PET scan to image PDE4B in people with Alzheimer’s disease or mild cognitive impairment

* INCLUSION CRITERIA:

Participants will be referred by a physician with the suspected diagnosis of AD or MCI. However, the PI of this protocol will provide the final diagnosis. For this reason, this protocol will have just one consent form for participants suspected of having either AD or MCI.

AD and MCI Study Groups:

Participants must meet all the following criteria:

* 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.
* Have had their radial artery pulse checked for the presence of adequate ulnar collateral flow and the absence of any metal or foreign objects in both wrists.
* Agree to adhere to the lifestyle considerations.

Healthy Volunteers:

Participants must meet all the following criteria:

* Aged 50 or older.
* Able to provide informed consent.
* Be in good general health, as evidenced by medical history and physical examination, and have no cognitive impairment.
* Have had their radial artery pulse checked for the presence of adequate ulnar collateral flow and the absence of any metal or foreign objects in both wrists.
* Agree to adhere to the lifestyle considerations.

EXCLUSION CRITERIA:

Both the study groups will be excluded if they meet any of the following criteria:

* 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).
* Are unable to travel to the NIH.
* Have recent exposure to radiation related to research (e.g., PET from other research) that, when combined with this study, would be above the allowable limits.
* Have an inability to lie flat and/or lie still on the camera bed for at least two hours, including claustrophobia, overweight greater than the maximum for the scanner, and uncontrollable behavioral symptoms, which will be screened by an interview with the volunteer and/or caregiver during the screening visit.
* Participants must not have substance use disorder or alcohol use disorder.
* Participants should not be under treatment or previously treated with an amyloid antibody such as lecanemab.
* Are unable to have an MRI scan (e.g., because of pacemakers or other implanted electrical devices, brain stimulators, dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pumps, shrapnel fragments, or metal fragments in the eye).
* Pregnancy or breast feeding.
* HIV infection.
* Non-English speaking participants.

Exclusion of Children:

Inclusion of children is not appropriate, because this protocol has more than minimal risk from radiation exposure without the possibility of direct benefit.

Exclusion of Pregnant or Breastfeeding Women:

Pregnant women will be excluded because this protocol involves exposure to ionizing radiation. Lactating women will be excluded because radioisotopes may be excreted in milk. We will not require contraception for this protocol to allow participants autonomy in medical decision-making. However, while we will not require contraception for woman of childbearing potential, we will perform a pregnancy test at screening and prior to all procedures to ensure participants are not pregnant

Exclusion of Participants who are HIV Positive:

Persons with HIV infection are excluded because HIV infection itself may change cAMP signaling.

Exclusion of Non-English-Speaking Participants:

Non-English-speaking participants will be excluded from participation in this study because neuropsychological testing is required by this protocol. This testing, which is critical for interpreting study results, has not been validated in other languages or when using a translator.