Cholinergic Integrity in Down Syndrome in Association With Aging, Alzheimer's Disease Pathology, and Cognition
Progressive age-related cognitive deficits occurring in both AD and DS have been connected to the degeneration of several neuronal populations, but mechanisms are not fully elucidated. The most consistent neuronal losses throughout the progression of AD are seen in cholinergic neurons where these losses negatively affect cognition, particularly in attention, learning, and memory formation. Evidence of reduced cholinergic integrity in DS is largely limited to animal models and post-mortem human data. The investigators propose to use molecular, functional, and structural biomarkers to assess the cholinergic integrity in adults with DS. The investigators anticipate using the data gathered in this pilot study to inform future study designs to determine AD risk stratification in DS by identifying individuals who show an accelerated decline in cholinergic integrity that correlates with cognitive and neurobehavioral changes. Also, our cholinergic biomarkers may identify whether individuals with DS are likely to respond to pro-cholinergic interventions, including the novel cholinergic modulators that are being developed to enhance cholinergic-sensitive cognitive functioning. The investigators anticipate using the data gathered here to inform future treatment studies in TRC-DS and beyond where novel cholinergic treatments may offer opportunities for early intervention in DS and be complementary to disease-modifying approaches such as anti-amyloid treatments.
• Diagnosis of Down syndrome (DS), including mosaic DS or partial trisomy 21.
• Provision of signed and dated informed consent form and if needed, assent with signed consent by a legally authorized representative (LAR).
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 18-55 inclusive.
• In good general health as evidenced by medical history with no diagnosis of dementia.
• 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
• Adequate visual and auditory acuity to allow neuropsychological testing
• For females who are not surgically sterile or post-menopausal by two years: negative pregnancy test 24 hours prior to PET scan.
• Mental Age of 4 years or greater (based upon the Kaufman Brief Intelligence Test, 2nd Edition)
⁃ English must be first/native language
⁃ Reliable Study Partner (may be caregiver, sibling, parent) who can provide information about the subject's clinical symptoms and history