Falgàs Neus, Tort-Colet Núria, Martín-Sobrino Isabel, Mayà Gerard, Peña-González Marta, Rudilosso Salvatore, Gaig Carles, Bosch Beatriz, Arqueros Aurora, Pérez-Millan Agnès, Tort-Merino Adrià, Fernández-Villullas Guadalupe, Piñol-Ripoll Gerard, Balasa Mircea, Lladó Albert, Ruiz Manuel Morales, Muñoz-Moreno Emma, Grau-Rivera Oriol, Iranzo Alex, Grinberg Lea T, Sánchez-Valle Raquel
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Barcelona, Spain.
Universitat de Barcelona, Barcelona, Spain.
Alzheimers Dement. 2026 Feb;22(2):e71183. doi: 10.1002/alz.71183.
Sleep disruption, particularly loss of slow-wave sleep (SWS), is common in Alzheimer's disease (AD), but its neurobiological underpinnings remain unclear. We investigated whether locus coeruleus (LC) integrity relates to SWS across the AD continuum and whether sex and perivascular spaces (PVSs) modify these associations.
In a cohort (11 controls, 30 mild cognitive impairment, 17 AD dementia) we combined overnight polysomnography with LC-sensitive magnetic resonance imaging of the LC, basal ganglia and centrum semiovale PVS ratings, and cerebrospinal fluid noradrenaline. Multivariable linear regression adjusted for demographics, disease stage, and medication use.
Higher LC integrity was associated with greater slow-wave activity and slow oscillation power, with stronger effects in females. Basal ganglia PVS burden was related to lower SWS spectral power, whereas noradrenaline levels were not associated with sleep.
LC integrity, sex, and PVS burden show associations with SWS alterations in aging and AD, supporting restorative sleep as a potential therapeutic target.
睡眠中断，尤其是慢波睡眠（SWS）丧失，在阿尔茨海默病（AD）中很常见，但其神经生物学基础仍不清楚。我们研究了蓝斑（LC）完整性是否与整个AD病程中的SWS相关，以及性别和血管周围间隙（PVS）是否会改变这些关联。
在一个队列（11名对照者、30名轻度认知障碍者、17名AD痴呆患者）中，我们将夜间多导睡眠图与对LC、基底神经节和半卵圆中心PVS评级的LC敏感磁共振成像以及脑脊液去甲肾上腺素相结合。多变量线性回归针对人口统计学、疾病阶段和药物使用情况进行了调整。
较高的LC完整性与更强的慢波活动和慢振荡功率相关，在女性中影响更强。基底神经节PVS负荷与较低的SWS频谱功率相关，而去甲肾上腺素水平与睡眠无关。
LC完整性、性别和PVS负荷与衰老和AD中的SWS改变相关，支持恢复性睡眠作为一个潜在的治疗靶点。
