Abstract
Down syndrome (DS) predisposes individuals to a wide range of cognitive outcomes, with some individuals
acquiring more advanced cognitive skills and others demonstrating severe or profound levels of intellectual
disability (S/PID). The early origins of S/PID in individuals with DS are poorly understood, and individuals with
DS and S/PID are often underrepresented in the scientific literature. This project will address an important gap
in our knowledge and establish a novel account of variability in cognitive skill acquisition in DS with an emphasis
on understanding those children who demonstrate the most pronounced levels of early cognitive delay. We will
characterize early cognitive growth in young children with DS and examine the association between
severe/profound early cognitive delays and behavior, biomedical factors, and molecular biosignatures known to
be affected by DS, such as various inflammatory processes, elevated neurodegeneration and neuroinflammation
biomarkers, dysregulation of the growth hormone (GH)-IGF1 axis, and dysregulated metabolism. To achieve
this goal, we will recruit 90 children with DS to be assessed at three data waves (Wave 1 = 12 months; Wave 2 =
24 months; Wave 3 = 36 months) and we will conduct comprehensive cognitive and broader developmental
evaluations. Blood samples will be collected concurrently with each visit and biomedical history information will
be obtained. We will then model latent growth trajectories along early cognitive and other developmental
domains and examine the association between growth profiles, biomedical history, molecular biosignatures, and
severe/profound degrees of early cognitive delay at Wave 3. This integrated approach to characterizing
heterogeneity in cognitive delays in DS can potentially transform the nature of treatments and interventions for
those individuals who are in need of the most intensive degree of lifelong community support.