Study links locus coeruleus status to deep sleep quality in aging and Alzheimer's disease

The study, published in Alzheimer's & Dementia has identified that the integrity of the locus coeruleus —a brainstem structure involved in regulating the wake-sleep cycle— is associated with better deep sleep quality in healthy individuals and patients across the Alzheimer's disease spectrum. The findings also reveal sex differences and the involvement of cerebral vascular factors.

The locus coeruleus, a small region of the brainstem that plays a key role in controlling the wake-sleep cycle, is one of the first areas where beta-amyloid accumulates in Alzheimer's disease. Therefore, studying its integrity can help detect and understand very early changes in the disease.

The study was coordinated by Neus Falgàs, first author and researcher in the IDIBAPS Alzheimer's Disease and Other Cognitive Disorders Group, and member of the Clínic's Alzheimer's and Other Cognitive Disorders Unit, together with Raquel Sánchez-Valle, Clínic's medical director, head of the research group, and last author. Dr. Núria Tort-Colet, second author of the study and postdoctoral researcher at the BBRC, led the analysis of sleep data in close collaboration with Neus Falgàs.

Alzheimer's disease and sleep disturbances

Alzheimer's disease is a progressive neurodegenerative disorder affecting memory and other cognitive functions. One of its frequent symptoms is sleep disturbances, particularly reduced slow-wave sleep —the deepest, most restorative phase essential for memory processes and brain health. Until now, only preclinical studies, such as those in animal models, had suggested that the locus coeruleus plays a role in deep sleep regulation through noradrenaline production.

Previous Clínic-IDIBAPS studies had already shown that the status of this nucleus is associated with the severity of neuropsychiatric symptoms, including sleep problems. This study goes further by analyzing specific deep sleep parameters.

Relationship between deep sleep, brain structure, and vascular factors

To understand how these elements interact, the research team analyzed nighttime brain activity (polysomnography) from 58 participants (healthy individuals, those with mild cognitive impairment, and dementia due to Alzheimer's disease) and correlated it with markers obtained through neuroimaging techniques and biomarkers. This integrated approach enabled simultaneous assessment of sleep quality, locus coeruleus status, and various indicators of vascular and glymphatic health (the brain's drainage/cleaning system).

The results show that individuals with a better-preserved locus coeruleus exhibited higher slow-wave activity, a clear indicator of higher-quality deep sleep. "This relationship was particularly strong in women, suggesting possible biological or hormonal differences in sleep regulation," explains Neus Falgàs.

Additionally, a greater presence of perivascular spaces in the basal ganglia —a marker of cerebral vascular health— was associated with reduced slow-wave activity. This combination of findings demonstrates that deep sleep quality may be influenced by both the status of sleep-regulating structures and the health of cerebral blood vessels.

“Detailed sleep analysis allowed us to objectively and non-invasively quantify the quality of deep sleep, beyond sleep stages,” explains Dr. Núria Tort-Colet. “Sleep plays a key role in brain function and can be a relevant clinical indicator in Alzheimer's disease.”

Future perspectives

According to the research team, these results reinforce the importance of deep sleep for brain health and suggest that interactions between the locus coeruleus, vascular factors, and sex may influence Alzheimer's disease progression.

Longitudinal studies are needed to determine whether preserving locus coeruleus function or improving vascular health can help maintain sleep quality and potentially modulate disease course.

Collaborative spirit

The work results from collaboration between teams from the Alzheimer's and Other Cognitive Disorders Unit, the Functional Testing Section, and the Cerebral Vascular Pathology Unit of the Neurology Service, with support from IDIBAPS's Neuroimaging Platform. At BBRC, we have actively contributed to data analysis and interpretation of results, reinforcing our commitment to translational research and understanding the mechanisms involved in brain aging and Alzheimer's disease. Collaborators such as Mayo Clinic Florida have also participated.

Reference article:

Falgàs N, Tort-Colet N, Martín-Sobrino I, Mayà G, Peña-González M, Rudilosso S, Gaig C, Bosch B, Arqueros A, Pérez-Millan A, Tort-Merino A, Fernández-Villullas G, Piñol-Ripoll G, Balasa M, Lladó A, Ruiz MM, Muñoz-Moreno E, Grau-Rivera O, Iranzo A, Grinberg LT, Sánchez-Valle R. Relationship between locus coeruleus and slow-wave sleep in aging and Alzheimer's disease. Alzheimers Dement. 2026 Feb;22(2):e71183. https://doi.org/10.1002/alz.71183