Editors' ChoiceAlzheimer’s Disease

The K-complexes they are a-changin’

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Science Translational Medicine  25 Jan 2017:
Vol. 9, Issue 374, eaal4998
DOI: 10.1126/scitranslmed.aal4998


Reduced frequency of K-complex waveforms on EEG during non-REM sleep may help to differentiate patients with Alzheimer’s disease from older healthy individuals.

Several sleep parameters are known to change in Alzheimer’s disease (AD), although it is unknown whether or not they are a marker of disease progression, a key element in disease pathogenesis, or both. However, some of the findings are contradictory. Increased slow-wave activity on electroencephalography (EEG), for instance, occurs during both wakefulness and sleep in patients with AD. In contrast, a recent study found that a decrease in frontal slow-wave activity during non-rapid eye movement (NREM) sleep was associated with β-amyloid deposition and impaired hippocampal memory consolidation. To address this contradiction, De Gennaro et al. studied frontal K-complexes (<1 Hz frequency) and slow-wave activity (0.6-1 Hz frequency) in 20 patients with AD and 20 healthy age–matched controls during sleep. K-complexes, a waveform with <1 Hz frequency recorded by frontal scalp electrodes on EEG during stage two of NREM sleep, may help to explain this discrepancy because of the frequency overlap between K-complexes and slow-wave activity. The authors hypothesized that changes in the frequency of K-complexes might be better able to discriminate patients with AD from healthy older adults compared with slow-wave activity.

The authors found that patients with AD had a 40% decrease in K-complex density during NREM stage 2 sleep compared with healthy controls. The authors stated that a correct classification of AD was made 80% of the time using K-complex density but not slow-wave activity. AD patients were found to have greater ≤1 Hz slow-wave activity in most cortical areas compared with healthy controls, although this was not significant. There was no decrease in ≤1 Hz slow-wave activity over the frontal areas in patients with AD, but this was the same location that K-complex density was noted to decrease. Last, multiple regression analysis revealed that a reduction in K-complex density predicted cognitive impairment.

The findings of De Gennaro et al. suggest that a decrease in the number of K-complexes during NREM sleep will better help to differentiate patients with AD from healthy older adults compared with slow-wave activity. A major limitation of this study is that it cannot answer the question of whether or not decreased K-complex density is a marker for AD progression. As AD progresses, there may be changes in slow-wave activity during sleep that are best determined using longitudinal rather than cross-sectional studies. Future studies will be needed to establish whether there is a causal relationship between changes in K-complex density and AD progression.

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