REM sleep is associated with the volume of the cholinergic basal forebrain in aMCI individuals

Rapid-eye movement (REM) sleep highly depends on the activity of cholinergic basal forebrain (BF) neurons and is reduced in Alzheimer's disease. Here, we investigated the associations between the volume of BF nuclei and REM sleep characteristics, and the impact of cognitive status on these links, in late middle-aged and older participants.

Thirty-one cognitively healthy controls (66.8 ± 7.2 years old, 13 women) and 31 participants with amnestic Mild Cognitive Impairment (aMCI) (68.3 ± 8.8 years old, 7 women) were included in this cross-sectional study. All participants underwent polysomnography, a comprehensive neuropsychological assessment and Magnetic Resonance Imaging examination. REM sleep characteristics (i.e., percentage, latency and efficiency) were derived from polysomnographic recordings. T1-weighted images were preprocessed using CAT12 and the DARTEL algorithm, and we extracted the gray matter volume of BF regions of interest using a probabilistic atlas implemented in the JuBrain Anatomy Toolbox. Multiple linear regressions were performed between the volume of BF nuclei and REM sleep characteristics controlling for age, sex and total intracranial volume, in the whole cohort and in subgroups stratified by cognitive status.

In the whole sample, lower REM sleep percentage was significantly associated to lower nucleus basalis of Meynert (Ch4) volume (β = 0.32, p = 0.009). When stratifying the cohort according to cognitive status, lower REM sleep percentage was significantly associated to both lower Ch4 (β = 0.48, p = 0.012) and total BF volumes (β = 0.44, p = 0.014) in aMCI individuals, but not in cognitively unimpaired participants. No significant associations were observed between the volume of the BF and wake after sleep onset or non-REM sleep variables.

These results suggest that REM sleep disturbances may be an early manifestation of the degeneration of the BF cholinergic system before the onset of dementia, especially in participants with mild memory deficits.