ArticleEuropean journal of nuclear medicine and molecular imaging2025
DTI-ALPS index-assessed glymphatic dysfunction mediates Alzheimer's cognitive decline via amyloid-β-dependent pathways: multimodal PET/MRI study.
Article in European journal of nuclear medicine and molecular imaging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.
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Who cites it
12 citing papers in PubMed, 2 syntheses or guidelines pooled 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
- 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
- DTI-ALPS as a Biomarker of Small Vessel Disease Progression and Amyloid-β in Normal Aging: A 3-Year Longitudinal Study.Human brain mapping · 2026Article
- The Clearance-Centered Bottleneck in Alzheimer's Disease: From Coupled Glymphatic-Lymphatic Circuits to Therapeutic Opportunities.Molecular neurobiology · 2026Review
- Glymphatic dysfunction is associated with hyperglycemia-related cortical thinning in patients with type 2 diabetes mellitus.Journal of endocrinological investigation · 2026Article
- Glymphatic system impairment in neurological disorders: potential mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Association between MRI indicators of the glymphatic system and cognition in high-risk populations for Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2026Article
- Early detection of Alzheimer's disease via multimodal MRI and machine learning.Frontiers in aging neuroscience · 2026Article
- Tissue-specific diffusion abnormalities and localized free-water reductions in hypertension despite no detectable group difference in the DTI-ALPS index.Frontiers in medicine · 2026Article
- Pathophysiologic similarities between autism spectrum disorder and Alzheimer's disease: therapeutic possibilities.Frontiers in neuroscience · 2025Article
- Research progress in neuroimaging of sporadic early-onset Alzheimer's disease.Frontiers in neurologyReview
- Diffusion tensor imaging along the perivascular space and choroid plexus volume for assessing the brain glymphatic system in overt hypothyroidism.Frontiers in neurologyArticle
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
purposeThe role of glymphatic dysfunction in Alzheimer's disease (AD), as measured by diffusion tensor imaging along perivascular spaces (DTI-ALPS) indexing of perivascular function, its progression, and its interaction with amyloid-β (Aβ) and tau proteins, remains controversial. To investigate whether the DTI-ALPS index mediates AD-related cognitive decline through Aβ/tau-dependent pathways using tri-tracer PET/MRI.
methodsThis retrospective study (2021-2024) analyzed 140 participants (median age 69.00 [61.00, 74.00] years; 84 women), including 99 with AD (37 early-onset [EOAD], 62 late-onset [LOAD]), 35 with mild cognitive impairment (MCI), and 6 with subjective cognitive decline (SCD). All participants underwent simultaneous [
resultsThe ALPS index progressively decreased across clinical stages (SCD: 1.51 ± 0.08 vs. MCI: 1.37 ± 0.13 vs. AD: 1.32 ± 0.14; P = 0.001), correlating with higher Aβ-PET (r = - 0.31, P < 0.001), tau-PET (ρ = - 0.18, P = 0.035), and FDG-PET scores (ρ = - 0.22, P = 0.008). Aβ-PET fully mediated the ALPS effects on FDG-PET (β = - 0.14, P = 0.002) and cognition (β = 0.12 ~ 0.14, P < 0.01), independent of tau (P > 0.05). The Aβ-negative subgroups showed correlations with ALPS-age (r = - 0.48, P = 0.007), ALPS-education (r = 0.39, P = 0.035), and ALPS-cognition (MoCA: r = 0.62, P < 0.001). The Aβ-positive subgroups revealed inverse ALPS-Aβ associations (ρ = - 0.27, P = 0.010; age/education-adjusted ρ = - 0.24, P = 0.022) alongside positive adjusted correlations with cognition (MMSE: ρ = 0.28, P = 0.009). EOAD exhibited distinct ALPS-cognition relationships compared to LOAD (MMSE: r = - 0.39, P = 0.016 vs. ρ = - 0.06, P = 0.620).
conclusionDTI-ALPS quantifies glymphatic dysfunction driving AD progression predominantly through Aβ-dependent pathways, with EOAD demonstrating distinct neuroimaging-cognition relationships compared to LOAD.
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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 Socratic graph.