The homeostasis of NREM Slow Wave Activity in Alzheimer's disease and Mild Cognitive Impairment

Introduction: The modulation of delta EEG activity between evening and morning wakefulness is considered an indirect marker of the regulation of the homeostatic sleep need, and it has been recently found altered in patients with Alzheimer's disease (AD) and individuals with Mild Cognitive Impairment (MCI). This finding points to an alteration of the homeostatic process during sleep in AD/MCI and suggests an impact of the neurodegenerative process on the homeostatic regulation of NREM Slow Wave Activity (SWA). Therefore, the aim of this study is to assess overnight changes in NREM SWA topography in AD/MCI patients, comparing these groups with healthy controls (HC). Method: 44 AD (17 M; 73 ± 7.02 y), 50 MCI (25 M; 72 ± 6.80 y), and 48 HC (29 M; 69 ± 6.26 y) performed a single night of polysomnographic recording (19 EEG derivations, EOG, and EMG). The spectral power of the frequency bins in the SWA range (0.5–4.75 Hz) during NREM sleep was computed. Then, the ratio between the first and the second half of the night during NREM sleep has been assessed in each cortical derivation on each SWA frequency bin. One way analysis of variance (ANOVA) was performed to compared macrostructural variables and overnight changes in NREM SWA activity between AD, MCI, and HC. Results: A significant difference between groups on the 1st versus 2nd half of the night ratio of NREM SWA was found at 2 Hz in right parieto-occipital derivations, at 3 Hz in temporal, parietal, and occipital locations, and at 4 Hz in frontal, temporal, parietal, and occipital derivations. In all these frequency bins and locations, AD and MCI individuals showed reduced overnight changes in NREM SWA compared with HC, without differences between the clinical groups. Conclusion: The present finding suggests local alterations of the homeostatic regulation of NREM SWA in MCI/AD patients. Such alterations appear stable in different stages of the disease and specific for areas particularly involved in AD pathology and high-frequency delta activity (2–4 Hz). Future studies should replicate this result and describe its possible relationship with AD biomarkers.