1008 Daytime Sleepiness Is Associated with Increased Cerebrospinal Fluid Tau Proteins in Alzheimer’s Disease

Abstract Introduction Sleep disturbance increases Alzheimer’s disease (AD) biomarkers, but it remains unclear whether the magnitiude of this effect differs by cognitive status. Addressing this unknown will elucidate when it is most critical to intervene to moderate AD pathophysiology and slow or arrest clinical progression. Methods A total of 155 participants, enrolled in Alzheimer Disease Research Center studies at University of California, Irvine (mean age 72.34 ± 7.07 years, 60.0% female) completed subjective assessment of sleep and cerebrospinal fluid (CSF) collection. Participants were divided into four cognitive status groups (Cognitively Normal, n=89; Questionable Cognitive Impairment, n=19; Mild Cognitive Impairment, n=33; and mild to moderately severe AD dementia, n=14). The Medical Outcomes Study Sleep Scale (MOS-SS) subscales assessed multiple sleep domains: Sleep Disturbance, Sleep Adequacy, Sleep Somnolence, Sleep Problems Index I, and Sleep Problems Index II. CSF biomarkers included β-amyloid 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau181). Moderation by cognitive status on the relationships among sleep scores and CSF biomarkers was assessed using the PROCESS macro in SPSS, adjusting for age and sex. Moderation by sleep scores in the cognitive status-CSF biomarkers relationship was also tested. Results After adjusting for age and sex, moderation analyses revealed significant interactions between sleep somnolence and cognitive status on CSF t-tau (F=3.3, p=0.023) and p-tau181 (F=2.9, p=0.035) but not Aβ42 (F=0.057, p=0.98) protein levels. The associations between sleep somnolence and t-tau (B = 4.18, SE = 1.51, t = 2.76, p = 0.01) and p-tau181 (B = 0.50, SE = 0.18, t = 2.69, p = 0.01) were positive and stronger in the AD group in comparison to all other cognitive status groups (all p>0.35). Conclusion These findings indicate that in AD patients, greater subjective daytime sleepiness is associated with higher levels of t-tau and p-tau181 protein levels. As tau proteins are associated with neurodegeneration and cognitive decline, daytime sleepiness, whether or not due to the presence of sleep disorders such as sleep apnea, may be a risk factor or indicator of symptomatic progression of dementia in AD. Future studies should explore the efficacy of sleep-based interventions in slowing AD dementia progression. Support (if any) NIH K01AG068353, NIH T35AG076424, ADRC P30AG066519