Risk Factors for and Clinical Relevance of Incident and Progression of Cerebral Small Vessel Disease Markers in an Asian Memory Clinic Population

Article type: Research Article

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

Affiliations: [a] Memory Aging & Cognition Centre, National University Health System, Singapore | [b] Department of Pharmacology, National University of Singapore, Singapore | [c] Ageing Research Institute for Society and Education, Nanyang Technological University, Singapore | [d] Saint Luke’s Hospital, Singapore | [e] Raffles Neuroscience Centre, Raffles Hospital, Singapore | [f] Departments of Epidemiology and Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands

Correspondence: [*] Correspondence to: Saima Hilal, PhD, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Level 4, MD3, 16 Medical Drive, Singapore 117600, Singapore. Tel.: +31 638637766; E-mail: phchs@nus.edu.sg.

Note: [1] Joint last authors.

Abstract: Background:Cerebral small vessel disease (SVD) is one of the major contributors to cognitive impairment and dementia. However, data on the incidence and progression of SVD in an Asian population are lacking. Objective:The present study aims to investigate the incidence, progression, associated risk factors, and clinical relevance of SVD in a memory clinic setting. Methods:A prospective case-control study, where 346 patients underwent repeated brain MRI with a mean interval of 24.5 months, accessing white matter hyperintensities (WMH), lacunes and cerebral microbleeds (CMBs). Severity of cognitive impairment was assessed using Clinical Dementia Rating scale and change in clinical diagnosis. Data on demographics, vascular risk factors, and clinical history were collected at baseline. Results:The prevalence of significant WMH (Fazekas ≥2) was 56.6% at baseline which progressed to 59.0% at follow-up. Overall prevalence of CMBs increased from 42.2% to 47.4% (9% new cases) and lacunes increased from 31.8% to 33.2% (2.1% new cases). Hypertension was associated with WMH progression (OR: 1.78, 95% CI: 1.01, 2.99) and increasing age was associated with incident CMBs (OR: 1.04, 95% CI: 1.01, 1.08). Moreover, the use of lipid-lowering medications decreased the incidence of lacunes (OR: 0.15, 95% CI: 0.04, 0.61). The major risk factor for incident SVD was baseline SVD lesion load. WMH progression was associated with increased severity of cognitive impairment (OR: 1.95, 95% CI: 1.16, 3.23). Conclusion:Vascular risk factors and baseline severity of SVD lesion load were associated with progression of SVD. Furthermore, WMH progression was linked with increased severity of cognitive impairment. Future studies should be aimed to slow cognitive deterioration by preventing SVD related brain damage by targeting vascular risk factors.

Keywords: Cerebral small vessel disease, clinical dementia rating, cognitive impairment, magnetic resonance imaging, vascular risk factors

DOI: 10.3233/JAD-180911

Journal: Journal of Alzheimer's Disease, vol. 67, no. 4, pp. 1209-1219, 2019