journal articles
THE COUPLING OF GLOBAL BRAIN ACTIVITY AND CEREBROSPINAL FLUID FLOW AS A POTENTIAL PREDICTIVE MARKER OF BRAIN AMYLOID-Β ACCUMULATION
Yuya Tanaka, Koji Kamagata, Yuya Saito, Kaito Takabayashi, Rinako Iseki, Wataru Uchida, Christina Andica, Akifumi Hagiwara, Akihiko Wada, Toshiaki Akashi, Osamu Abe, Shigeki Aoki, Alzheimer’s Disease Neuroimaging Initiative
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.
CITATION:
Yuya Tanaka ; Koji Kamagata ; Yuya Saito ; Kaito Takabayashi ; Rinako Iseki ; Wataru Uchida ; Christina Andica ; Akifumi Hagiwara ; Akihiko Wada ; Toshiaki Akashi ; Osamu Abe ; Shigeki Aoki ; Alzheimer’s Disease Neuroimaging Initiative (2025): The coupling of global brain activity and cerebrospinal fluid flow as a potential predictive marker of brain amyloid-β accumulation. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.100228