Association of glymphatic dysfunction, free water, white matter integrity and long-term memory performance in aging autistic adults

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Zhang, Y., Ofori, E., Chen, K., Harker, S. A., Velez, M., Gallegos, S. M., Grabeel, K., Johnson, F., Baxter, L., Woodruff, B., & Braden, B. B. (2026). Association of glymphatic dysfunction, free water, white matter integrity and long-term memory performance in aging autistic adults. Molecular Autism, 17(1), 10-10. https://doi.org/10.1186/s13229-026-00705-4

Journal or book title
Molecular Autism
Publisher
Springer Science and Business Media LLC
Volume
17
Issue
1
Pages
10-10
Article number
10
Publication date: 18 Feb 2026 Added to AutiHub: 7 Aug 2026 Type: Article Article language: English
Publisher source (DOI) OpenAlex source

This publication is integrated into AutiHub through:

Authors

Publication authors
11
Publication authors identified as autistic
2 / 11 (18.2%)
  1. Yuanchao Zhang
  2. Edward Ofori
  3. Kewei Chen
  4. Samantha A. Harker *
  1. Manuela Velez
  2. Stephen M. Gallegos *
  3. Katie Grabeel
  4. Faith Johnson
  1. Leslie Baxter
  2. Bryan Woodruff
  3. B. Blair Braden

Abstract

BACKGROUND: Autistic adults are at elevated risk of accelerated cognitive aging and Alzheimer’s disease and related dementias (ADRD), yet the underlying neurobiological mechanisms remain poorly understood. Dysfunction in the glymphatic system—a brain-wide network responsible for clearing waste via interstitial fluid flow—may contribute to this vulnerability by promoting extracellular free water (FW) accumulation and white matter (WM) degeneration. METHODS: A total of 113 autistic and 90 age- and sex-matched neurotypical (NT) adults (aged 18–71 years) underwent multimodal MRI scanning and episodic memory assessments. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, alongside FW maps, and fractional anisotropy (FA) maps were computed for each participant. Group comparisons, correlations, and mediation analyses were performed. RESULTS: Autistic adults showed significantly lower DTI-ALPS values, higher fornix FW, lower fornix FA, and poorer episodic memory scores compared to NT adults. Age-related hippocampal FW accumulation was more pronounced in autistic adults. Mediation analyses revealed that fornix FW mediated the relationship between DTI-ALPS and both fornix FA and hippocampal FW. Long-term episodic memory scores correlated with fornix FA, as well as whole-brain gray matter FW and WM FA in autistic adults. LIMITATIONS: The cross-sectional design precludes causal inference regarding glymphatic function, free water accumulation, WM integrity, and cognition. In addition, our sample was not evenly balanced by sex and excluded individuals with co-occurring intellectual disability, which may limit generalizability to the broader autistic population. CONCLUSIONS: Our results suggest that glymphatic dysfunction and FW accumulation may contribute to aberrant WM microstructure and episodic memory challenges in autistic adults across a broad age range. These findings point to potential biomarkers for identifying and intervening in the cognitive aging process in autism.

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Cited bibliography overview

These indicators describe the bibliography cited by this publication. An author name is counted each time it appears in one cited reference, so the same person can be counted more than once. Names not yet linked to an author already present in AutiHub are treated as unknown, not as non-autistic. Last computed: 3 Oct 2026 01:01.

Cited references
62
With a DOI
57
Without a DOI, from raw bibliography text
5
2 / 62 (3.2%) cited references include at least one author identified as autistic.
References with data to complete
3 / 62 (4.8%)
References with detected author names
62 / 62 (100.0%)
Without detected author names
0
Without a structured title
3
Without a stable identifier
5
References with raw author names still to review
0
References with external metadata lookup issues
0
These indicators apply to cited references displayed on this page, after technical duplicates have been merged. A reference without a DOI can still support author statistics when a title and author names are available.
Author names detected in the cited bibliography
510
From DOI or external metadata
510
From validated raw bibliography text
0
Raw names already validated
0
Raw names still to review
0
63 / 510 (12.4%) names are linked to an author already present in AutiHub. 447 / 510 (87.6%) names are not yet linked.
Names linked to a person identified as autistic
2 / 510 (0.4%)
Calculated across all author names detected in the cited bibliography. Among names linked to an author already present in AutiHub: 2 / 63 (3.2%). Distinct people identified as autistic: 2 / 445 (0.4%).
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