全脑活动与脑脊液流动的耦合作为脑淀粉样蛋白-β积累的潜在预测标志物。

The coupling of global brain activity and cerebrospinal fluid flow as a potential predictive marker of brain amyloid-β accumulation.

作者信息

Tanaka Yuya, Kamagata Koji, Saito Yuya, Takabayashi Kaito, Iseki Rinako, Uchida Wataru, Andica Christina, Hagiwara Akifumi, Wada Akihiko, Akashi Toshiaki, Abe Osamu, Aoki Shigeki

机构信息

Department of Radiology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan; Department of Radiology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.

Department of Radiology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan.

出版信息

J Prev Alzheimers Dis. 2025 Sep;12(8):100228. doi: 10.1016/j.tjpad.2025.100228. Epub 2025 Jun 13.

DOI:10.1016/j.tjpad.2025.100228

PMID:40517084

Abstract

BACKGROUND

Impaired cerebrospinal fluid (CSF) clearance is thought to contribute to amyloid-β (Aβ) accumulation in Alzheimer's disease (AD). Global brain activity-CSF flow coupling (gBOLD-CSF coupling), measured through resting-state functional MRI, reflects CSF clearance capacity. A higher coupling value indicates weaker coupling. Its potential as a predictive marker for Aβ accumulation remains unclear.

OBJECTIVES

This study aims to determine whether weaker gBOLD-CSF coupling precedes Aβ accumulation in cognitively normal, Aβ-negative individuals and to explore its predictive potential for amyloid conversion.

DESIGN

A longitudinal observational study using Alzheimer's Disease Neuroimaging Initiative (ADNI) data.

SETTING

Data from ADNI-participating sites.

PARTICIPANTS

16 cognitively normal participants, initially Aβ-negative: seven fast-converters (transitioned to Aβ-positive within two years) and nine slow-converters (remained Aβ-negative for at least two years).

MEASUREMENTS

gBOLD-CSF coupling was calculated as the Pearson correlation coefficient between global Blood-Oxygen-Level-Dependent (BOLD) and CSF inflow signals. Group differences in gBOLD-CSF coupling were analyzed, along with partial correlation analyses between gBOLD-CSF coupling and annual changes in Aβ biomarkers and cognitive scores.

RESULTS

Fast-converters showed significantly higher gBOLD-CSF coupling values, indicating weaker coupling (Cohen's d = 1.76, p = 0.012). Coupling values positively correlated with annual changes in Aβ-PET SUVR (r = 0.594, p = 0.054) and negatively with MoCA scores (r = -0.654, p = 0.021).

CONCLUSION

Weaker gBOLD-CSF coupling precedes brain Aβ accumulation, indicating its potential as a predictive marker for amyloid conversion. Future studies should refine clinical thresholds for early intervention strategies in AD prevention.

摘要

背景

脑脊液（CSF）清除功能受损被认为与阿尔茨海默病（AD）中β淀粉样蛋白（Aβ）的积累有关。通过静息态功能磁共振成像测量的全脑活动 - CSF 流动耦合（gBOLD - CSF 耦合）反映了 CSF 清除能力。较高的耦合值表明耦合较弱。其作为 Aβ 积累预测标志物的潜力尚不清楚。

目的

本研究旨在确定在认知正常、Aβ 阴性个体中，较弱的 gBOLD - CSF 耦合是否先于 Aβ 积累，并探讨其对淀粉样蛋白转化的预测潜力。

设计

一项使用阿尔茨海默病神经影像倡议（ADNI）数据的纵向观察性研究。

设置

来自 ADNI 参与站点的数据。

参与者

16 名认知正常参与者，最初为 Aβ 阴性：7 名快速转化者（在两年内转变为 Aβ 阳性）和 9 名缓慢转化者（至少两年保持 Aβ 阴性）。

测量

gBOLD - CSF 耦合计算为全脑血氧水平依赖（BOLD）信号与 CSF 流入信号之间的 Pearson 相关系数。分析了 gBOLD - CSF 耦合的组间差异，以及 gBOLD - CSF 耦合与 Aβ 生物标志物年度变化和认知评分之间的偏相关分析。

结果

快速转化者显示出显著更高的 gBOLD - CSF 耦合值，表明耦合较弱（Cohen's d = 1.76，p = ０.０１２）。耦合值与 Aβ - PET SUVR 的年度变化呈正相关（r = 0.594，p = 0.0５４），与 MoCA 评分呈负相关（r = -0.654，p = 0.0２１）。