Sleep‐like slow waves during resting‐state: A promising EEG biomarker of amyloid and neurodegeneration in preclinical Alzheimer's disease

INTRODUCTION: Growing evidence supports a critical role of sleep slow waves (SW) in Alzheimer's disease (AD). However, wake SW (sleep-like SW potentially reflecting local intrusions of sleep) remain unexplored in AD. METHODS: A total of 274 older adults with subjective cognitive decline (SCD) (INSIGHT-preAD cohort, 76.6 ± 3.5 years) underwent (i) positron emission tomography (PET) scans for amyloid (A) and neurodegeneration (N), (ii) high-density resting-state electroencephalogram (EEG) recordings to detect wake SW, and (iii) cognitive assessments. PET biomarkers were reassessed 2 years later. We examined wake SW associations with (1) current A/N status, (2) cognition, and (3) amyloid conversion. RESULTS: A+N-, A-N+, and A+N+ individuals exhibited lower delta wake SW density than A-N- participants. Wake SW amplitude (1) was higher in A+N+ than A-N- individuals, (2) correlated with poorer memory, and (3) predicted A- to A+ conversion (n = 157 A- stable individuals, n = 16 convertors). DISCUSSION: Wake SW represent promising early EEG biomarkers for AD pathology and amyloid conversion, facilitating risk stratification before cognitive decline onset.