Brain Sleep Clearance of Amyloid-Beta Peptides

Inclusion Criteria: Group A:

• Male and female subjects with normal cognition and 55-75 years of age

• Newly recruited or recruited on the follow-up evaluation from an existing longitudinalcohort of 180 normal elderly already enrolled in an active study (R01HL118624-01). Group B:

• Male and female subjects with normal cognition and 30-75 years of age

• Recruited from the MSSM where there are already studies ongoing aimed at determiningthe consequence of disrupting REM sleep via CPAP withdrawal on the consolidation ofspatial navigational memory (PI. Dr. Varga).

• Previously diagnosed moderate-severe SDB patients and on active CPAP treatment. Group A + B:

• All subjects will be within normal limits on neurological and psychiatricexaminations.

• All subjects enrolled will have both a Clinical Dementia Rating (CDR)<0.5 and GlobalDeterioration Scale (GDS)<3 (i.e. cognitively normal).

• All subjects will have an informed family member or life partner interviewed toconfirm the reliability of the subject interview.

• All subjects will agree to the MRI imaging, the lumbar puncture (s), apolipoprotein E (ApoE) genotyping and DNA banking.

B. Exclusion Criteria:

• Diagnosis of any brain disease or MRI evidence of brain damage including significanttrauma, hydrocephalus, seizures, mental retardation or other serious neurologicaldisorder (e.g. Parkinson's disease or other movement disorders). Persons with silentcortical infarcts will be excluded. White matter lesions will not be exclusions.

• History of brain tumor or contraindications for LP.

• Prior history of post-LP headache.

• Significant history of alcoholism or drug abuse.

• History of major psychiatric illness (e.g., schizophrenia, bipolar or life longhistory of major depression)

• Geriatric Depression Scale >7 (for subjects > 55 y/o) or Beck Depression Inventory >18 (for subjects <55 y/o)

• Current pregnancy or intent to become pregnant during the period of study.

• Evidence of clinically relevant and uncontrolled cardiac (unstable and untreatedcoronary or peripheral artery disease), pulmonary (ventilatory failure, Cheyne-Stokesbreathing, severe and inadequately controlled arterial hypertension, acute upperrespiratory infection), untreated hypothyroid or uncontrolled hematologicalconditions. Insulin dependent diabetes and/or history of treated hypertension are notexclusions. Normal subjects with current levels of HbA1c >5.9% or diabetics >7.0%and/or current blood pressure levels >140/90 mm Hg will be advised to seek referral.

• Physical impairment of such severity as to adversely affect the validity ofpsychological testing.

• Any prosthetic devices (e.g., pacemaker or surgical clips) that constitutes a hazardfor MRI imaging.

• History of a first-degree family member with early onset AD (< age 60) dementia.

• Prior bariatric surgery within 6 months or are currently participating in a medicalweight loss program.

• Irregular sleep-wake rhythms (based on one week at home monitoring with actigraphy)

• Inability to avoid the use of alcohol, caffeine during the 48h before the NPSG .

• Patients that are professional vehicle drivers or train operators, or patients thathave had a previous motor vehicle accident related to sleepiness and cannot rest theday of the LP after the sleep deprivation experiment.

• Conditions that alter normal sleep patterns: Irregular sleep-wake rhythms (based onone week at home monitoring with actigraphy) or moderate to severe SDB (AHI4%>15 perhour) .

• Medications adversely affecting cognition or sleep will result in exclusion. Theexcluded medications include:

• Narcotic analgesics (>2 doses per week).

• Chronic use of medications with anticholinergic activity.

• Anti-Parkinsonian medications (carbidopa/levodopa, amantadine, bromocriptine,pergolide, selegeline).

• Others: amphetamines, amphetamine-like compounds, appetite suppressants,phenothiazines, reserpine, buspirone, clonidine, disulfiram, guanethidine, MAOinhibitors, theophylline, tricyclic antidepressants, salicylates, cholinesteraseinhibitors and memantine.