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

Lewy body disorders (LBDs), including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), are the second most common cause of neurodegeneration in older adults. Progressive cholinergic dysfunction is known to be a key contributor to cognitive decline in LBDs, yet accessible biomarkers of cholinergic impairment remain limited. Because cholinergic neurons play a central role in REM sleep and cortical activation, alterations in REM electroencephalographic activity (EEG) may provide a functional marker of cholinergic network integrity in these disorders.Twenty-four participants with DLB, 36 with PD, and 44 controls underwent neuropsychological testing and overnight polysomnography, with a subset completing structural and resting-state MRI. EEG spectral power across δ, θ, α, σ and β frequency bands was quantified during REM sleep and the REM EEG slowing ratio (δ + θ)/(α + σ + β) was derived for frontal, central and occipital regions. Nucleus basalis of Meynert (NBM) volumes were derived from T1-weighted images, and functional connectivity was examined between the NBM and large-scale networks, and between the pedunculopontine nucleus (PPN) and thalamus.DLB participants had greater occipital REM EEG slowing compared with PD and controls. Across LBDs, REM slowing was associated with aberrant nucleus basalis of Meynert connectivity to visual, ventral attentional, default mode, and frontoparietal networks, as well as altered pedunculopontine-thalamic connectivity. Greater REM EEG slowing correlated with worse global cognition and executive function deficits.These findings demonstrate that REM EEG slowing reflects cholinergic network dysfunction and clinically relevant cognitive impairment in LBDs. REM slowing may represent a non-invasive and transdiagnostic biomarker for disease monitoring, prognosis, and stratification in clinical trials.