Faculty Bibliography

BACKGROUND AND OBJECTIVES/UNASSIGNED:The effect of the ambient environment, sound, light, and movement, on the nighttime rest-activity of patients hospitalized with moderate-severe traumatic brain injury (TBI) is poorly understood. The purpose of this study was to examine how sound, light, and movement in these patients' hospital rooms may contribute to nighttime awakenings. METHODS/UNASSIGNED:An observational design was used with 18 adult participants on a neuroscience step-down unit diagnosed with moderate-severe TBI. For up to five consecutive nights, actigraphy was used to capture nighttime awakenings while a custom-made multisensory device captured sound, light, and movement exposures in the participant's room. RESULTS/UNASSIGNED:< .05), but reductions in light did not. CONCLUSION/UNASSIGNED:The ambient environment seems to impede restful sleep in immediate post-injury phase of patients with moderate-severe TBI.

STUDY OBJECTIVES/OBJECTIVE:Obstructive sleep apnea (OSA) prevalence increases with age, but whether OSA-related sleep disruption could interrupt the processing of previously encoded wake information thought to normally occur during sleep in cognitively normal older adults remains unknown. METHODS:Fifty-two older (age = 66.9 ± 7.7 years, 56 % female), community-dwelling, cognitively normal adults explored a 3D maze environment and then performed 3 timed trials before (evening) and after (morning) sleep recorded with polysomnography (PSG) with a 20-minute morning psychomotor vigilance test (PVT). RESULTS:Twenty-two (22) subjects had untreated OSA (Apnea Hypopnea Index (AHI4%) ≥ 5/hour) where severity was mild on average [median (interquartile range (IQR))] AHI4% = 11.0 (20.7)/hour) and 30 subjects had an AHI4% < 5/hour. No significant differences were observed in overnight percent change in completion time or in the pattern of evening pre-sleep maze performance. However, during the morning post-sleep trials, there was a significant interaction between OSA group and morning trial number such that participants with OSA performed worse on average with each subsequent morning trial, whereas those without OSA showed improvements. There were no significant differences in morning PVT performance suggesting that vigilance is unlikely to account for this difference in morning maze performance. Increasing relative frontal slow wave activity (SWA) was associated with better overnight maze performance improvement in participants with OSA (r= 0.51, p = 0.02) but not in those without OSA, and no differences in slow wave activity were observed between groups. CONCLUSIONS:OSA alters morning performance in spatial navigation independent of a deleterious effect on morning vigilance or evening navigation performance. Relative frontal slow wave activity is associated with overnight performance change in older subjects with OSA, but not those without.

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.