Determining Predictors of Improved Cognitive Function in Children with ASD Between 3 and 6 Years of Age. Which Toddlers Improve?

Background: Longitudinal Investigation of the cognitive development of children with ASD offers a promising way to identify clinically significant subgroups. Here, we focus on cognitive phenotypes, defined by IQ, which constitutes one of the greatest sources of heterogeneity within ASD and is among the strongest predictors of outcome. By leveraging the extensive behavioral data in the APP, we seek to extend past cross-sectional outcome studies that suggest associations between early social motivation, adaptive language functioning, psychopathology and repetitive behaviors, and later cognitive functioning.  

Objectives:   To: (1) present descriptive information about the ASD symptoms, adaptive functioning, and psychopathology measurements in the APP cohort; (2) explore an ASD phenotype derived from IQ-based developmental trajectories during the formative 3 to 6 year period; and (3) examine the association between measurements of social reciprocity, language functioning, attention dysregulation, and repetitive behaviors at 3 years of age and IQ trajectory.

Methods: Participants were 93 individuals with ASD.  To identify cognitive developmental trajectories, the PROC TRAJ macro in SAS was used on an adjusted DQ score derived from the Mullen Scales and the DAS-II. Univariate and multivariate nomial logistic regression models were then employed to investigate unique and composite predictors of trajectory membership using measurements from the ADOS-2, Vineland Adaptive Behavior Scales, Achenbach System of Empirically Based Assessment, and the Repetitive Behavioral Scales-Revised.    

Results:   Three distinct trajectories of intellectual development were identified. The first consisted of individuals with IQs ≤ 75 at both times (Greater challenges: n=34; 37%). The second was comprised of individuals with IQs ≥ 80 at both times (Lesser challenges: n=23; 25%). A third group exhibited IQs < 80 at T1, and had scores of ≥ 80 at T3 with increases of ≥ 1 standard deviation (Changers: n=36; 38%).  Univariate logistic regression showed that more severe ADOS-2 social reciprocity symptoms at T1 predicted membership in the Greater Challenges vs. both Lesser Challenges (odds ratio = 2.00, 95% CI: 1.48 – 2.69) and Changers (odds ratio = 1.44, 95% CI: 1.16 – 1.80) groups (both p <.001). Similarly, children with better language functioning on the T1 Vineland were more likely to be in the Changers (odds ratio = 1.06, 95% CI: 1.02 – 1.11, p <.01) or the Lesser Challenges (odds ratio = 1.15, 95% CI: 1.08 – 1.22, p <.001) versus the Greater Challenges group. Findings remained significant when social reciprocity and language functioning were entered in a multivariate logistic regression model (all p <.03). No associations were found with attention, hyperactivity, and repetitive behaviors.

Conclusions:   The high proportion of young children experiencing robust early cognitive development provides is hopeful for families. It also suggests that low early social reciprocity and adaptive language are risk markers and treatment targets for intensive early intervention. Analyses of the mechanisms of intervention are ongoing. We are also conducting a middle childhood follow-up using behavioral and neuroimaging assays of memory, executive control, language, academic performance, and anxiety to extend the investigation of ASD phenotypes into the understudied, middle childhood period.