Glymphatic dysfunction correlates with severity of small vessel disease and cognitive impairment in cerebral amyloid angiopathy

Jiajie Xu; Ya Su; Jiayu Fu; Xiaoxiao Wang; Benedictor Alexander Nguchu; Bensheng Qiu; Qiang Dong; Xin Cheng

doi:10.1111/ene.15450

Glymphatic dysfunction correlates with severity of small vessel disease and cognitive impairment in cerebral amyloid angiopathy

Eur J Neurol. 2022 Oct;29(10):2895-2904. doi: 10.1111/ene.15450. Epub 2022 Jul 3.

Authors

Jiajie Xu¹, Ya Su¹, Jiayu Fu¹, Xiaoxiao Wang², Benedictor Alexander Nguchu², Bensheng Qiu², Qiang Dong^{1

3}, Xin Cheng¹

Affiliations

¹ Department of Neurology, National Center for Neurological Disorders, National Clinical Research Centre for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
² Hefei National Lab for Physical Sciences at the Microscale and the Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, China.
³ State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.

PMID: 35712978
DOI: 10.1111/ene.15450

Abstract

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

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

Results: Patients with CAA exhibited a lower ALPS index than controls globally (p < 0.001). In addition, a lower ALPS index was related to more enlarged perivascular space in basal ganglia (p = 0.026), more lacunes (p < 0.001), higher white matter hyperintensity Fazekas score (p = 0.049), elevated total magnetic resonance imaging burden of CSVD (p = 0.034) and lower Mini-Mental State Examination (p = 0.001) as well as Montreal Cognitive Assessment (p < 0.001) in CAA. During a median follow-up of 4.1 years, a higher ALPS index was associated with lower disease recurrence (p = 0.022). The 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. The ALPS index was significantly related to CSVD severity, cognitive impairment and disease recurrence in CAA.

Keywords: cerebral amyloid angiopathy; cerebral small vessel disease neuroimaging markers; cognitive function; diffusion tensor imaging; glymphatic system.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Cerebral Amyloid Angiopathy* / complications
Cerebral Amyloid Angiopathy* / diagnostic imaging
Cerebral Small Vessel Diseases* / complications
Cerebral Small Vessel Diseases* / diagnostic imaging
Cognitive Dysfunction* / complications
Cognitive Dysfunction* / etiology
Humans
Image Processing, Computer-Assisted
Magnetic Resonance Imaging / methods

Substances

Biomarkers