Diffusion Tensor Imaging Along the Perivascular Space for Characterizing Cerebral Interstitial Fluid Dynamics in Alzheimer's Disease: A Systematic Review and Meta-Analysis

Abstract

Background: Diffusion Tensor Imaging along the Perivascular Space (DTI-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's 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 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 healthy controls. We assessed the association between the ALPS index and cognitive function using a random-effects model. A qualitative risk bias assessment was conducted 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 healthy controls (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 healthy control 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 < 0.001).

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.

Abbreviations: AD＝ Alzheimer's disease; Aβ＝ beta-amyloid; PET＝ positron emission tomography; PiB＝ Pittsburgh Compound B; FBB＝ Florbetaben; CL＝ Centiloid.