Longitudinal hippocampal and cognitive changes in autism spectrum disorder

/ABSTRACT The prevalence of early-onset dementia is higher in autistic adults than the general population. While there is some evidence that the hippocampus may be smaller in autistic adults, there are no longitudinal studies of hippocampal changes across the lifespan in this population to identify when these differences emerge. Published longitudinal work by our group shows that brain developmental trajectories differ based on modality and region, with some differences present in early childhood and some appearing by late adolescence or early adulthood. This proposal is a first step in establishing lifelong developmental trajectories in autism spectrum disorder (ASD) of brain areas known to be involved in dementia. We will utilize a retrospective dataset collected over 23 years, with up to seven timepoints of data for some participants, in a well-characterized cohort of 125 autistic adults and 150 age-matched non-autistic participants. Our first aim will measure and describe longitudinal changes in hippocampal volume from childhood into adulthood. We will examine total hippocampal volume and hippocampal subregions and use advanced statistical methods that allow for flexible modeling, or unique nonlinear developmental trajectories, separately for participant groups. These methods will identify when group differences emerge in certain regions/subregions, vulnerable windows of development, and regions with persistent group differences. Our second aim will investigate the relationship between hippocampal volume, memory function and longitudinal changes in cognitive performance. We will examine current mental status and how longitudinal hippocampal changes differ in autistic participants who are impaired on dementia screening measures. We will also examine individual trajectories to further characterize aging-related changes within the ASD group. These aims will provide important pilot data for examining an established biomarker for dementia, hippocampal volume and change, throughout adulthood in a population at increased risk. Understanding the interplay between biological and cognitive changes will enable a more accurate characterization of aging and dementia in autistic adults. Consequently, appropriate diagnostic instruments can be developed, and targeted interventions and therapeutics can be implemented to best support autistic adults as they age. Project Number: 1R03AG101228-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: Molly Prigge | Institution: UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH, SALT LAKE CITY, UT | Award Amount: $308,000 | Activity Code: R03 | Study Section: Neurological, Mental and Behavioral Health Study Section[NMBH] View on NIH RePORTER: https://reporter.nih.gov/project-details/11357146