{"doi":"10.1016/j.tjpad.2025.100228","title":"The coupling of global brain activity and cerebrospinal fluid flow as a potential predictive marker of brain amyloid-β accumulation","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.","journal":"The Journal of Prevention of Alzheimer s Disease","year":2025,"id":514334,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9622,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":553942,"name":"Koji Kamagata","orcid":"0000-0001-5028-218X","position":1,"is_corresponding":false},{"id":553943,"name":"Yuya Saito","orcid":"0000-0002-4033-1424","position":2,"is_corresponding":false},{"id":839816,"name":"Kaito Takabayashi","orcid":"0000-0002-5562-1504","position":3,"is_corresponding":false},{"id":1377534,"name":"Rinako Iseki","orcid":null,"position":4,"is_corresponding":false},{"id":1376916,"name":"Wataru Uchida","orcid":"0000-0002-8453-1532","position":5,"is_corresponding":false},{"id":553945,"name":"Christina Andica","orcid":"0000-0002-9339-6950","position":6,"is_corresponding":false},{"id":409637,"name":"Akifumi Hagiwara","orcid":"0000-0001-5277-3249","position":7,"is_corresponding":false},{"id":28726,"name":"Akihiko Wada","orcid":"0000-0003-3432-0267","position":8,"is_corresponding":false},{"id":28729,"name":"Toshiaki Akashi","orcid":"0000-0002-3056-0792","position":9,"is_corresponding":false},{"id":690559,"name":"Osamu Abe","orcid":"0000-0002-1180-2629","position":10,"is_corresponding":false},{"id":28738,"name":"Shigeki Aoki","orcid":"0000-0002-8491-0698","position":11,"is_corresponding":false},{"id":1066745,"name":"Yuya Tanaka","orcid":"0000-0003-0260-0424","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T02:48:29.165853Z","pmid":"40517084","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}