Faculty Bibliography

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.

RATIONALE/BACKGROUND:) may reduce discomfort in those with high nasal resistance and improve adherence in this subgroup. OBJECTIVES/OBJECTIVE:improves adherence over CPAP in subjects with high nasal resistance. METHODS:versus CPAP in World Trade Center dust-exposed subjects with OSA stratified by nasal resistance measured by 4-Phase Rhinomanometry. RESULTS:(mean Δ hours (95% CI)) in subjects with low resistance (0.33h (-0.10, 0.76)) or high nasal resistance (0.26h (-0.14, 0.66)). No significant differences were observed in any of the secondary outcomes between PAP modes. CONCLUSIONS:than to CPAP in subjects with high or low nasal resistance, and, show clinically insignificant better adherence overall with CPAP. Clinical Trial registered with Clinicaltrials.gov (NCT01753999).

BACKGROUND:Sleep difficulties are common among older adults, and clinical management of sleep difficulties commonly includes sleep medication (pharmacological and non-pharmacological). Our research examines sleep medication use and incident dementia over 8 years using nationally representative data from older adults ages 65 years and older in the United States. METHODS:We used data collected from the National Health and Aging Trends Study (NHATS), a nationally-representative longitudinal study of Medicare beneficiaries. Routine sleep medication use (pharmacological and non-pharmacological) was defined as use "most nights" or "every night." Participants were screened for dementia with validated instruments that assessed memory, orientation, and executive function. We conduct prospective analyses to examine the relationship between routine sleep medication use and incident dementia using Cox proportional hazards modeling and estimated survival curves. Analyses controlled for age, sex, marital status, education, and chronic conditions. RESULTS:Among respondents at baseline (n = 6373), most participants (21%) were age 70-74 years of age. Participants were 59% female and the sample comprised non-Hispanic White (71%). At baseline, 15% of our study sample reported using sleep medication routinely, which is representative of 4.6 million older adults in the US. Covariate adjusted proportional hazard models revealed that routinely using sleep medication was associated with incident dementia (HR = 1.30, 95%CI: 1.10 to 1.53, p < 0.01). CONCLUSIONS:Our study observed, in a nationally representative study of older adults in the US across 8 years of data that 15% of older adults report routinely using sleep medication, yet routine use of sleeping medication was associated with incident dementia across the follow-up interval. Future research may examine behavioral approaches to improving sleep among older adults.

Background: Rodent model and in vitro studies suggest brain temperature has the potential to bidirectionally interact with tau pathology in Alzheimer's Disease (AD): tau phosphorylation is robustly increased by small (<1degreeC) reductions in temperature within the human physiological range, and lower brain thermoregulatory areas may be among those first affected by AD pathology. Here, we evaluated the cross-sectional association between body temperature (Tb), as a proxy for brain temperature, and clinically accessible markers of tau pathology in cognitively normal older adults.
Method(s): Tb was measured continuously over 48 hours with ingestible telemetry combined with a novel pre-processing algorithm. This period included 2 nights of nocturnal polysomnography to facilitate delineation of Tb-tau pathology relationships according to waking vs sleeping time intervals. Tau pathology was assessed with both soluble markers including plasma P-tau (P-tau 181) and cerebrospinal fluid (CSF) P-tau, both sampled the following day, and aggregated tau, namely neurofibrillary tangle (NFT) burden in early (I-III) Braak stage areas imaged with MR-PET using the [18F]MK-6240 radio tracer on average ~ one month later Results: Plasma and CSF P-tau levels were highly correlated with one another and with tau tangle radio tracer uptake (NFT burden), p < 0.05 for all comparisons. Lower Tb (quantified by lower mean Tb and a greater proportion of time Tb was under 37.0degreeC) was associated with increased NFT burden and increased plasma and CSF P-tau levels, p < 0.05 all comparisons. For aggregated tau, lower Tb - tau pathology associations were seen during for Tb recorded during waking, but not during sleeping intervals.
Conclusion(s): Preliminary results suggest that lower body temperature in older adults may be associated with increased aggregated and soluble tau pathology

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.

STUDY OBJECTIVES/OBJECTIVE:In a randomized controlled trial, we compared the effect of the Tailored Approach to Sleep Health Education (TASHE) on obstructive sleep apnea (OSA) self-efficacy among community-dwelling blacks in New York City. METHODS:Study participants were 194 blacks at high risk for OSA based on the Apnea Risk Evaluation System. TASHE intervention was delivered via a Wi-Fi-enabled tablet, programmed to provide online access to culturally and linguistically tailored information designed to address unique barriers to OSA care among blacks. Blacks in the attention-controlled arm received standard sleep information via the National Sleep Foundation website. Blacks in both arms accessed online sleep information for 2 months. Outcomes (OSA health literacy, self-efficacy, knowledge and beliefs and sleep hygiene) were assessed at baseline, at 2 months, and at 6 months. RESULTS:We compared outcomes in both arms based on intention-to-treat analysis using adjusted Generalized Linear Mixed Modeling. TASHE exposure significantly increased OSA self-efficacy (OSA outcome expectation [ß = 0.5, 95% CI: 0.1-0.9] and OSA treatment efficacy [ß = 0.4, 95% CI: 0.0-0.8]) at 2 months, but not at 6 months. Additionally, TASHE exposure improved sleep hygiene at 6 months (ß = 6.7, 95% CI: 2.2-11.3), but not at 2 months. CONCLUSIONS:Community-dwelling blacks exposed to TASHE materials reported increased OSA self-efficacy compared to standard sleep health education. Stakeholder-engaged, theory-based approaches, as demonstrated in the TASHE intervention, can be used successfully to deliver effective sleep health messages. CLINICAL TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov identifier NCT02507089.