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Children with autism spectrum disorder and comorbid sleep disorder exhibit impaired perivascular neuroclearance linked to systemic iron deficiency.

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

Last updated: Jul 7, 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 in ASD

Limitations

  • ⚠Observational design cannot establish causality
  • ⚠Single-center study with potential selection bias
  • ⚠No direct measurement of sleep architecture (e.g., polysomnography)

Frequently Asked Questions

What is the DKI-ALPS index?▼

It is a diffusion kurtosis imaging measure along the perivascular space used to quantify neuroclearance function.

How was sleep disorder defined in this study?▼

The abstract does not specify diagnostic criteria; children were classified as ASD-SD (with sleep disorder) or ASD-nSD (without) based on clinical assessment.

What is the proposed mechanism linking iron deficiency to neuroclearance dysfunction?▼

The study suggests a pathway: iron deficiency leads to cerebral edema (increased free water fraction), which in turn impairs perivascular neuroclearance.

Could iron supplementation improve sleep in children with ASD?▼

The authors suggest targeted interventions integrating iron supplementation and sleep optimization, but this study does not test supplementation directly.

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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.