Cholinergic IntegrityCholinergic Integrity in Down Syndrome in Association With Aging, Alzheimer's Disease Pathology, and Cognition

Inclusion Criteria:

1. Diagnosis of Down syndrome (DS), including mosaic DS or partial trisomy 21.
2. Provision of signed and dated informed consent form and if needed, assent with signed consent by a legally authorized representative (LAR).
3. Stated willingness to comply with all study procedures and availability for the duration of the study
4. Male or female, aged 18-55 inclusive.
5. In good general health as evidenced by medical history with no diagnosis of dementia.
6. Permitted CNS-active medications, stable in dose for at least 4 weeks or longer. If new medications have been started, the medical monitoring team will review on case-by-case basis to recommend timing of baseline cognitive testing
7. Adequate visual and auditory acuity to allow neuropsychological testing
8. For females who are not surgically sterile or post-menopausal by two years: negative pregnancy test 24 hours prior to PET scan.
9. Mental Age of 4 years or greater (based upon the Kaufman Brief Intelligence Test, 2nd Edition)
10. English must be first/native language
11. Reliable Study Partner (may be caregiver, sibling, parent) who can provide information about the subject's clinical symptoms and history

Exclusion Criteria:

1. Any significant disease or unstable medical condition that could affect neuropsychological testing (i.e., unstable cardiac problems, chronic renal failure, chronic hepatic disease, severe pulmonary disease)
2. Participants in whom magnetic resonance imaging (MRI) is contraindicated including, but not limited to, those with a pacemaker, presence of metallic fragments near the eyes or spinal cord, or cochlear implant (Dental fillings do not present a risk for MRI)
3. Participants unable to complete MRI and PET procedures
4. IQ less than 40 (as assessed by Kaufman Brief Intelligence Test, Second Edition (KBIT-2).
5. Pregnancy, breast-feeding
6. History within the last 5 years of a primary or recurrent malignant disease with the exception of non-melanoma skin cancers, resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with normal prostate-specific antigen post-treatment
7. Clinically significant abnormalities in B12 or TFTs that might interfere with the study. A low B12 is exclusionary unless follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is not physiologically significant. A high TSH is exclusionary unless follow-up T3/T4 levels indicate that it is not physiologically significant.
8. Clinically significant abnormalities in screening laboratories
9. For participants undergoing CSF collection: a current blood clotting or bleeding disorder, or significantly abnormal PT or PTT at screening or if on anti-coagulation (e.g warfarin)
10. Participants whom the Site PI deems to be otherwise ineligible
11. Clinical diagnosis of dementia
12. Concurrent participation in a clinical trial for an investigational product or concurrent participation in a longitudinal study with overlapping outcome measures/procedures is prohibited