Circadian misalignment and sleep disruption in mild cognitive impairment

Background: While it is evident that Alzheimer s disease is associated with disturbed sleep and circadian rhythms, the extent to which such changes are evident in older people at risk of developing dementia is unknown. Objective: In this study, we aimed to determine whether patients with mild cognitive impairment (MCI) demonstrated significant alterations in the timing of melatonin secretion onset and amount, as well as sleep architecture. Methods: Thirty patients with MCI and 28 age-matched controls underwent psychiatric, medical, and neuropsychological assessment, followed by overnight polysomnography and dim light melatonin onset assessment. Participants also performed an episodic memory task while in the laboratory. Dim light melatonin onset was computed using a standardized algorithm, and area under the curve was computed for melatonin secretion. Sleep architecture measures including wake after sleep onset and latency to rapid eye movement sleep were derived. Results: Patients with MCI had advanced timing of their melatonin secretion onset relative to controls, but the levels of melatonin secreted did not differ between groups. The MCI group also had greater wake after sleep onset and increased rapid eye movement sleep latency. There were differential associations between dim light melatonin onset and cognition between the two groups, with earlier dim light melatonin onset being associated with poorer memory performance in MCI patients. Conclusion: Circadian misalignment and sleep disruption is evident in patients with MCI, and is consistent with changes observed in Alzheimer s disease. Such findings could be a marker for disease trajectory, and may even be implicated in disease pathogenesis