small vessel disease, associate with AD biomarkers and progression. The impact of WMH on SCD phenotype is unclear. METHODS/DESIGN:A retrospective, cross-sectional analysis was conducted on a diverse cohort with SCD evaluated at the NYU Alzheimer's Disease Research Center between January 2017 and November 2021 (n = 234). The cohort was dichotomized into none-to-mild (n = 202) and moderate-to-severe (n = 32) WMH. Differences in SCD and neurocognitive assessments were evaluated via Wilcoxon or Fisher exact tests, with p-values adjusted for demographics using multivariable logistic regression. RESULTS:Moderate-to-severe WMH participants reported more difficulty with decision making on the Cognitive Change Index (1.5 SD 0.7 vs. 1.2 SD 0.5, p = 0.0187) and worse short-term memory (2.2 SD 0.4 vs. 1.9 SD 0.3, p = 0.0049) and higher SCD burden (9.5 SD 1.6 vs. 8.7 SD 1.7, p = 0.0411) on the Brief Cognitive Rating Scale. Moderate-to-severe WMH participants scored lower on the Mini-Mental State Examination (28.0 SD 1.6 vs. 28.5 SD 1.9, p = 0.0491), and on delayed paragraph (7.2 SD 2.0 vs. 8.8 SD 2.9, p = 0.0222) and designs recall (4.5 SD 2.3 vs. 6.1 SD 2.5, p = 0.0373) of the Guild Memory Test. CONCLUSIONS:In SCD, WMH impact overall symptom severity, specifically in executive and memory domains, as well as objective performance on global and domain-specific tests in verbal memory and visual working/associative memory.

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.

There is an urgent need for an in-depth and systematic assessment of a wide range of predictive factors related to populations most at risk for delaying and refusing COVID-19 vaccination as cases of the disease surge across the United States. Many studies have assessed a limited number of general sociodemographic and health-related factors related to low vaccination rates. Machine learning methods were used to assess the association of 151 social and health-related risk factors derived from the American Community Survey 2019 and the Centers for Disease Control and Prevention (CDC) BRFSS with the response variables of vaccination rates and unvaccinated counts in 1,555 ZIP Codes in California. The performance of various analytical models was evaluated according to their ability to regress between predictive variables and vaccination levels. Machine learning modeling identified the Gradient Boosting Regressor (GBR) as the predictive model with a higher percentage of the explained variance than the variance identified through linear and generalized regression models. A set of 20 variables explained 72.90% of the variability of unvaccinated counts among ZIP Codes in California. ZIP Codes were shown to be a more meaningful geo-local unit of analysis than county-level assessments. Modeling vaccination rates was not as effective as modeling unvaccinated counts. The public health utility of this model provides for the analysis of state and local conditions related to COVID-19 vaccination use and future public health problems and pandemics.