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Background <p>Neurocognitive decline is common after brain radiotherapy (RT), but underlying mechanisms remain unclear. Altered glymphatic flow has been implicated in cognitive impairment in other neurologic conditions. Diffusion Tensor Imaging (DTI) Analysis along the Perivascular Space (ALPS)-index is a candidate biomarker of glymphatic function. We evaluated changes in ALPS-index and neurocognition following whole brain radiation therapy (WBRT) and partial brain radiation therapy (PBRT).</p> Methods <p>A prospective, single-arm study was conducted in patients receiving fractionated brain RT from 2015 to 2019. Patients had comprehensive brain imaging and formal neurocognitive testing (Trails B z-score) at baseline and follow-up. Due to the limited sample size, associations between baseline characteristics, ALPS-index, and Trails B z-score were summarized descriptively.</p> Results <p>Of 15 enrolled patients, 7 had suitable diffusion imaging for ALPS-index analysis. Four patients received WBRT (23.4–35&#xa0;Gy/13–14 fractions) and three received PBRT (30–39&#xa0;Gy/10–13 fractions). At 2 months, ALPS-index declined after WBRT (median − 4.0%, range − 18.6% to -0.6%) and increased after PBRT (median + 3.3%, range 0.0% to + 5.0%). Greater ALPS-index change was observed with lower KPS and multiple metastases. Median Trails B z-score decreased by -3.35 after WBRT versus − 0.15 after PBRT. Among patients with 24-month follow-up, ALPS-indices increased by median 2.2% after WBRT and declined by 0.4% after PBRT; Trails B z-score declined by 1.40 after WBRT and improved by 0.61 after PBRT.</p> Conclusions <p>Early decrease in ALPS-index and worse neurocognitive change is observed after WBRT as compared to PBRT. The contribution of ALPS-index and glymphatic dysfunction to cognitive changes after brain RT merit further investigation.</p>

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Longitudinal changes of neurocognitive function and ALPS-index in patients with brain tumors receiving brain irradiation

  • 期刊论文

  • 发表日期：

    2026年3月12日

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  • Anurag Saraf,
  • Jeremy Ford,
  • Michael Parsons,
  • Janet Sherman,
  • Nora K. Horick,
  • Beow Y. Yeap,
  • Irene Wang,
  • Jorg Dietrich,
  • Helen A. Shih

摘要

Background

Neurocognitive decline is common after brain radiotherapy (RT), but underlying mechanisms remain unclear. Altered glymphatic flow has been implicated in cognitive impairment in other neurologic conditions. Diffusion Tensor Imaging (DTI) Analysis along the Perivascular Space (ALPS)-index is a candidate biomarker of glymphatic function. We evaluated changes in ALPS-index and neurocognition following whole brain radiation therapy (WBRT) and partial brain radiation therapy (PBRT).

Methods

A prospective, single-arm study was conducted in patients receiving fractionated brain RT from 2015 to 2019. Patients had comprehensive brain imaging and formal neurocognitive testing (Trails B z-score) at baseline and follow-up. Due to the limited sample size, associations between baseline characteristics, ALPS-index, and Trails B z-score were summarized descriptively.

Results

Of 15 enrolled patients, 7 had suitable diffusion imaging for ALPS-index analysis. Four patients received WBRT (23.4–35 Gy/13–14 fractions) and three received PBRT (30–39 Gy/10–13 fractions). At 2 months, ALPS-index declined after WBRT (median − 4.0%, range − 18.6% to -0.6%) and increased after PBRT (median + 3.3%, range 0.0% to + 5.0%). Greater ALPS-index change was observed with lower KPS and multiple metastases. Median Trails B z-score decreased by -3.35 after WBRT versus − 0.15 after PBRT. Among patients with 24-month follow-up, ALPS-indices increased by median 2.2% after WBRT and declined by 0.4% after PBRT; Trails B z-score declined by 1.40 after WBRT and improved by 0.61 after PBRT.

Conclusions

Early decrease in ALPS-index and worse neurocognitive change is observed after WBRT as compared to PBRT. The contribution of ALPS-index and glymphatic dysfunction to cognitive changes after brain RT merit further investigation.