Faculty Bibliography

Objective/UNASSIGNED:The study objective was to examine predictors of sleep disturbance and strain among caregivers of persons living with dementia (PLWD). Methods/UNASSIGNED:This cross-sectional study utilized a sample of community-dwelling older adults and their family caregivers drawn from the 2017 National Health and Aging Trends Study and National Study of Caregiving. Multivariable logistic regression was used to assess the association between caregiver and PLWD characteristics and a composite measure of caregiving strain. High caregiving strain was defined as a total score of ≥ 5 on the 6 caregiving strain items (e.g., emotional difficulty, no time for self). We used multivariable proportional odds models to examine predictors of caregiver sleep-related outcomes (trouble falling back to sleep and interrupted sleep), after adjusting for other caregiver and PLWD factors. Results/UNASSIGNED:Of the 1,142 family caregivers, 65.2% were female, 15% were Black, and 14% were Hispanic. Average age was 60 years old. Female caregivers were more likely to report high level of strain compared to male caregivers (OR: 2.61, 95% CI = 1.56, 4.39). Compared to non-Hispanic Whites, non-Hispanic Black and Hispanic caregivers had reduced odds of reporting greater trouble falling back asleep [OR = 0.55, CI (0.36, 0.82) and OR = 0.56, CI (0.34, 0.91), respectively]. The odds of reporting greater trouble falling back asleep was significantly greater among caregivers with high blood pressure vs. caregivers without high blood pressure [OR = 1.62, CI (1.12, 2.33)]. Conclusion/UNASSIGNED:In this cross-sectional study, caregivers with greater sleep difficulty (trouble falling back asleep) were more likely to report having high blood pressure. We found no racial/ethnic differences in interrupted sleep among caregivers to PLWD. These results suggest that interventions to improve sleep among caregivers to PLWD may decrease poor cardiovascular outcomes in this group.

INTRODUCTION/BACKGROUND:Obstructive sleep apnea (OSA) is associated with Alzheimer's disease (AD) biomarkers in cognitively normal (CN) and mild cognitive impaired (MCI) participants. However, independent and combined effects of OSA, amyloid beta (Aβ) and tau-accumulation on AD time-dependent progression risk is unclear. METHODS:Study participants grouped by biomarker profile, as described by the A/T/N scheme, where "A" refers to aggregated Aβ, "T" aggregated tau, and "N" to neurodegeneration, included 258 CN (OSA-positive [OSA+] [A+TN+ n = 10, A+/TN- n = 6, A-/TN+ n = 10, A-/TN- n = 6 and OSA-negative [OSA-] [A+TN+ n = 84, A+/TN- n = 11, A-/TN+ n = 96, A-/TN- n = 36]) and 785 MCI (OSA+ [A+TN+ n = 35, A+/TN- n = 15, A-/TN+ n = 25, A-/TN- n = 16] and OSA- [A+TN+ n = 388, A+/TN- n = 28, A-/TN+ n = 164, A-/TN- n = 114]) older-adults from the Alzheimer's Disease Neuroimaging Initiative cohort. Cox proportional hazards regression models estimated the relative hazard of progression from CN-to-MCI and MCI-to-AD, among baseline OSA CN and MCI patients, respectively. Multi-level logistic mixed-effects models with random intercept and slope investigated the synergistic associations of self-reported OSA, Aβ, and tau burden with prospective cognitive decline. RESULTS:Independent of TN-status (CN and MCI), OSA+/Aβ+ participants were approximately two to four times more likely to progress to MCI/AD (P < .001) and progressed 6 to 18 months earlier (P < .001), compared to other participants combined (ie, OSA+/Aβ-, OSA-/Aβ+, and OSA-/Aβ-). Notably, OSA+/Aβ- versus OSA-/Aβ- (CN and MCI) and OSA+/TN- versus OSA-/TN- (CN) participants showed no difference in the risk and time-to-MCI/AD progression. Mixed effects models demonstrated OSA synergism with Aβ (CN and MCI [β = 1.13, 95% confidence interval (CI), 0.74 to 1.52, and β = 1.18, 95%CI, 0.82 to 1.54]) respectively, and with tau (MCI [β = 1.31, 95% CI, 0.87 to 1.47]), P < .001 for all. DISCUSSION/CONCLUSIONS:OSA acts in synergism with Aβ and with tau, and all three acting together result in synergistic neurodegenerative mechanisms especially as Aβ and tau accumulation becomes increasingly abnormal, thus leading to shorter progression time to MCI/AD in CN and MCI-OSA patients, respectively.

