Donders Institute for Brain, Cognition and Behaviour
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Thesis defense Sharon Ooms (Donders series 343)

30 November 2018

Promotor: prof. dr. M. Olde-Rikkert
co-promotors: dr. J. Claassen, dr. ir. M. Verbeek

Sleep well, age well? Assessing sleep disruption as a player in Alzheimer’s disease pathogenesis

Motivated by the lack of evidence in humans, this work investigates how poor sleep in midlife affects the risk of Alzheimer’s disease and the pathophysiological mechanism behind it. To this end, we conducted a series of studies to gather cumulative evidence on the effect of sleep deprivation on CSF Aβ in humans, including examining alternatives to commonly observed challenges in its measurement.
As a first step, we performed a study to investigate the effect of one night of total sleep deprivation on CSF Aβ and tau in healthy male volunteers. One night of total sleep deprivation in 26 healthy middle-aged volunteers showed an increase in CSF Aβ42 (but not Aβ40 or tau) the following morning, while a night of sleep showed a 6% decrease in Aβ. This study showed that sleep deprivation, or prolonged wakefulness, seems to interfere with the normal physiological morning decrease in CSF Aβ42 in humans, as has previously already been shown in rodent studies. As a next step, we wanted to investigate the specific contribution of slow wave sleep on CSF Aβ in humans, as slow wave sleep is associated with a period of diminished neuronal firing and is expected to be associated with less Aβ production. For this purpose, we developed an automated protocol which disrupts slow wave sleep with the aid of auditory tones. This protocol was used to disrupt SWS in healthy volunteers to measure the specific effect of slow wave sleep on CSF Aβ. Specific disruption of slow wave sleep correlated with an increase in Ab40. This effect was specific for slow wave sleep, and not for total sleep duration or sleep efficiency. Furthermore, home sleep quality calculated from the average of 6 nights preceding lumbar punctures, was associated with higher tau.

Another important unexplored topic in the field is the effect of chronic sleep deprivation in humans, which has been proven difficult due to the heterogeneity that exists within populations with sleep disorders. A well-defined working population (maritime pilots) with irregular sleep due their profession enabled us to properly investigate the effects of chronic poor sleep in mid-life on cognition. Although the main focus of this thesis has been on the relationship between poor sleep in mid-life and the risk for Alzheimer’s disease, we conclude this thesis by elaborating on the treatment methods of several sleep disorders in patients already burdened with dementia.