Disruption of sleep macro- and microstructure in Alzheimer’s disease: overlaps between neuropsychology, neurophysiology, and neuroimaging

Abstract Alzheimer’s disease (AD) is the leading cause of dementia, often associated with impaired sleep quality and disorganized sleep structure. This study aimed to characterize changes in sleep macrostructure and K-complex density in AD, in relation to neuropsychological performance and brain structural changes. We enrolled 30 AD and 30 healthy control participants, conducting neuropsychological exams, brain MRI, and one-night polysomnography. AD patients had significantly reduced total sleep time (TST), sleep efficiency, and relative durations of non-rapid eye movement (NREM) stages 2 (S2), 3 (S3), and rapid eye movement (REM) sleep ( p < 0.01). K-complex (KC) density during the entire sleep period and S2 ( p < 0.001) was significantly decreased in AD. We found strong correlations between global cognitive performance and relative S3 ( p < 0.001; r = 0.86) and REM durations ( p < 0.001; r = 0.87). TST and NREM stage 1 (S1) durations showed a moderate negative correlation with amygdaloid and hippocampal volumes ( p < 0.02; r = 0.51–0.55), while S3 and REM sleep had a moderate positive correlation with cingulate cortex volume ( p < 0.02; r = 0.45–0.61). KC density strongly correlated with global cognitive function ( p < 0.001; r = 0.66) and the thickness of the anterior cingulate cortex ( p < 0.05; r = 0.45–0.47). Our results indicate significant sleep organization changes in AD, paralleling cognitive decline. Decreased slow wave sleep and KCs are strongly associated with cingulate cortex atrophy. Since sleep changes are prominent in early AD, they may serve as prognostic markers or therapeutic targets.