Here we review the impact of obstructive sleep apnea (OSA) on biomarkers of Alzheimer's disease (AD) pathogenesis, neuroanatomy, cognition and neurophysiology, and present the research investigating the effects of continuous positive airway pressure (CPAP) therapy. OSA is associated with an increase in AD markers amyloid-β and tau measured in cerebrospinal fluid (CSF), by Positron Emission Tomography (PET) and in blood serum. There is some evidence suggesting CPAP therapy normalizes AD biomarkers in CSF but since mechanisms for amyloid-β and tau production/clearance in humans are not completely understood, these findings remain preliminary. Deficits in the cognitive domains of attention, vigilance, memory and executive functioning are observed in OSA patients with the magnitude of impairment appearing stronger in younger people from clinical settings than in older community samples. Cognition improves with varying degrees after CPAP use, with the greatest effect seen for attention in middle age adults with more severe OSA and sleepiness. Paradigms in which encoding and retrieval of information are separated by periods of sleep with or without OSA have been done only rarely, but perhaps offer a better chance to understand cognitive effects of OSA than isolated daytime testing. In cognitively normal individuals, changes in EEG microstructure during sleep, particularly slow oscillations and spindles, are associated with biomarkers of AD, and measures of cognition and memory. Similar changes in EEG activity are reported in AD and OSA, such as "EEG slowing" during wake and REM sleep, and a degradation of NREM EEG microstructure. There is evidence that CPAP therapy partially reverses these changes but large longitudinal studies demonstrating this are lacking. A diagnostic definition of OSA relying solely on the Apnea Hypopnea Index (AHI) does not assist in understanding the high degree of inter-individual variation in daytime impairments related to OSA or response to CPAP therapy. We conclude by discussing conceptual challenges to a clinical trial of OSA treatment for AD prevention, including inclusion criteria for age, OSA severity, and associated symptoms, the need for a potentially long trial, defining relevant primary outcomes, and which treatments to target to optimize treatment adherence.

BACKGROUND:This study examined the relationships between resilience and sleep disturbance in a diverse sample of older women with a history of hypertension and whether this relationship is moderated by individuals' race/ethnicity. METHODS:Sample includes 700 females from a community-based study in Brooklyn, New York with a mean age of 60.7 years (SD=6.52). Of the participants, 28.1% were born in the U.S.; 71% were African-descent, 17.4% were European and 11.6% were Hispanics descents. Data were gathered on demographics and sleep disturbance using the Comprehensive Assessment and Referral Evaluation (CARE) and the Stress Index Scale (SIS). Resilience Factors were assessed with both the Index of Self-Regulation of Emotion (ISE) and religious health beliefs. Chi-Square, Anova, Student t-tests, and multilinear regression analysis were conducted to explore associations between resilience factors and sleep disturbance. Associations between resilience factors and sleep disturbance were examined using stratified multilinear regression analysis in three models by race/ethnicity. Regression models was conducted examining the interaction between resilience factors and stress RESULTS: Resilience factor, ISE emerged as the strongest independent predictor of sleep disturbance [B(SE) = -0.368(0.008); p < .001] for African descents. ISE was not a significant predictor of sleep disturbance among Hispanic participants [B(SE) = -0.218(0.022);p = .052], however interaction effect analysis revealed that stress level moderates significantly the relationship between ISE, and their sleep disturbance [B(SE) = 0.243(0.001);p = .036]. CONCLUSIONS:Results of our study suggest that resilience factors might be a more important protective factor for sleep disturbance among diverse older females.