The Use of Serum Matrix Metalloproteinases in Cerebral Amyloid Angiopathy-Related Intracerebral Hemorrhage and Cognitive Impairment

Article type: Research Article

Authors: Xia, Mingxu^{a; 1} | Su, Ya^{a; 1} | Fu, Jiayu^a | Xu, Jiajie^a | Wang, Qiong^{b; c} | Gao, Feng^c | Shen, Yong^{c; d} | Dong, Qiang^{a; *} | Cheng, Xin^{a; *}

Affiliations: [a] Department of Neurology, National Centre for Neurological Disorders, National Clinical Research Centre for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China | [b] Department of Neurology, First Affiliated Hospital of University of Science and Technology of China, Hefei, China | [c] Neurodegenerative Disorder Research Centre and Institute on Aging and Brain Disorders, University of Science and Technology of China, Hefei, China | [d] Centre for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China

Correspondence: [*] Correspondence to: Qiang Dong, MD, PhD, Department of Neurology, Huashan Hospital Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040 P. R. China. Tel.: +86 21 52887145; Fax:+86 21 52887145; E-mail: [email protected] and Xin Cheng, MD, PhD, Department of Neurology, Huashan Hospital Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040 P. R. China. Tel.: +86 21 52887145; E-mail: [email protected].

Note: [1] These authors have contributed equally to this work.

Abstract: Background:Neuroimaging has played a primary role in predicting intracerebral hemorrhage (ICH) recurrence of cerebral amyloid angiopathy (CAA); however, the utilities of biomarkers in CAA-related ICH and cognitive impairment remain unexplored. Objective:To investigate the correlations of serum levels of matrix metalloproteinase-2 (MMP-2), MMP-3, and MMP-9 with CAA-related MRI markers, ICH recurrence, and cognitive status. Methods:68 cases with first probable CAA-ICH and 69 controls were recruited. Clinical and imaging data were obtained at baseline and serum MMPs in the acute phase were measured by Luminex multiplex assays. Cognitive status was assessed with the Chinese version of Mini-Mental State Examination within 10–14 days after ICH onset. Results:Serum MMP-2 level was significantly lower in CAA-ICH patients than controls while MMP-9 was significantly higher. In CAA-ICH patients, MMP-3 level was significantly associated with lobar cerebral microbleeds count after adjusting age, sex, and hypertension (adjusted coefficient 0.368, 95%CI 0.099–0.637, p = 0.008). During a median follow-up of 2.4 years, higher level of MMP-2 predicted lower CAA-ICH recurrence after adjusting age (adjusted HR 0.326, 95%CI 0.122–0.871, p = 0.025), ICH volume (adjusted HR 0.259, 95%CI 0.094–0.715, p = 0.009), total MRI burden of SVD score (adjusted HR 0.350, 95%CI 0.131–0.936, p = 0.037) respectively. Besides, higher level of MMP-2 was significantly associated with decreased risk of cognitive impairment independent of age and ICH volume (adjusted OR 0.054, 95%CI 0.005–0.570, p = 0.015). Conclusion:Serum MMP-2 in acute phase might be a promising biomarker to predict CAA-ICH recurrence and to evaluate the risk of cognitive impairment.

Keywords: Cerebral amyloid angiopathy, cognitive impairment, cerebral microbleeds, intracerebral hemorrhage, matrix metalloproteinases

DOI: 10.3233/JAD-210288

Journal: Journal of Alzheimer's Disease, vol. 82, no. 3, pp. 1159-1170, 2021