Background:
About 5 million adults in the United States have age-related brain disorders. These include Alzheimer disease (AD), mild cognitive impairment (MCI), and other dementias. The number of people with these disorders will likely increase as the population ages and life span increases. Inflammation is thought to play a role in AD and MCI. Researchers want to know if an enzyme called PDE4B increases inflammation in people with AD or MCI.
Objective:
To test whether medical imaging using a new radiotracer (\[18F\]PF-06445974) can measure PDE4B in the brains of people with AD or MCI.
Eligibility:
People aged 50 years and older with AD or MCI. Healthy volunteers are also needed.
Design:
Participants will have up to 5 clinic visits with 3 imaging scans of the brain.
They will have be screened. They will have a physical exam with blood tests. This will include tests of their heart and nerve function, including memory.
Participants will have 2 positron emission tomography (PET) scans. One will use a standard radiotracer. The other will use the study radiotracer. They will receive each tracer through a tube attached to a needle inserted into a vein. During the scan with the study tracer, participants will have a second tube inserted into a vein in the wrist; this tube will be used to draw blood during the scan. Participants will lie on a bed that slides into a doughnut-shaped machine. These visits will take about 6 hours each.
Participants will have 1 magnetic resonance imaging (MRI) scan. They will lie on a bed that slides into a cylinder. This visit will take up to 2 hours....
Aged 50 or older.
Be able (or have their Legally Authorized Representative (LAR) be able) to understand the study and be willing to sign a written informed consent document.
Have been diagnosed by a neurologist or psychiatrist with MCI or AD.
Be in good general health as evidenced by medical history and physical examination.
Clinically significant abnormalities on EKG or laboratory testing. This includes CBC and acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen).
Participants should not have taken non-steroidal anti-inflammatory drugs (NSAIDs) for two weeks prior to the PET scan. Aspirin, corticosteroids (with the exception of skin products), or immunosuppressants (e.g., methotrexate) must not have been taken in the prior month.
Have other major neurological or medical diseases that may cause cognitive dysfunction, such as structural brain diseases, metabolic diseases, paraneoplastic syndromes, infectious diseases, or other significant neurological abnormalities.
Have an unstable medical condition that, in the opinion of the investigators, makes participation unsafe (e.g., an active infection or untreated malignancy).
National Institute of Mental Health (NIMH)
Lead sponsor