A Novel Diffusion Tensor Image Analysis Along the Perivascular Space Method to Evaluate Glymphatic Alterations in Alzheimer’s Disease

Alzheimer 's disease (AD) is the most prevalent neurodegenerative disorder worldwide. The glymphatic system is considered to be associated with the pathogenesis of AD. However, the alterations of glymphatic system along the AD continuum are still unknown. In this study, we used a novel DTI analysis method, diffusion tensor image analysis along the perivascular space (DTI-ALPS), to evaluate the difference in the activity of the glymphatic system among normal control (NC) subjects, mild cognitive impairment (MCI) and AD patients. The data utilized in the study was obtained from Tongji Hospital in Shanghai, China, including 65 NCs, 58 MCIs and 36 ADs. First, we calculated the ALPS-index to evaluate the activity of the glymphatic system. Then, analysis of variance (ANOVA) was used to find the differences of ALPS-index among different groups, and to explore the correlation between ALPS-index and the three clinical scales: Minimum Mental State Examination (MMSE), Montreal Cognitive Assessment-Basic (MoCA-B) and Instrumental Activity of Daily Living (IADL). Receiver operating characteristic curve (ROC) analysis was used to evaluate the role of the ALPS-index in disease classification. The findings indicated a significant difference in the ALPS-index between the groups of participants with normal cognition, MCI, and AD. In addition, we found that ALPS-index was significantly correlated with the scores of the three clinical scales (with MoCA-B: r=0.233, p=0.001). Furthermore, with ALPS-index, Fractional Anisotropy (FA) values achieved best classification results (AUC=0.8899). Cognitive dysfunction is closely associated with the activity of the glymphatic system, and ALPS-index can be used as a biomarker for alterations along the AD continuum.