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.