REM sleep EEG slowing signals basal forebrain integrity in older adults with subjective and mild cognitive impairment

The basal forebrain is an early site of pathology in Alzheimer’s disease (AD). Within this region, the nucleus basalis of Meynert (NbM) provides the primary cholinergic input to the neocortex and supports cortical activation during rapid eye movement (REM) sleep. REM electroencephalography (EEG) slowing is observed in older adults with AD and amnestic mild cognitive impairment (MCI). This study examined the relationship between REM EEG slowing and NbM volume, and whether it differed by cognitive status, sex or sleep apnea severity.

Participants aged ≥60 years with subjective cognitive impairment or MCI underwent neuropsychological and medical assessments, polysomnography and magnetic resonance imaging (MRI). REM EEG slowing was quantified as the ratio of delta and theta (<8Hz) to alpha, sigma and beta (8-32Hz) power. Bilateral NbM and Ch1-3 volume were derived from T1-weighted MRI images. Multiple linear regression and moderation analyses examined associations between REM EEG slowing and NbM volume, adjusting for age, sex, and sleep apnoea severity. To assess anatomical specificity, primary analyses were repeated using Ch1– 3 volume and non-REM EEG slowing. Exploratory analyses examined associations between NbM volume, sleep macroarchitecture, and memory.

The sample comprised 116 participants (59.5% female; mean age = 70.5 years, 64.7% MCI). Greater REM EEG slowing was associated with smaller NbM volume (all p < 0.05), whereas no significant associations were observed with Ch1–3 volume and non-REM EEG slowing (all p > 0.05). Although moderation effects were not significant after FDR correction, within-group analyses suggested a stronger relationship in MCI. Smaller NbM volume was associated with longer sleep latency and poorer episodic memory (all p < 0.05).

REM EEG slowing may reflect early NbM degeneration and provide a non-invasive biomarker of basal forebrain integrity in older adults with cognitive concerns, with findings showing anatomical specificity to the NbM and sleep-stage specificity to REM sleep. Longitudinal studies are required to establish its prognostic value.