The purpose of this study is to change the concentration of amyloid-beta in human cerebrospinal fluid (CSF) through modulation of the sleep-wake cycle.

The purpose of this research study is to investigate whether or not increasing or decreasing duration of sleep over one night will change the concentration of amyloid-beta in cerebral spinal fluid (CSF).

Inclusion Criteria:

• cognitively normal or CDR 0
• negative for amyloid deposition by PET Pittsburgh Compound-B (PIB) imaging or CSF amyloid-beta-42 concentration
• Age 18-60
• Average reported sleep time 6-10hrs

Exclusion Criteria:

• diagnosis of a sleep disorder such as sleep apnea, narcolepsy, or restless leg syndrome
• positive ambulatory sleep study for obstructive sleep apnea (AHI > 5 respiratory events per hour) that will be performed as part of initial screening prior to enrollment
• Clinical Dementia Rating (CDR) > 0
• tremor or other neurologic injury in the non-dominant upper extremity (such as stroke or tremor) that would prevent the use of actigraphy
• current sleep walking or other sleep parasomnia
• diagnosis and treatment of stroke, myocardial infarction or heart attack,
• coronary artery disease, atrial fibrillation, or congestive heart failure
• diagnosis and treatment of asthma or Chronic Obstructive Pulmonary Disease (COPD)
• diagnosis and treatment of bipolar disorder, major depression, or Schizophrenia
• current urinary or fecal incontinence
• currently on a low salt diet
• diagnosis and treatment of a neurologic disorder such as Parkinson's disease, epilepsy, multiple sclerosis
• currently taking any blood thinner medications such as warfarin, Plavix, or Aspirin
• kidney disease resulting in renal impairment
• liver disease resulting in hepatic dysfunction
• Pregnancy
• currently taking sedating medications such as benzodiazepines
• alcohol use at bedtime
• tobacco use
• BMI >40
• contraindication to lumbar puncture
• diabetes
• sleep schedule outside the range of bedtime: 8pm-12am and waketime 4am-8am
• self reported difficulty sleeping in an unfamiliar environment
• use of sedative-hypnotic medications
• inability to get in and out of bed
• history or presence of any clinically significant medical condition, behavioral or psychiatric disorder, or surgical history based on medical record or patient report
• history of drug abuse within the past 6 months
• positive score on 2 or more categories on the Berlin questionnaire
• participation in another investigational medicinal product or investigational device within the last 30 days

Adverse events were recorded from the start of the participant confinement visits to the Clinical Research Unit when the lumbar catheter was placed and cerebrospinal fluid collected. Adverse event recording continued through a 48 hour telephone follow-up period. Total reporting period was 6 days.