Background: Cerebral amyloid angiopathy (CAA) is characterized by β-amyloid deposition in cortical and leptomeningeal arterioles, which might result from glymphatic dysfunction. We aimed to explore glymphatic function in CAA using the non-invasive diffusion tensor image analysis along the perivascular space (DTI-ALPS) method.


Methods: We prospectively recruited 63 patients with CAA, and 70 age- and sex-matched normal controls. We applied Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to screen global cognitive status. We conducted MRI scans to calculate the index for diffusivity along the perivascular space (ALPS-index), and linear regression models to assess its relationships with cerebral small vessel disease (CSVD) markers, cognitive status, and blood biomarkers. We applied Cox proportional hazard models to explore the role of baseline ALPS-index in disease recurrence.


Results: Patients with CAA exhibited a lower ALPS-index than controls globally (p < 0.001). Besides, the lower ALPS-index was related to more enlarged perivascular space in basal ganglia (p = 0.026), more lacunes (p < 0.001), higher white matter hyperintensities Fazekas score (p = 0.049), elevated total MRI burden of CSVD (p = 0.034), and lower MMSE (p = 0.001) as well as MoCA (p < 0.001) in CAA. During a median follow-up of 4.1 years, higher ALPS-index was associated with lower disease recurrence (p=0.022). ALPS-index was also negatively correlated with serum soluble intercellular adhesion molecule-1, neurofilament light and chitinase-3-like protein 1 in CAA.


Conclusions: Patients with CAA showed impaired glymphatic function. ALPS-index was significantly related to CSVD severity, cognitive impairment, and disease recurrence in CAA.