PET Measures of CSF Clearance in Preclinical Alzheimer's Disease
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Know the risks and potential benefits of clinical studies and talk to your health care provider before participating.
Read our disclaimer for details.
The purpose of this study is to measure cerebrospinal fluid (CSF) clearance. CSF cushions the brain from impact and carries waste products from the brain to the bloodstream. This process is known as clearance. Researchers have considered that impaired clearance of amyloid (a protein) from the aging brain causes buildup of amyloid in the brain and plays a role in increased risk for Alzheimer's disease. However, until recently, there has not been a method to measure CSF clearance. This study will examine CSF clearance using positron emission tomography (PET) scanning, which creates images of structures in the body and their functioning. This study will also measure the amount of two proteins, tau and amyloid, in the brain. Tau and amyloid are proteins that build up in the brains of people with Alzheimer's disease. An investigational compound (tracer) called [18F]MK-6240 is injected into the blood prior to the scan in order to take images of the CSF clearance and measure tau protein in the brain. This tracer is considered investigational because it is not approved by the US Food and Drug Administration (FDA) for clinical use and is only being used for research purposes.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Layout table for eligibility information
Ages Eligible for Study:
40 Years to 100 Years (Adult, Older Adult)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
This study will involve male and female volunteer subjects from any racial or ethnic group with a diagnosis normal cognition. The base clinical cohort uses the same diagnostic inclusion and exclusion criteria for NL subjects as the NIHADNI protocol. The proposed sample is not intended to be representative of a general population, but it will approximate the samples recruited in NIH and industry sponsored FDA approved clinical trials targeting secondary AD prevention. At this stage of knowledge of human brain CSF clearance, a population based approach was considered premature and over cap funding to support a larger study was not permitted for RFA AG-17-055. Rather, our design uses Aβ enrichment to enable an efficient test of the CSF clearance hypothesis in a clinically relevant group.
Male and female subjects between 40-100 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.
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.
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.