*2.1. Participants and Procedure*

All procedures were reviewed and approved by the Institutional Review Boards at participating institutions (New York State Institute for Basic Research in Developmental Disabilities, Columbia University Irving Medical Center, Massachusetts General Hospital, the University of California at Irvine, The Johns Hopkins University Schools of Medicine and Public Health, and the University of North Texas Health Science Center). Informed consent was obtained from participants or their legally authorized representatives along with participant assent. The current analyses included data from 144 adults with DS, ranging from 40 to 81 years of age, who were enrolled in a larger, multidisciplinary program of research focused on biomarkers of AD in adults with DS. Only the participants assessed in New York, New York (*n* = 43); Boston, Massachusetts (*n* = 56); and Irvine, California (*n* = 46) were administered the full neuropsychological battery that is reported in this study. Therefore, participants assessed at other sites could not be included in the current set of analyses. Inclusion criteria included (1) age ≥ 40, (2) estimated preexisting IQ > 30, (3) absence of significant sensory or motor impairments, and (4) willingness to provide a routine blood sample for studies of fluid-based biomarkers of AD.

Participants received a comprehensive evaluation at study baseline that included (a) a review of medical records; (b) physical and neurological evaluations; (c) interviews with knowledgeable informants focused on cognitive and functional abilities, health-related condition and medical history, and neuropsychiatric concerns; and (d) direct one-on-one testing with a core battery developed specifically for assessing dementia status in adults with intellectual disabilities. The full direct testing battery required approximately 1.5 to 2 h to complete. None of the participants in the larger, multidisciplinary program of research with severe ID had valid scores on all 22 measures; therefore, this subgroup was not included in the current study.
