ArticleAnnals of neurology2023
Magnetic Resonance Images Implicate That Glymphatic Alterations Mediate Cognitive Dysfunction in Alzheimer Disease.
Article in Annals of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 papers, 4 of them syntheses that pooled it.
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Who cites it
157 citing papers in PubMed, 4 syntheses or guidelines pooled it, 223 citations in OpenAlex.
- Diffusion Tensor Imaging Along the Perivascular Space (DTI-ALPS) as a Neuroimaging Biomarker of Glymphatic Function in Neurodegenerative Diseases: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Glymphatic dysfunction in Alzheimer's disease: a systematic review and meta-analysis of the DTI-ALPS index as an imaging biomarker.Frontiers in aging neuroscience · 2026Pooled it
- Imaging biomarkers of glymphatic system dysfunction in Alzheimer's disease: a systematic review and meta-analysis with a focus on DTI-ALPS index.Frontiers in aging neuroscience · 2026Pooled it
- Evaluating the robustness of DTI-ALPS in clinical context: a meta-analytic parallel on Alzheimer's and Parkinson's diseases.Scientific reports · 2024Pooled it
- Effects of intermittent theta-burst stimulation on cognition and glymphatic system activity in mild cognitive impairment and very mild Alzheimer's disease: a randomized controlled trial.Journal of neuroengineering and rehabilitation · 2025Trial
- Exploring the role of glymphatic system in Alzheimer's disease with insights from MRI-based studies: a systematic review.Neuroradiology · 2026Review
- In vivo multimodal PET/MRI imaging and plasma biomarkers implicate glymphatic dysfunction linking neuroinflammation to tau pathology in the early Alzheimer's disease continuum.European journal of nuclear medicine and molecular imaging · 2026Article
- DTI-ALPS Primarily Reflects White Matter Diffusion Dispersion and Microstructural Heterogeneity in Neurodegeneration: Insights From Multi-Modal MRI.Human brain mapping · 2026Article
- High frame ratebioRxiv : the preprint server for biology · 2026Article
- The role of glymphatic-related structural and functional imaging biomarkers in the pathological progression of Alzheimer's disease: a multimodal imaging-based study.Quantitative imaging in medicine and surgery · 2026Article
- Serial failure of the brain clearance continuum in Alzheimer's disease: mechanisms and therapeutic perspectives.Journal of neurology · 2026Review
- Peripheral inflammation impairs glymphatic function, contributing to neurodegeneration in Alzheimer's disease.iScience · 2026Article
- The glymphatic system in sleep: a nexus of waste clearance, brain homeostasis, and disease intervention.Molecular psychiatry · 2026Review
- Glymphatic dysfunction associates with regional white matter hyperintensities and plasma amyloid-β burden across the Alzheimer's disease continuum.Psychological medicine · 2026Article
- Associations between altered morphometric inverse divergence networks, choroid plexus volume, and perivascular space network in patients with Parkinson disease: a cross-sectional study.Quantitative imaging in medicine and surgery · 2026Article
- DTI-ALPS and subcortical structural-functional coupling mediate the impact of sleep quality on working memory in insomnia disorder.Psychological medicine · 2026Article
- Hierarchical organization of tau topography across the Alzheimer's disease continuum integrates amyloid, connectome, and intrinsic molecular vulnerability.Communications biology · 2026Article
- Glymphatic dysfunction is associated with cognitive impairment in white matter hyperintensities: A DTI-based study.IBRO neuroscience reports · 2026Article
- Putative glymphatic dysfunction links extracellular fluid dysregulation to white matter degeneration and clinical impairment in amyotrophic lateral sclerosis.BMC medicine · 2026Article
- A clinically feasible framework to estimate tau pathology and clinical-biological discordance in the Alzheimer's disease spectrum.Alzheimer's research & therapy · 2026Article
97 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe glymphatic system cleans amyloid and tau proteins from the brain in animal studies of Alzheimer disease (AD). However, there is no direct evidence showing this in humans.
methodsParticipants (n = 50, 62.6 ± 5.4 years old, 36 women) with AD and normal controls underwent amyloid positron emission tomography (PET), tau PET, structural T1-weighted magnetic resonance imaging, and neuropsychological evaluation. Whole-brain glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS).
resultsALPS-indexes showed negative correlations with deposition of amyloid and tau on PET images and positive correlations with cognitive scores even after adjusting for age, sex, years of education, and APOE4 genotype covariates in multiple AD-related brain regions (all p < 0.05). Mediation analysis showed that ALPS-index acted as a significant mediator between regional standardized uptake value ratios of amyloid and tau images and cognitive dysfunction even after correcting for multiple covariates in AD-related brain regions. These regions are responsible for attention, memory, and executive function, which are vulnerable to sleep deprivation.
interpretationGlymphatic system activity may act as a significant mediator in AD-related cognitive dysfunction even after adjusting for multiple covariates and gray matter volumes. ALPS-index may provide useful disease progression or treatment biomarkers for patients with AD as an indicator of modulation of glymphatic activity. ANN NEUROL 2023;93:164-174.
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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.