Brain Amyloid- Retention During Wakefulness and Following Emergence From Sleep in Healthy People

Background: Brain activity creates waste products. The body s glymphatic system removes this waste, especially during sleep. One brain waste product is amyloid-beta (Ab). It plays a role in Alzheimer s disease. Researchers want to study the effect of sleep on Ab in the brain. Objective: To see if sleep affects the amount of waste product removed from the brain. Eligibility: Healthy people at least 18 years of age. Design: Participants will be screened with a medical history, physical exam, and blood and urine tests. They will answer questions about drug use, psychiatric history, and family history of alcoholism or drug use. Participants will complete an MRI screening questionnaire. Participants will stay in the clinic overnight two times. On one night they will sleep through the night. On the other night they will be kept awake all night. These overnight visits can happen in any order. Participants will wear 2 activity monitors, on the wrist and the ankle. Participants will have positron emission tomography (PET) scans. A small amount of a radioactive chemical will be injected through an intravenous (IV) catheter. Participants will lie on a bed that slides into the scanner. A cap or a special mask may be placed on the participant s head. Participants will have magnetic resonance imaging (MRI) scans. The MRI scanner is a metal cylinder in a strong magnetic field. Participants will lie on a table that slides into the cylinder. A device called a coil will be placed over the head. Participants will do a task on a computer screen in the scanner. Participants will have tests of thinking, memory, and attention. They may be interviewed, complete questionnaires, take pen-and-paper or computer tests, and perform simple actions.

Objective: To assess if there are differences in \[18F\]florbetaben uptake following the first 120 minutes of its injection (reflecting amyloid-beta or Ab load and/or docked Ab) in subjects during rested wakefulness (RW) after normal sleep compared to wakefulness after 24 hrs of sleep deprivation (SD). Specifically, we hypothesize that during RW after a normal night s sleep there will be less \[18F\]florbetaben binding measured as distribution volume ratios (DVR) in precuneus relative to cerebellum (reflecting normal brain clearing of Ab overnight) when compared to wakefulness after SD, which would interfere with Ab removal from the brain s interstitial space. Though we will be measuring Ab in whole brain our analysis will focus in precuneus since this is the brain region that shows the higher levels of Ab accumulation in contrast to cerebellum where there is no accumulation of Ab. Therefore, overall Ab load in precuneus (as reflected by \[18F\]florbetaben DVR) will be lower during RW compared to SD. MRI and 1H-MRS will be used secondarily to assess if there are differences in connectivity, function and neurochemistry in precuneus between RW and SD. Because the rate of CSF production as well as Ab clearance from CSF differs as a function of age the current study will also allow us to assess if the higher Ab brain levels reported in older than in younger individuals reflect greater Ab clearance in younger than older individuals. Study population: Two groups consisting of healthy young adults (18 - 40 years of age) and healthy older adults (\>40 years of age). Males and females will be included. Design: Observational study. We will complete testing in 15 healthy controls in each group for a total of thirty subjects (n=30) to assess the brain uptake of \[18F\]florbetaben (scan done for 120 minutes following tracer injection). The order of the scans (RW vs SD will be randomized). MRI scans will be obtained either before or after the PET scanning session done following \[18F\]florbetaben injection. Outcome measures: Uptake of \[18F\]florbetaben in the brain will be measured after RW and after SD. Primary outcomes will be differences in uptake and clearance of \[18F\]florbetaben in precuneus (reflecting A beta load and/or docked A beta) in subjects after SD compared to after RW as measured with distribution volume ratios using cerebellum as reference region and that clearance of Ab brain (difference between RW and SD) will be greater in younger than in older participants . We hypothesize that Ab load in precuneus \[18F\]florbetaben DVR) will be higher after SD than RW and that this difference will be larger for younger than older participants. We also predict that older individuals will have higher brain accumulation of Ab than younger ones. In addition we will assess differences in mean water diffusivity in brain, lactate concentration, functional connectivity at rest and functional activation during an attention task between RW and SD conditions. We predict lower fMRI signals in dorsal attention network (DAN) during attention task, lower functional connectivity in the default mode network (DMN), and lower functional connectivity and mean diffusivity for SD than for RW. We further predict higher concentration of lactate, a marker of anaerobic metabolism for SD than for RW. As exploratory analysis we will also assess based on the scans obtained after RW if individuals with higher brain Ab accumulation will have worse cognitive performance on neuropsychological tests than those with low brain Ab.