Additional Serum Tests at Baseline
Biomarker testing associated with stroke, intracranial bleed, thrombosis and dementia performed at enrollment and the 24-month visit included brain natriuretic peptide (BNP), troponin, growth differentiation factor (GDF)-15, cystatin-C, D-dimer, matrix metalloprotinease (MMP)-9, chemokine ligand 23 (CCL23), endothelial cell adhesion molecule (ESAM), plasma von Willebrand factor, C reactive protein (CRP), prothrombin fragment 1+2, P-selectin, factor VIII, protein C, protein S, anti-thrombin III, anti-beta-2 glycoprotein-1 IgG and IgM, anticardiolipin IgG and IgM, and lupus anticoagulant panel. Because the most common gene polymorphism associated with sporadic microbleeds is the Apolipoprotein E (APOE) gene on chromosome 19, to control for this variable we will test for this gene as well as and the APOE ɛ2 and ɛ4 alleles which have each been independently associated with lobar microbleeds 14-16. Neprilysin and the single-nucleotide polymorphism rs6656401 within the Complement Receptor-1gene that are associated with severe cerebral amyloid angiopathy will also be assessed 17, 18.

Statistical Analysis

Descriptive statistics were used to report the recruitment, study subject retention, budget adherence and likelihood of obtaining the desired outcomes from the pre-specified power analysis, safety, and identification of adverse effects.
For the primary outcomes, 2-year incident dementia and whether there was a significant change in ADAS-cog11 (increase of >30%) and DAD (score <50% and/or a 30% decrease) scores were evaluated using the chi-square statistic. In addition, change scores for ADAS-cog11 and DAD (2-year survey score minus baseline survey score) utilized the Student’s t -test and the Mann Whitney Rank Sum test. Comparisons of change scores between baseline and other time points (i.e., 6, 12, and 18 months) was used the Student’s t -test and Mann Whitney Rank Sum test to determine significant differences at these time points. Analyses was performed on an intention-to-treat basis.