Exploring cognitive and biological correlates of sleep quality and their potential links with Alzheimer's disease (ALFASleep project). Protocol for an observational study

Fauria, Karine; Minguillón, Carolina; Sánchez Benavides, Gonzalo; Arenaza Urquijo, Eider M.; Suárez-Calvet, Marc; Gispert, Juan Domingo; Grau, Oriol (Grau Rivera)

doi:http://dx.doi.org/10.1136/bmjopen-2022-067159

Exploring cognitive and biological correlates of sleep quality and their potential links with Alzheimer's disease (ALFASleep project). Protocol for an observational study

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Fauria K, Minguillon C, Knezevic I, Tort-Colet N, Stankeviciute L, Hernández L, et al. Exploring cognitive and biological correlates of sleep quality and their potential links with Alzheimer's disease (ALFASleep project). Protocol for an observational study. BMJ Open. 2022 Dec 30; 12(12): e067159. DOI: 10.1136/bmjopen-2022-067159

Abstract

Introduction: the growing worldwide prevalence of Alzheimer's disease (AD) and the lack of effective treatments pose a dire medical challenge. Sleep disruption is also prevalent in the ageing population and is increasingly recognised as a risk factor and an early sign of AD. The ALFASleep project aims to characterise sleep with subjective and objective measurements in cognitively unimpaired middle/late middle-aged adults at increased risk of AD who are phenotyped with fluid and neuroimaging AD biomarkers. This will contribute to a better understanding of the pathophysiological mechanisms linking sleep with AD, thereby paving the way for the development of non-invasive biomarkers and preventive strategies targeting sleep. Methods and analysis: we will invite 200 participants enrolled in the ALFA+ (for ALzheimer and FAmilies) prospective observational study to join the ALFASleep study. ALFA+ participants are cognitively unimpaired middle-aged/late middle-aged adults who are followed up every 3 years with a comprehensive set of evaluations including neuropsychological tests, blood and cerebrospinal fluid (CSF) sampling, and MRI and positron emission tomography acquisition. ALFASleep participants will be additionally characterised with actigraphy and CSF-orexin-A measurements, and a subset (n=90) will undergo overnight polysomnography. We will test associations of sleep measurements and CSF-orexin-A with fluid biomarkers of AD and glial activation, neuroimaging outcomes and cognitive performance. In case we found any associations, we will test whether changes in AD and/or glial activation markers mediate the association between sleep and neuroimaging or cognitive outcomes and whether sleep mediates associations between CSF-orexin-A and AD biomarkers. Ethics and dissemination: the ALFASleep study protocol has been approved by the independent Ethics Committee Parc de Salut Mar, Barcelona (2018/8207/I). All participants have signed a written informed consent before their inclusion (approved by the same ethics committee). Study findings will be presented at national and international conferences and submitted for publication in peer-reviewed journals.