. Association of Excessive Daytime Sleepiness With Longitudinal β-Amyloid Accumulation in Elderly Persons Without Dementia. JAMA Neurol. 2018 Jun 1;75(6):672-680. PubMed.

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  1. This study is a nice addition to a growing body of research, both animal and human, that links amyloid and sleep. Carvalho et al. found that self-reported excessive daytime sleepiness was associated with longitudinal amyloid accumulation measured with [C11]PiB PET.

    Strengths of the study include the fact that participants were well-characterized and the analysis controlled for factors that may affect amyloid accumulation and/or risk for Alzheimer's dementia, including midlife physical activity, cardiovascular risk factors such as obesity and diabetes, as well as depression. Furthermore, the study was sizeable for a longitudinal PET study, including 283 participants.

    An outstanding question is whether amyloid accumulation precedes sleep abnormalities, or sleep changes are the result of AD-associated brain changes, even at the preclinical stage of the disease. Data in animals suggest that the relationship is likely bidirectional, with disrupted sleep affecting amyloid accumulation, and amyloid accumulation in turn affecting sleep. In this study, restricting the analysis to participants who were amyloid-positive at baseline revealed an even stronger relationship between excessive daytime sleepiness and amyloid accumulation over time, hinting that perhaps a bidirectional process may already be at play. Additional studies are needed to determine whether treating sleep disorders early may mitigate amyloid accumulation, or could slow amyloid accumulation in people who are already amyloid-positive.

    View all comments by Barbara Bendlin
  2. This is a very interesting study in JAMA Neurology by Vermuri and colleagues, showing a link between excessive daytime sleepiness (EDS) and longitudinal accumulation of Aβ. As stated by the authors, EDS is likely a consequence of disruption of night-time sleep patterns, and thus adds to the growing literature supporting the link between poor sleep and increased risk for Alzheimer’s disease—particularly the relationship between poor sleep and increased brain Aβ burden. This work, in a quality longitudinal cohort, adds further support to previous work from other highly characterised longitudinal studies of aging, such as the Australian Imaging, Biomarker, and Lifestyle (AIBL) study. Previous studies in AIBL have reported associations of suboptimal sleep characteristics (determined by PSQI) and increased brain Aβ burden (Brown et al., 2016). Together these studies add further weight to the exploration of potential mechanisms that mediate the relationship between suboptimal sleep and brain Aβ burden. One such suggested mechanism is the glymphatic system (Iliff et al., 2012), which functions during sleep and would likely be significantly affected by poor sleep. Supporting the potential importance of the glymphatic system in this relationship is our recently published study that shows moderation of the sleep-Aβ-burden relationship by genetic variation in the Aquaporin-4 (AQP4) gene (Rainey-Smith et al., 2018). AQP4 encodes a water-channel protein located in the astrocytic end feet and is believed to be a key component of the glymphatic system. Overall, the growing body of literature strongly indicates that potentially addressing suboptimal sleep, through intervention strategies, warrants further investigation. Further, the potential that there is genetic moderation of these relationships is also of significant interest as it could allow for more individualised interventions.

    References:

    . The Relationship between Sleep Quality and Brain Amyloid Burden. Sleep. 2016 May 1;39(5):1063-8. PubMed.

    . A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med. 2012 Aug 15;4(147):147ra111. PubMed.

    . Genetic variation in Aquaporin-4 moderates the relationship between sleep and brain Aβ-amyloid burden. Transl Psychiatry. 2018 Feb 26;8(1):47. PubMed.

    View all comments by Stephanie Rainey-Smith
  3. I find this study to be very interesting and I'm looking forward to see what doors it can open for future research.

    View all comments by Lucian Hodoboc

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