ArticlePLoS biology2021
Reduced coupling between cerebrospinal fluid flow and global brain activity is linked to Alzheimer disease-related pathology.
Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 91 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Simultaneous EEG-fMRI Study in Healthy Humans During Induction of Propofol Anesthesia to Investigate the Dynamics of Thalamocortical Functional Connectivity in the Alpha Frequency
Investigating the Link Between Preoperative Glymphatic Transport and Postoperative Delirium
Who cites it
91 citing papers in PubMed, 2 syntheses or guidelines pooled it, 134 citations in OpenAlex.
- A systematic review of global signal topography in aging, neuropsychiatric disorders, and cognitive task performance.Brain imaging and behavior · 2026Pooled it
- Glymphatic Pathway Dysfunction in Mild Cognitive Impairment: A Systematic Review and Meta-Analysis Using Diffusion Tensor Imaging Along the Perivascular Space.CNS neuroscience & therapeutics · 2025Pooled it
- Exploring the role of glymphatic system in Alzheimer's disease with insights from MRI-based studies: a systematic review.Neuroradiology · 2026Review
- The Role of Glymphatic Clearance in Affective Decision-Making in Adolescents with Non-Suicidal Self-Injury.CNS neuroscience & therapeutics · 2026Article
- Quantifying Cardiac, Respiratory, and Low Frequency Components of CSF Motion From fMRI Inflow Effects.Magnetic resonance in medicine · 2026Article
- Altered Neurofluid Dynamics Markers in Middle-Aged and Older Women With Insomnia: A Multiparametric MR Neuroimaging Study.Journal of magnetic resonance imaging : JMRI · 2026Article
- Global brain activity links subcortical degeneration to cortical tau progressively across Braak regions over early Alzheimer's disease stages.Nature communications · 2026Article
- Multimodal MRI reveals glymphatic system activity associated with systemic inflammation and neuropsychiatric symptoms in Crohn's disease.Journal of gastroenterology · 2026Article
- Task-Evoked Functional Activation and Coupling With CSF Flow Detected in the Human Brain With Ultrashort Echo Time fMRI at 7 T.NMR in biomedicine · 2026Article
- Cholinergic basal forebrain modulation of glymphatic function: implications for depression.Translational psychiatry · 2026Article
- Pupil size is linked to opposite signal fluctuations between cortical BOLD and ventricular CSF.NeuroImage · 2026Article
- Periventricular diffusivity at the ventricular-parenchymal interface across healthy controls, episodic migraine, and chronic migraine: a cross-sectional multimodal MRI study.The journal of headache and pain · 2026Article
- Greater hypoxic burden predicts weaker coordination between brain pulsation and CSF flow on 7T MRI independent of non-hypoxic arousals: Implications for glymphatic activity.bioRxiv : the preprint server for biology · 2026Article
- Impaired glymphatic function and advanced brain age gap in chronic migraine: a multimodal MRI study.The journal of headache and pain · 2026Article
- DTI-ALPS Is Associated with Temporolimbic Amyloid but Not Plasma p-Tau181 Across the Alzheimer's Disease Continuum.Research square · 2026Article
- Reduced Coupling of Global Brain Activity and Cerebrospinal Fluid Flow in Individuals With Betel Quid Dependence.Addiction biology · 2026Article
- Myasthenia Gravis patients have reduced DTI-ALPS-Index and gBOLD-CSF coupling, suggesting impaired brain waste clearance.Brain imaging and behavior · 2026Article
- Within- and between-person associations of sleep characteristics with daily cognitive performance in a community-based sample of older adults.Sleep health · 2026Article
- Sleep deprivation exhibits an age-dependent effect on infraslow global brain activity.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Coupling between global brain blood oxygen level-dependent activity and cerebrospinal fluid dynamics in young endurance athletes.Experimental physiology · 2026Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The glymphatic system plays an important role in clearing the amyloid-β (Aβ) and tau proteins that are closely linked to Alzheimer disease (AD) pathology. Glymphatic clearance, as well as Aβ accumulation, is highly dependent on sleep, but the sleep-dependent driving forces behind cerebrospinal fluid (CSF) movements essential to the glymphatic flux remain largely unclear. Recent studies have reported that widespread, high-amplitude spontaneous brain activations in the drowsy state and during sleep, which are shown as large global signal peaks in resting-state functional magnetic resonance imaging (rsfMRI), are coupled with CSF movements, suggesting their potential link to glymphatic flux and metabolite clearance. By analyzing multimodal data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) project, here we showed that the coupling between the global fMRI signal and CSF influx is correlated with AD-related pathology, including various risk factors for AD, the severity of AD-related diseases, the cortical Aβ level, and cognitive decline over a 2-year follow-up. These results provide critical initial evidence for involvement of sleep-dependent global brain activity, as well as the associated physiological modulations, in the clearance of AD-related brain waste.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.