Understanding sleep-wake alterations in Alzheimer’s Disease

Sleep-wake alterations, such as sleep fragmentation and daytime sleepiness, are early signs of Alzheimer's disease (AD). The locus coeruleus is one of the brainstem nuclei that contributes to the regulation of arousal and wakefulness via noradrenergic control. Interestingly, locus coeruleus is one of the first brain regions affected by AD. Recently, a growing interest in developing neuroimaging tools to detect these early AD-related changes in locus coeruleus has arisen, given its potential as a diagnostic biomarker sensitive to early disease stages.

However, little is known regarding how locus coeruleus changes directly contribute to early symptoms in Alzheimer's disease, including dysregulation of sleep-wake circuits in humans. Therefore, our aim is to determine the relationship between locus coeruleus and sleep-wake alterations in AD. We hypothezise that the degeneration of LC would be associated with sleep and wake disturbances in AD patients. One hundred patients aged under 75 with mild dementia due to Alzheimer's disease, as confirmed by cerebrospinal fluid biomarkers, will be recruited in Alzheimer's Unit - Hospital Clínic de Barcelona. All participants will undergo a specific neuroimaging sequence optimized to detect locus coeruleus changes. A cross-sectional evaluation with validated and self-reported questionnaires will assess sleep and wake alterations. Additionally, a subset of forty participants will undergo objective measures of sleep-wake alterations, namely overnight video-polysomnography and one-week actigraphy monitoring. The present project is critical to better understand the role of locus coeruleus degeneration in the development of sleep and wake alterations in AD, highlight their assessment as early diagnostic tools and promote the noradrenergic system as a target for tailored treatments.