Associations between obstructive sleep apnea, Alzheimer’s disease pathology, and objective daytime sleepiness measured by the psychomotor vigilance task in cognitively unimpaired adults

Abstract

AbstractBackgroundDaytime sleepiness is common among individuals with obstructive sleep apnea (OSA), and has been reported among individuals with Alzheimer’s Disease (AD) pathology. However, objective measures of decreased alertness have not been examined in the context of AD. Here, we examined performance on the psychomotor vigilance task (PVT) in relation to AD pathology as indexed by AD biomarkers in cerebrospinal fluid (CSF), among individuals with and without OSA.MethodForty‐eight cognitively unimpaired adults (32 women), mean age 66.3±7.9 years, enrolled in the Wisconsin Alzheimer’s Disease Research Center (ADRC) completed a multifaceted sleep assessment. Presence and severity of OSA was evaluated using WatchPAT at‐home overnight recordings. Habitual sleep‐wake patterns were assessed using actigraphy. Neurobehavioral alertness was quantified using the 10‐minute PVT. CSF biomarkers were quantified using the exploratory Roche NeuroToolKit assays, a panel of automated robust prototype immunoassays (Roche Diagnostics International Ltd). Generalized linear models examined associations between AD biomarkers, apnea‐hypopnea index (AHI), and PVT performance. Primary AD biomarkers of interest were phosphorylated‐tau (p‐tau), total tau (t‐tau), and amyloid‐beta (Aβ) 42/40 ratio, measured in CSF. The primary PVT variable of interest was the mean response time of the 10% slowest responses, which is associated with daytime sleepiness and default mode network activity. Log transformations for PVT and AHI+1 were utilized for analysis. Covariates included age, sex, body mass index, total sleep time, sleep efficiency, APOEε4 status, years of education, and parental history of AD.ResultAHI was associated with lower Aβ 42/40 (β=‐0.005,p=0.03) and higher p‐tau (β=2.22,p=0.03), but not t‐tau (β=20.28,p=0.20). Significant AHI*PVT interactions were observed for p‐tau (p=0.0002) and t‐tau (p=0.02), but not for Aβ 42/40 (p=0.18). Specifically, among individuals with OSA (AHI>5/hour;n=20), PVT performance was correlated with p‐tau (r=0.68,p=0.0009) and t‐tau (r=0.39,p=0.09), an association that was not observed in those without OSA in this preliminary dataset.ConclusionOSA was associated with amyloid and tau pathology, in individuals without cognitive impairment. Furthermore, PVT performance may be an objective measure of sleepiness associated with elevated p‐tau and t‐tau among individuals with OSA. Replication and expansion of these findings in larger and longitudinal datasets are indicated. Funding: Supported by R03AG063274 and P30‐AG062715.