REM sleep is associated with the integrity of the cholinergic basal forebrain in aMCI participants

Abstract

AbstractBackgroundThe basal forebrain cholinergic system (BFCS) degenerates in Alzheimer’s disease (AD) before the onset of dementia. Interestingly, rapid‐eye movement (REM) sleep is highly dependent on cholinergic activity. In AD patients, REM sleep duration is reduced but the underlying brain mechanisms are still unclear. Our objective was to investigate the associations between REM‐sleep quantity and BFCS integrity in participants with amnestic mild cognitive impairment (aMCI) compared to healthy controls.MethodSixty‐two participants (31 cognitively healthy: 66.8 ± 7.2 years old, 13 women; 31 aMCI: 68.3 ± 8.8 years old, 7 women) underwent polysomnography and structural magnetic resonance imaging examinations. REM sleep duration (number of minutes) and proportion (%) were computed. All participants had a REM sleep apnea‐hypopnea index <15. T1‐weighted images were preprocessed using CAT12 and the DARTEL algorithm, and the mean intensity of BFCS subregions (i.e., Ch1‐2‐3, Ch4 and total BFCS) was extracted using the JuBrain Anatomy Toolbox. Multiple regressions were performed between BFCS subregional intensities and REM sleep indices controlling for age, sex and total intracranial volume, in the whole cohort and in the two groups separately.ResultIn the whole cohort, REM sleep duration and proportion were positively associated with Ch4 intensity (duration: r = 0.31, p = 0.017; proportion: r = 0.35, p = 0.007; Figure 1A and B) and total BFCS intensity (duration: r = 0.31, p = 0.016; proportion: r = 0.29, p = 0.024). Analyses stratified by cognitive status showed the same pattern in aMCI participants: REM sleep duration and proportion were positively associated with both Ch4 intensity (duration: r = 0.44, p = 0.018; proportion: r = 0.49, p = 0.009; Figure 1C and D) and total BFCS intensity (duration: r = 0.46, p = 0.014; proportion: r = 0.46, p = 0.013). No significant association, nor trend, was found in cognitively healthy participants (Figure 1C and D).ConclusionIn aMCI participants, lower REM sleep duration and proportion were associated with a decreased integrity of the BFCS, especially the Nucleus Basalis of Meynert. Our results support the notion that REM sleep alterations are an early marker of the degeneration of the BFCS in prodromal AD, before the onset of dementia.