CNS*2026 Halifax

Introduction

There has been recent evidence to suggest that autistic adults have higher risk of neurodegenerative disease and dementia compared to non-autistic adults [1]. Previous studies have found some age-related brain differences between autistic and non-autistic adults, but how these differences may contribute to increased dementia risk remain unclear. We used a combination of network analysis and partial least squares to identify functional and structural connectivity patterns that correlate with long-term memory decline in both autistic (n=40) and non-autistic (n=33) adults using data from a longitudinal study.


Methods

We obtained T1, diffusion, and functional MRI data. Brain networks with 96 regions of interest were constructed using the CONN [2] and TVB-UKBB [3] pipelines for functional and structural connectivity from participants’ first scan. Long-term memory change was measured using the slope of a mixed effects model for the delayed recall (A7) score of the Auditory Verbal Learning Test evaluated 2-5 times across 2-9 years of follow-up. Networks were thresholded and quantified with the Brain Connectivity Toolbox in MATLAB [4]. Network measures were residualized using age and sex as covariates. Behavioral partial least squares was used to identify multivariate correlations between network measures and long-term memory outcomes [5].



Results

For the non-autistic adults, there was a significant latent variable relationship between structural connectivity and long-term memory change; weaker structural connectivity in classic memory regions (e.g. hippocampus) correlated with greater memory decline. The autistic adults showed significant latent variable relationships between functional connectivity and long-term memory change; weaker, less interconnected, and less organized functional connectivity across the whole brain correlated with greater memory decline. For both cases, there was a significant difference between groups for the latent variable relationship, demonstrating differing relationships between connectivity and memory.



Discussion
Both the autistic and non-autistic adults showed significant relationships between connectivity and memory decline. We found that, for the non-autistic adults, memory decline was related to structural connectivity patterns that involved classic memory regions (e.g. hippocampus). For the autistic adults, memory decline was related to functional connectivity patterns across the whole brain. These findings suggest the potential for unique MRI based biomarkers to identify increased risk of accelerated memory decline in autistic adults.


References

1. Starkstein, S., Gellar, S., Parlier, M., Payne, L., & Piven, J. (2015). High rates of parkinsonism in adults with autism. J. Neurodev. Disord.
   
2. Whitfield-Gabrieli, S., & Nieto-Castanon, A. (2012). Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks. Brain connectivity.
   
3. Frazier-Logue, N., Wang, J., Wang, Z., Sodums, D., Khosla, A., Samson, A. D., ... & Shen, K. (2022). A robust modular automated neuroimaging pipeline for model inputs to TheVirtualBrain. Front. Neuroinform.
   
4. Rubinov, M., & Sporns, O. (2010). Complex network measures of brain connectivity: uses and interpretations. Neuroimage.
   
5. Krishnan, A., Williams, L. J., McIntosh, A. R., & Abdi, H. (2011). Partial Least Squares (PLS) methods for neuroimaging: a tutorial and review. Neuroimage.
   

Acknowledgement
We would like to acknowledge funding sources for our project, the National Institute on Aging [P30 AG072980], the National Institute of Mental Health [R01MH132746; K01MH116098], the Department of Defense [AR140105], and the Arizona Biomedical Research Commission [ADHS16-162413].