Preliminary findings of accelerated visual memory decline and baseline brain correlates in middle-age and older adults with autism: The case for hippocampal free-water

Abstract

Research aimed at understanding cognitive and brain aging in adults with autism spectrum disorder (ASD) is growing, but critical longitudinal work is scant. Adults with ASD struggle with tasks involving visual memory compared with neurotypical adults (NT). This may be related to differences in size or integrity of the hippocampus and its’ primary structural connectivity pathway, the fornix. The aim of this study was to describe preliminary findings of longitudinal aging trajectories in short- and long-term visual memory abilities in middle-age and older adults with ASD, compared with matched NT adults. We then evaluated baseline multi-modal imaging metrics of the hippocampal system, including the relatively novel metric of free-water, as potential correlates of longitudinal memory change in the ASD group. Middle-age and older adults with ASD (n = 25) and matched NT adults (n = 25) between the ages of 40 and 70 years were followed longitudinally at ~2-year intervals (range 2–5 years). Participants completed the Wechsler Memory Scale III Visual Reproduction task. Longitudinal mixed models were utilized to detect group differences in memory change with baseline age and sex as covariates. Hippocampal volume was measured via T1-weighted MRI images with FreeSurfer. Fornix fractional anisotropy and hippocampal and fornix free-water were measured from diffusion tensor imaging scans. Exploratory correlations were run between individual hippocampal system metrics and longitudinal slopes of visual memory change. There was a significant group by time interaction for long-term visual memory, such that middle-age and older adults with ASD declined faster than matched NT adults. There was no group by time interaction for short-term visual memory. Baseline hippocampal free-water was the only hippocampal system metric that correlated with long-term visual memory change in the ASD group. As one of the first longitudinal cognitive and brain aging studies in middle-age and older adults with ASD, our findings suggest vulnerabilities for accelerated long-term visual memory decline, compared to matched NT adults. Further, baseline hippocampal free-water may be a predictor of visual memory change in middle-age and older adults with ASD. These preliminary findings lay the groundwork for future prognostic applications of MRI for cognitive aging in middle-age and older adults with ASD.

Cortico-basal ganglia white matter microstructure is linked to restricted repetitive behavior in autism spectrum disorder

“…To our knowledge, this work is the first to assess microstructure of intra-basal ganglia white matter pathways (i.e., SN to putamen, GPe to STN) in ASD and how such pathways relate to expression of RRB. This study is also among the first to quantify FW or implement free-water correction of DTI data in ASD [ 20 , 21 ].…”

“…Quantification of free-water or corresponding correction of DTI scalars has had limited application in ASD research [ 20 , 21 ]. It is possible that prior evaluations of basal ganglia white matter in ASD using FA as an outcome measure were impacted by partial volume effects of extracellular free-water.…”

“…The FW measure itself has already demonstrated significant value in a variety of neurodegenerative disorders and it is hypothesized that abnormal FW values are associated with atrophy and/or inflammation [ 14 – 19 ]. Despite the widespread use of DTI to study connectivity in ASD, FW quantification and correction have had limited application in this population [ 20 , 21 ]. Many of the brain regions and white matter tracts hypothesized to be involved in the expression of RRB in ASD are proximal to the ventricular system, and as such, FW quantification may be of great value to DTI research in ASD.…”

Increased anticholinergic medication use in middle‐aged and older autistic adults and its associations with self‐reported memory difficulties and cognitive decline

“…Some longitudinal work provides evidence for parallel cognitive aging across a range of measures, including verbal and visual recall, working memory, and prospective memory, among autistic and non‐autistic adults, suggesting that autistic adults neither show increased nor decreased risk for age‐related cognitive decline relative to non‐autistic adults (Torenvliet et al, 2023). Other longitudinal studies, however, suggest that a subset of middle‐aged and older autistic adults evidence steeper age‐related decline (relative to non‐autistic adults) in long‐term visual memory (Walsh et al, 2022) and short‐term verbal memory (Pagni et al, 2022). These differences in findings may be related to differences in sample size or methods across the studies.…”

APOE ε4-Allele in Middle-Aged and Older Autistic Adults: Associations with Verbal Learning and Memory

“…ASD and Alz share similar symptoms, such as cognitive and communicative impairment, insomnia, weak muscular interaction, and speech and hearing challenges [11,12]. In a series of two publications, our research group recently showed preliminary longitudinal findings that MA+ autistic adults demonstrate accelerated short-term memory, long-term memory, and hippocampal volume loss, compared to matched NT adults [13,14]. Taken together, MA+ autistic adults may have increased vulnerability towards accelerated cognitive decline and increased risk for developing Alz compared to NT adults.…”