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Children with autism and sleep disorder exhibit impaired neuroclearance linked to systemic iron deficiency

In a study of 230 children with ASD (114 with sleep disorder, ASD-SD; 116 without, ASD-nSD) and 110 typically developing controls, ASD-SD children showed significantly reduced ALPS indices and elevated free water fraction, indicating impaired perivascular clearance. Serum iron was markedly lower in ASD-SD, and mediation analysis supported a pathway from iron deficiency to cerebral edema to impaired neuroclearance.

Last updated: Aug 26, 2026•0 RCTs•📖 Read as article →

Evidence Score

Evidence Score34/100
Human RCT☆☆☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. Neuroclearance dysfunction in autism with sleep disorder: MRI evidence and mediation by systemic iron deficiency.

observational

Yin BY, Deng YY, Chen X, Zhao JY, Ni YX, Zhong SS, Zou FY, Shen LS, Luo XW, Zhou X, Zhang JL, Zhou WY, Deng HZ, Guo RM · Journal of affective disorders (2026)

Participants: N/A
Duration: N/A (cross-sectional)
Intervention: None (observational study comparing groups with and without sleep disorder)
Outcome: Neuroclearance function (DKI-ALPS index, free water fraction, perivascular space volume fraction) and serum iron levels
Effect Size: AUC up to 0.94 for combined ALPS and serum Fe distinguishing ASD-SD from ASD-nSD and controls
Population: Children with autism spectrum disorder (ASD) aged 2-17 years, with and without comorbid sleep disorder, plus typically developing controls

Result:

PubMed: 42208817DOI: 10.1016/j.jad.2026.122035

Mechanism Graph

Systemic iron deficiency
↓
Increased cerebral edema (elevated free water fraction)
↓
Impaired perivascular neuroclearance (reduced ALPS index)
↓
Sleep disruption exacerbates neurodevelopmental impairments

Limitations

  • ⚠Cross-sectional design prevents causal inference
  • ⚠Single-center study may limit generalizability
  • ⚠Sleep disorder diagnosis based on clinical criteria, not objective polysomnography

Frequently Asked Questions

What is the ALPS index?▼

The ALPS index (diffusion kurtosis imaging along the perivascular space) is an MRI measure of perivascular clearance function, reflecting the brain's ability to clear waste products via the glymphatic system.

How does iron deficiency relate to sleep in autism?▼

The study found that children with ASD and sleep disorder had significantly lower serum iron levels, and mediation analysis suggested iron deficiency contributes to impaired neuroclearance by increasing cerebral edema.

Can iron supplementation help sleep in autistic children?▼

The authors suggest that iron supplementation combined with sleep optimization may be a targeted intervention, but the study does not test this directly; further clinical trials are needed.

What was the sample size and composition?▼

The study included 230 children with ASD (114 with sleep disorder, 116 without) and 110 typically developing controls, totaling 340 participants.

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References

  1. 1.Yin BY, Deng YY, Chen X, Zhao JY, Ni YX, Zhong SS, Zou FY, Shen LS, Luo XW, Zhou X, Zhang JL, Zhou WY, Deng HZ, Guo RM. "Neuroclearance dysfunction in autism with sleep disorder: MRI evidence and mediation by systemic iron deficiency.." Journal of affective disorders, 2026. PMID: 42208817 DOI: 10.1016/j.jad.2026.122035
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.