Focal hemosiderin deposits and beta-amyloid load in the ADNI cohort

Abstract

Prevalence and incidence of focal hemosiderin deposits are important considerations for inclusion and tracking of adverse events in Alzheimer's disease (AD) therapeutic trials with amyloid-lowering agents. We report the prevalence and regional distribution of focal hemosiderin deposits in the form of microhemorrhages (mH) and superficial siderosis in cognitively normal (CN), early mild cognitive impairment (EMCI), late MCI (LMCI) and AD subjects in the Alzheimer's Disease Neuroimaging Initiative -Grand Opportunity (ADNI-GO) and ADNI-2 studies. We further investigate the number of mH in relation to APOE genotype and Aβ load on PET. Subjects were cognitively normal (n=171), EMCI (n=240), LMCI (n=111) and AD (n=40) ADNI-GO and ADNI-2 participants who underwent 3T MRI studies from June 2010 until March 2012. Microhemorrhages and superficial siderosis were assessed at baseline and on all available T2* gradient recalled echo (GRE) MRIs at 3, 6 and 12 months. β-amyloid load was assessed with 18 F-florbetapir PET. The correlation between mH count and age and 18 F-florbetapir SUVR was tested using Spearman rank-order correlation. Kruskal-Wallis test was used as a one-way nonparametric ANOVA to evaluate the association between mH count and APOE genotype classified as ε2 carriers, ε3/3 homozygotes, and ε4 carriers. Prevalence of superficial siderosis was 1% and prevalence of microhemorrhages was 25% increasing with age (p<0.001) and β-amyloid load (p<0.001). Topographic densities of microhemorrhages were highest in the occipital lobes and lowest in the deep/infratentorial regions (Figure). APOE ε4 carriers had greater odds than APOE ε3 homozygotes of having two (p=0.046) and three (p=0.03) or more mH. Greater number of microhemorrhages at baseline was associated with a greater annualized rate of additional microhemorrhages by last follow-up (rank correlation=0.49;P<0.001).