Diffusion Tensor Imaging along the Perivascular Space for Characterizing Cerebral Interstitial Fluid Dynamics in Alzheimer Disease: A Systematic Review and Meta-Analysis.
| Publication Type | Review |
| Authors | Khalafi M, Shirbandi K, Zhou L, Butler T, Chen K, Dartora W, Keil S, Li Y, Chiang G |
| Journal | AJNR Am J Neuroradiol |
| Volume | 47 |
| Issue | 2 |
| Pagination | 401-408 |
| Date Published | 02/03/2026 |
| ISSN | 1936-959X |
| Keywords | Alzheimer Disease, Glymphatic System, Extracellular Fluid, Diffusion Tensor Imaging |
| Abstract | BACKGROUND: DTI along the perivascular space (ALPS) has emerged as a measure of cerebral interstitial fluid dynamics, a proposed component of the glymphatic system, which may provide insight into central nervous system fluid transport and waste clearance. PURPOSE: Our study aimed to evaluate whether DTI-ALPS can serve as a reliable, noninvasive imaging biomarker of altered interstitial fluid dynamics across the Alzheimer disease (AD) continuum. DATA SOURCES: We searched Scopus, Web of Science, and PubMed for articles published through October 2024. STUDY SELECTION: Studies were included if they reported the ALPS index in AD, mild cognitive impairment (MCI), and healthy control (HC) groups. Studies were excluded if they lacked sufficient data or involved overlapping cohorts. DATA ANALYSIS: Using standardized mean difference (SMD), we compared the ALPS index in AD and MCI groups to HCs. We assessed the association between the ALPS index and cognitive function by using a random-effects model. A qualitative risk bias assessment was conducted by using the Newcastle-Ottawa Scale (NOS). DATA SYNTHESIS: Nineteen studies met the inclusion criteria. The overall ALPS index was significantly lower in AD subjects than in HCs (SMD = -1.07; 95% CI: -1.57 to -0.56). Statistically significant differences were also observed between AD and MCI subjects (SMD = -0.25; 95% CI: -0.40 to -0.10), as well as between MCI and HC subjects (SMD = -0.81; 95% CI: -1.57 to -0.06). Additionally, the ALPS index showed a statistically significant association with Mini-Mental State Examination scores (pooled correlation effect size =0.43; 95% CI: 0.28 to 0.57). A negative correlation was also observed between the ALPS index and amyloid deposition on PET, with a pooled correlation effect size of -0.42 (95% CI: -0.66 to -0.19, P < .001). LIMITATIONS: Potential limitations include heterogeneity across imaging protocols, variability in cognitive assessments, and possible publication bias. CONCLUSIONS: The DTI-ALPS technique showed significant differences among cognitive groups across the AD continuum and was associated with cognitive scores and brain amyloidosis. This provides further evidence that DTI-ALPS could be useful in detecting altered cerebral interstitial fluid dynamics in MCI and AD. |
| DOI | 10.3174/ajnr.A8953 |
| PubMed ID | 40759558 |
| PubMed Central ID | PMC12867041 |