Mixed-Location Cerebral Microbleeds: An Imaging Biomarker for Cerebrovascular Pathology in Cognitive Impairment and Dementia in a Memory Clinic Population

Article type: Research Article

Authors: Gyanwali, Bibek^{a; c; 1} | Shaik, Muhammad Amin^{b; 1} | Venketasubramanian, Narayanaswamy^d | Chen, Christopher^{a; c} | Hilal, Saima^{a; c; e; f; g; *}

Affiliations: [a] Memory Aging & Cognition Centre, National University Health System, Singapore, Singapore | [b] Ageing Research Institute for Society and Education, Nanyang Technological University, Singapore, Singapore | [c] Department of Pharmacology, National University of Singapore, Singapore, Singapore | [d] Raffles Neuroscience Centre, Raffles Hospital, Singapore, Singapore | [e] Department of Radiology and Nuclear medicine, Erasmus University Medical Center, Rotterdam, The Netherlands | [f] Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands | [g] Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore

Correspondence: [*] Correspondence to: Dr. Saima Hilal, Department of Pharmacology, National University of Singapore, BLK MD3 Level 4 #04-01, 16 Medical Drive, Singapore 117600. Tel.: +65 6516 5056; Fax: +65 65165885; E-mail: [email protected].

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

Abstract: Background:Cerebral microbleeds (CMBs) in the lobar and deep locations have been associated with two distinct pathologies namely cerebral amyloid angiopathy (CAA) and hypertensive arteriopathy. However, the role of mixed-location CMBs in cerebrovascular disease and cognitive impairment remain unexplored. Objective:The present study aims to investigate the association of strictly lobar, strictly deep and mixed-location CMBs with cognitive impairment and dementia as well as functional decline. Methods:A prospective case-control study, where 520 patients underwent 3T brain MRI to assess region and lobe-specific CMBs, and other cerebrovascular diseases (CeVD) markers such as cortical infarcts, lacunes, and white matter hyperintensities. Patients were classified as no cognitive Impairment, cognitive impairment no dementia (CIND), and dementia [Alzheimer’s disease (AD) and vascular dementia (VaD)]. Severity of cognitive impairment was assessed using Clinical Dementia Rating scale. Results:Mixed-location CMBs were associated with dementia [Odds ratio (OR):1.23; 95% confidence interval (CI):1.04, 1.47]. When stratified by the presence of CeVD, mixed-location CMBs were associated with CIND [OR:1.20;95% CI:1.02, 1.42], AD [OR:1.22;95% CI:1.02, 1.46], and VaD [OR:1.33;95% CI:1.08, 1.62]. Furthermore, CMBs in frontal, parietal, and temporal regions were associated with CIND whereas those in parietal, temporal, and occipital regions were associated with AD. Mixed-location CMBs were also associated with increased severity of cognitive impairment [OR:1.02; 95% CI:1.00, 1.05]. Conclusion:Mixed-location CMBs are associated with cognitive impairment and dementia in the presence of CeVD. Furthermore mixed-location CMBs were linked with increased severity of cognitive impairment, suggesting severe parenchymal damage as well as microangiopathy to be common underlying mechanisms in the elderly.

Keywords: Alzheimer’s disease, cerebral microbleeds, cerebrovascular disease, cognition, mixed-pathology

DOI: 10.3233/JAD-190540

Journal: Journal of Alzheimer's Disease, vol. 71, no. 4, pp. 1309-1320, 2019