Electroencephalographic slowing during REM sleep as a marker of cholinergic network dysfunction in Lewy body disorders

Lewy body disorders (LBD), including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), are the second most common cause of neurodegeneration in older adults. Dysfunction of cholinergic brainstem and forebrain pathways, including the pedunculopontine nucleus (PPN) and nucleus basalis of Meynert (NBM), has been implicated in cognitive decline in LBD, yet accessible functional markers remain limited. Because REM sleep depends on ascending cholinergic pathways, alterations in REM electroencephalographic (EEG) activity may provide a window onto their integrity. Twenty-four participants with DLB, 36 with PD, and 44 controls underwent neuropsychological testing and polysomnography, with a subset completing structural and resting-state MRI. EEG spectral power across δ, θ, α, σ and β bands was quantified during REM sleep and the REM EEG slowing ratio (δ + θ)/(α + σ + β) derived for frontal, central and occipital regions. NBM volumes were derived from T1-weighted images, and functional connectivity examined between the NBM and large-scale networks, and the PPN and thalamus. DLB participants had greater occipital REM EEG slowing than PD and controls, a regionally specific rather than global effect. Across LBD, REM slowing was most robustly associated with PPN–thalamic connectivity, with weaker NBM connectivity and no NBM volume association. Greater occipital REM EEG slowing correlated with worse global cognition and executive function. These findings demonstrate that occipital REM EEG slowing reflects PPN–thalamic and, to a lesser extent, NBM network dysfunction, is associated with clinically relevant cognitive impairment in LBD, and may represent a non-invasive, transdiagnostic marker for disease monitoring, prognosis, and stratification in clinical trials.