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Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413707 | PMC |
| http://dx.doi.org/10.1016/j.tjpad.2025.100228 | DOI Listing |
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