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Objectives <p>White matter (WM) blood oxygenation level-dependent (BOLD) signals show abnormalities in Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI). However, the changes of WM static amplitude of low‑frequency fluctuation (sALFF) and dynamic amplitude of low‑frequency fluctuation (dALFF) as well as the WM seed-based functional connectivity (SBFC) remain to be further investigated.</p> Methods <p>We compared WM sALFF, dALFF, and SBFC across 48 AD patients, 38 aMCI patients, and 38 healthy controls (HCs), with four covariates regressed out: age, gender, educational level, and head motion parameters (mean framewise displacement). The correlation between sALFF and dALFF values and cognitive performance in AD and aMCI groups was analyzed separately after regressing out the same four covariates, with FDR correction.</p> Results <p>In AD and aMCI patients, the brain regions where WM sALFF and dALFF were abnormal in the right anterior thalamic radiation (ATR) and left ATR, respectively (sALFF: <i>F</i> = 10.171, <i>P</i> &lt; 0.001; dALFF: <i>F</i> = 10.058, <i>P</i> &lt; 0.001). In the right ATR-based functional connectivity (FC), the left putamen and right superior occipital gyrus showed abnormalities, while in the left ATR-based FC, the left middle frontal gyrus showed abnormality (left putamen: <i>F</i> = 10.201, <i>P</i> &lt; 0.001; right superior occipital gyrus: <i>F</i> = 10.970, <i>P</i> &lt; 0.001; left middle frontal gyrus: <i>F</i> = 10.933, <i>P</i> &lt; 0.001). In addition, there was a significant negative correlation between sALFF value of right ATR and dALFF value of left ATR and overall cognitive performance (Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)).</p> Conclusion <p>This study provides novel neuroimaging evidence for AD pathogenesis and a broader biomarker of cognitive vulnerability or white matter functional dysregulation.</p>

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Brain white matter functional alterations in patients with Alzheimer’s disease and amnestic mild cognitive impairment

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月5日

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  • Yi Lin,
  • Fengyi Dai,
  • Diewen Dong,
  • Yifan Jia,
  • Junqin Zhang,
  • Yan Chen,
  • Xiuhong Ge,
  • Zhongxiang Ding,
  • Luoyu Wang,
  • Qi Feng

摘要

Objectives

White matter (WM) blood oxygenation level-dependent (BOLD) signals show abnormalities in Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI). However, the changes of WM static amplitude of low‑frequency fluctuation (sALFF) and dynamic amplitude of low‑frequency fluctuation (dALFF) as well as the WM seed-based functional connectivity (SBFC) remain to be further investigated.

Methods

We compared WM sALFF, dALFF, and SBFC across 48 AD patients, 38 aMCI patients, and 38 healthy controls (HCs), with four covariates regressed out: age, gender, educational level, and head motion parameters (mean framewise displacement). The correlation between sALFF and dALFF values and cognitive performance in AD and aMCI groups was analyzed separately after regressing out the same four covariates, with FDR correction.

Results

In AD and aMCI patients, the brain regions where WM sALFF and dALFF were abnormal in the right anterior thalamic radiation (ATR) and left ATR, respectively (sALFF: F = 10.171, P < 0.001; dALFF: F = 10.058, P < 0.001). In the right ATR-based functional connectivity (FC), the left putamen and right superior occipital gyrus showed abnormalities, while in the left ATR-based FC, the left middle frontal gyrus showed abnormality (left putamen: F = 10.201, P < 0.001; right superior occipital gyrus: F = 10.970, P < 0.001; left middle frontal gyrus: F = 10.933, P < 0.001). In addition, there was a significant negative correlation between sALFF value of right ATR and dALFF value of left ATR and overall cognitive performance (Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)).

Conclusion

This study provides novel neuroimaging evidence for AD pathogenesis and a broader biomarker of cognitive vulnerability or white matter functional dysregulation.