Exploring the Role of Sleep in Alzheimer’s Disease: the AlfaSleep Project

AbstractBackgroundSleep disruption is prevalent in the aging population and increasingly recognized as a risk factor and an early sign of Alzheimer’s disease (AD). Emerging data suggest that dysregulated orexin signaling may play a role in this association. The AlfaSleep study aims to characterize sleep patterns with objective measurements, and determine CSF orexin‐A levels in cognitively unimpaired middle‐aged adults at increased risk of AD.MethodTwo‐hundred cognitively unimpaired middle‐aged adults from the prospective observational ALFA+ study have been invited to participate in this study based on their cerebrospinal fluid (CSF) biomarker profile at the ALFA+ study baseline (100 in the AD continuum and 100 control, non‐altered biomarkers). ALFA+ participants are followed‐up every three years (and currently are undergoing the first follow‐up visit) with neuropsychological testing, blood and CSF sampling, and MRI and PET (with FDG, amyloid and tau tracers) acquisition. Participants included in the AlfaSleep study are additionally characterized with actigraphy (Actiwatch2®, Philips Respironics during two weeks), a nasal flow monitoring device (RUSleeping RTS®, Philips Respironics during one night) and CSF orexin‐A measurements. Furthermore, a subset (n = 90) will undergo overnight polysomnography at the Hospital Clinic Sleep Unit (Figure 1). Sleep‐related outcomes include total sleep time, sleep latency, sleep efficiency, sleep fragmentation, apnea‐hypopnea index and sleep microarchitecture measures (e.g. spectral power analyses). These data, as well as CSF orexin‐A levels will be compared across participants with different AD biomarkers profiles and correlated with cognitive performance, neuroimaging and fluid biomarkers data.ResultTo date, 134 participants (mean age 64.4 years, 67% female) have been included in the AlfaSleep study. Of these, 50 (37.9%) reported poor sleep quality (PSQI>5), 45.5% are APOE‐ε4 carriers and 35.8% had abnormal CSF amyloid levels, as measured at the ALFA+ baseline visit (see Table 1 for a detailed description).ConclusionDue to its multimodal approach, and the profile of the study population (cognitively unimpaired middle‐aged adults in the AD continuum), the present project will make relevant contributions to understand the role of sleep disruption as a risk factor and early clinical manifestation of AD. Preliminary results will be presented at the conference.