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

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. 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. We searched Scopus, Web of Science, and PubMed for articles published through October 2024. 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. 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). 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). Potential limitations include heterogeneity across imaging protocols, variability in cognitive assessments, and possible publication bias. 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. AD＝ Alzheimer's disease; Aβ＝ beta-amyloid; PET＝ positron emission tomography; PiB＝ Pittsburgh Compound B; FBB＝ Florbetaben; CL＝ Centiloid.