Age-related Changes in Sleep-wake Regulation

Study Overview
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Brief Summary
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A sleep deprivation protocol combined with state-of-the-art, simultaneous positron emission tomography and magnetic resonance spectroscopy imaging will be employed to investigate the effects of sleep deprivation and aging on hypothesized molecular markers of sleep need.

Official Title
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Age-related Changes in Sleep-wake Regulation: Effects of Sleep Loss on Possible Molecular Markers of Sleep Need

Conditions
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Sleep Deprivation

Intervention / Treatment
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* Behavioral: Prolonged wakefulness


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy male individuals age: 20-35 or 60-70 years right-handed non-smokers moderate caffeine/alcohol consumption normal BMI Exclusion Criteria: Sleep/circadian rhythms disturbances former brain injuries with loss of consciousness and brain anomalies drug intake/consumption medication intake cardiac pacemaker neurological disorders prior participation (during past 2 years) in radiological or nuclear experiment

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sleep deprivation young men<br>Young study participants will complete four nights in the sleep laboratory, whereas they will stay awake during one night. PET brain imaging will be conducted at the same circadian time on three consecutive afternoons (prior, during and after prolonged wakefulness). Additionally, validated tests of vigilance and cognitive performance will be administered and the brain waves will be recorded in wakefulness and sleep. | Behavioral: Prolonged wakefulness<br>* 40 hours of prolonged wakefulness<br>|
| Experimental: Sleep deprivation older men<br>Older study participants will complete four nights in the sleep laboratory, whereas they will stay awake during one night. PET brain imaging will be conducted at the same circadian time on three consecutive afternoons (prior, during and after prolonged wakefulness). Additionally, validated tests of vigilance and cognitive performance will be administered and the brain waves will be recorded in wakefulness and sleep. | Behavioral: Prolonged wakefulness<br>* 40 hours of prolonged wakefulness<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep-wake induced change in cerebral availability of mGluR5 (metabotropic glutamate receptors of subtype 5) | Positron emission tomography | Change from baseline metabotropic glutamate receptors of subtype 5 availability after 33 hours of prolonged wakefulness and 8 hours of recovery sleep | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep-wake induced change in glutamate concentration in prefrontal cortex and basal ganglia | Magnetic resonance spectroscopy | Change from baseline glutamate concentration after 33 hours of prolonged wakefulness and 8 hours of recovery sleep | 
| Sleep-wake induced change in potential molecular markers of sleep need | microRNAs, fragile X mental retardation protein, and brain-derived neurotrophic factor concentrations in peripheral blood | Change from baseline microRNA, fragile X mental retardation protein and brain-derived neurotrophic factor concentrations after 33 hours of prolonged wakefulness and 8 hours of recovery sleep | 
| Sleep-wake induced change in sleep electroencephalogram (EEG) | Spectral composition of the EEG during sleep | Change from all-night baseline sleep EEG in 8 hours of recovery sleep after 33 hours of prolonged wakefulness | 
| Sleep-wake induced change in waking electroencephalogram (EEG) | Spectral composition of the EEG in wakefulness | Change from baseline waking EEG during 33 hours of prolonged wakefulness and after 8 hours of recovery sleep | 
| Sleep-wake induced change in subjective state | Subjective sleepiness as quantified with the Stanford Sleepiness Scale (range: 1 to 7) | Change from baseline sleepiness during 33 hours of prolonged wakefulness and after 8 hours of recovery sleep | 
| Sleep-wake induced change in cognitive performance | Cognitive performance battery including tasks measuring sustained attention, executive functioning and working memory | Change from baseline cognitive performance during 33 hours of prolonged wakefulness and after 8 hours of recovery sleep | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Positron emission tomography, Magnetic resonance spectroscopy, Aging