Diabetes mellitus, glycemic traits, and cerebrovascular disease: a Mendelian randomization study

Abstract:

Background And Aims Whether cerebral microbleeds (CMBs) cause cognitive impairment remains uncertain. We determined whether CMBs are associated with cognitive dysfunctions in patients with symptomatic small vessel disease (SVD). Methods DNA-Lacunar-2 is recruiting 1000 patients with MRI-confirmed lacunar stroke from 54 UK centres. Here we report results for the first 575 included patients. CMBs were graded using the Brain Observer Microbleed Rating Scale (BOMBS). Neuropsychological assessment was performed using the Brief Memory and Executive Test (BMET). Using linear regression models adjusted for age and sex, we analysed the association between CMBs and global cognitive performance, as well as executive function/processing speed (EF/PS) and orientation/memory (OM) domains. Results Of the 575 patients, 422 had both susceptibility-weighted images and complete cognitive data; CMBs were detected in 109/422 (25.8%). Both presence and number of CMBs were significantly associated with impaired global cognitive performance [β = -16.17; 95%CI = (-31.73;-0.61) and β = -12.03; 95%CI = (-20.20;-3.88), respectively]. On analysis of specific cognitive domains, the associations were present for EF/PS [β = -6.59; 95%CI = (-10.89;-2.29) and β = -4.00; 95%CI = (-6.25;-1.75), respectively], but not for OM [β = -0.59; 95%CI = (-4.87;3.69) and β = -1.39; 95%CI = (-3.64;0.86), respectively]. Additionally adjusting for WMH severity and lacune count, the association between presence and number of CMBs and impaired EF/PS remained significant [β = -4.79; 95%CI = (-9.39;-0.19) and β = -3.07; 95%CI = (-5.53;-0.61), respectively]. Conclusions In a large cohort of symptomatic SVD patients, after controlling for other neuroimaging markers of SVD severity, CMBs were associated with impaired executive function and processing speed. This might suggest a causal role of CMBs in vascular cognitive impairment. The full dataset of 1000 cases recruited to DNA-Lacunar-2 will be presented at ESOC 2020.