Consistent with NOT-OD-22-137, Availability of Administrative Supplements for the INCLUDE Project, we propose to recruit 500 adults with Down syndrome (DS) aged 18-39 in the mid- Atlantic area to create a cohort, per Component 2: “Assembly of a large cohort of individuals with Down syndrome across the lifespan to perform deep phenotyping and study co-existing conditions.” Our Co-Investigator, Dr. Capone, at the Kennedy Krieger Institute (KKI), has data dating back ~25 years on >500 individuals with DS who were then children (3-17yrs) and are now adults. He also has data on an additional ~1,000 who were seen as adults (18-35yr) whom we will recontact for purposes of enrollment. From all 500 participants, we will collect demographic data and next of kin contact information for enrollment in future studies, and we will request releases of medical records from outside of KKI. This registry will be used to enroll participants in a future R01, which, like the parent award (R01AG075996; MPIs Spira & Maher), will investigate the association of antibodies to common infections (HSV- 1, HSV-2, CMV, EBV, TOX, SARS-CoV-2) in blood with cognitive and functional outcomes, mild cognitive impairment (MCI-DS) and dementia diagnoses, blood-based AD biomarkers, and measures of accelerated biological aging in persons with DS. If we cannot recruit 500 participants from among Dr. Capone’s former participants, we will expand through the mid-Atlantic region via mailing lists, clinics, schools, social media, and snowball sampling. We will prioritize recruitment of participants from Dr. Capone’s KKI database with existing data from childhood on medical conditions, psychiatric disorders, cognitive/adaptive function, and sleep data from polysomnography. This work is a supplement to Wave 5.5 of the Baltimore Epidemiologic Catchment Area (ECA) Study, which is investigating associations of common infections with cognitive and functional outcomes, MCI and dementia diagnoses, blood-based AD biomarkers, and measures of accelerated biological aging in that cohort.

Project Narrative Alzheimer’s disease is a public health crisis with no disease-modifying treatment, so prevention is key to reducing its prevalence. The proposed research will elucidate the extent to which infection with Herpes Simplex Virus Types 1 and 2, Cytomegalovirus, Epstein-Barr Virus, Toxoplasma gondii—measured four times over ~25 years—and SARS-CoV-2 (the virus that causes COVID-19) are associated with subsequent cognitive and functional decline and diagnoses of mild cognitive impairment and dementia, measures of Alzheimer’s disease pathology from blood samples, and accelerated biological aging. Results will advance our understanding of whether common infections increase the risk for Alzheimer’s disease and related dementias and how they might do so.