Exploring the Link Between Sleep and Brain Clearance

Study Overview
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Brief Summary
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The purpose of this study is to assess the link between sleep and the clearance of waste products from the brain. This will be assessed in a group of healthy older adults.

Detailed Description
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First, the investigators want to assess the relationship between sleep parameters and markers for brain clearance, assessed with MRI and blood samples. Second, the investigators want to probe whether associations can be influenced by modulation of sleep parameters by means of auditory stimulation.

Official Title
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Biomarkers of Brain Clearance During Sleep

Conditions
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Healthy Aging

Intervention / Treatment
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* Behavioral: Auditory Stimulation
* Behavioral: Sham (no stimulation)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participation in previous longitudinal cohort studies at the study site Ability to provide written and verbal informed consent Fluency in the German language Stable home situation that allows for reliable application of the intervention for the duration of the study Ability to apply the intervention for the duration of the study, either alone or with support from a co-habitant For women: Hormonal contraception, if menstrual cycle is still present or has been present within a year Good general health status, normal cognitive function Exclusion Criteria: Failure or inability to give informed consent Inability to follow the procedures of the investigation For women: pregnancy or breastfeeding Presence of sleep disorders (e.g. sleep apnoea, narcolepsy, restless leg syndrome, insomnia, REM sleep disorder) Shift-work or a home situation that requires several awakenings during the night (e.g. newborn) History of serious illness likely to interfere with study outcomes Presence or history of a diagnosed neuropsychiatric illness Current diagnosis of uncontrolled or poorly controlled diabetes Current cancer of the brain or unstable cancer undergoing treatment Evidence of serious atherosclerotic cardiovascular disease

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Auditory Stimulation<br>Auditory Stimulation during sleep | Behavioral: Auditory Stimulation<br>* enhancement of sleep slow wave activity through acoustic stimulation<br>|
| Sham Comparator: No Auditory Stimulation<br>Playing no tones during sleep but still recording brain activity | Behavioral: Sham (no stimulation)<br>* Playing no tones during sleep but still recording brain activity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between EEG slow wave activity (uV) and cerebrospinal fluid flow (ml/min) from phase contrast MRI |  | 2 weeks | 
| Correlation between EEG slow wave activity (uV) and diffusivity (mm2/s) from diffusion MRI |  | 2 weeks | 
| Correlation between EEG slow wave activity (uV) and perfusion (ml/min/100 ml) from arterial spin labelling MRI |  | 2 weeks | 
| Correlation between EEG slow wave activity (uV) and beta-amyloid (pg/ml) |  | 2 weeks | 
| Correlation between EEG slow wave activity (uV) and tau (pg/ml) |  | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between EEG slow wave activity (uV) and fatigue, assessed via the fatigue severity scale (FSS) questionnaire |  | 2 weeks | 
| Correlation between EEG slow wave activity (uV) and sleepiness, assessed with the Epworth Sleepiness Scale questionnaire |  | 2 weeks | 
| Correlation between EEG slow wave activity (uV) and memory function, assessed with the Hopkins Verbal Learning Test (memory score) |  | 2 weeks | 
| Correlation between EEG slow wave activity (uV) and attention, assessed with the Trail Making Test (time to completion) |  | 2 weeks | 
| Correlation between EEG slow wave activity (uV) and C-Reactive Protein (mg/L), assessed from a blood sample |  | 2 weeks | 
| Correlation between EEG slow wave activity (uV) and TNF-alpha (pg/L), assessed from a blood sample |  | 2 weeks | 
| Correlation between EEG slow wave activity (uV) and interleukins (pg/L), assessed from a blood sample |  | 2 weeks | 
| Correlation between EEG slow wave activity (uV) and executive function (summary score, dimensionless) |  | 2 weeks | 
| Correlation between EEG slow wave activity (uV) and neuro-metabolite levels (mmol) from magnetic resonance spectroscopy |  | 2 weeks |