PET Measures of CSF Clearance in Preclinical Alzheimer's Disease

Inclusion Criteria:

- Male and female subjects between 40-85 years old will be enrolled. Younger subjects
are not included as the risk for brain amyloid lesions is too low

- All subjects will speak English as their first language or demonstrate proficiency in
English (defined as reaching a scaled score of > 11 on the WAIS vocabulary test).

- All subjects will have normal cognition at baseline: a Clinical Dementia Rating CDR=0,
Global Deterioration Scale GDS<2.

- All subjects will be in good general health and able to participate in the LP and
imaging exams. This determination is made by the study neurologist and reviewed at a
consensus meeting for each subject.

Exclusion Criteria:

- Uncontrolled hypertension or metabolic disease

- Neurodegenerative disorders (i.e. Parkinson disease. LBD, or FTD).

- Dementia or Mild cognitive impairment at baseline

- Long life major depression. Baseline scores ≥16 on the 17-item Hamilton Depression
Scale at baseline.

- Long-life DSM-IV axis 1 disorders.

- Mental retardation.

- Substance abuse.

- Concurrent medication limiting validity of neuropsychological tests or imaging.

- Anti-depressants with anti-cholinergic properties

- Monoamine oxidase inhibitors (MAOi)

- Regular use of narcotic analgesics (>2 doses per week).

- Use of neuroleptics

- Use of anti-dementia medications (Aricept, Exelon, Razadyne) and memantine (Namenda))
or anti-Parkinsonian medications (Sinemet, amantadine, bromocriptine, pergolide,
selegeline).

- Individuals taking over the counter memory enhancing or protecting medications (e.g.
ginkgo biloba, vitamins) are not excluded.

- Implanted medical devices that are incompatible with MRI imaging.

- Radiation exposures exceeding annual Rad Worker limits.

- Heart failure stage D as defined by American Heart Association (7).

- Chronic kidney disease in stages ≥ 4, as defined per National Kidney Foundation (8).

- Brain tumor and other neoplastic disorders outside the brain where disease itself or
its treatment (radiation, chemotherapy) is likely to affect brain structure or
function.

- Stroke when meeting criteria for total anterior, partial anterior or posterior
circulation infarct according to the Oxford Community Stroke Project classification.
Patients with clinically silent of lacunar strokes and transient ischemic attacks will
not be excluded.

- Significant head trauma.

- Hydrocephalus.

- Hostility or refusal to cooperate