IC‐P‐039: ApoE‐ε4 genotype by gender interactions in regional amyloid accumulation in Alzheimer's disease continuum

Background: Cerebral microhemorrhages (mH) are commonly found in aging populations and are associated with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). A previous study found an association between cerebral amyloid deposition and mH in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort [1]. The goal of this project was to evaluate the effect of cerebral amyloid deposition, measured using [F]Florbetapir, and a history of hyperlipidemia (HLD) on mH in cognitively normal older adults (CN), older adults with significant memory concerns (SMC), and patients with early and late MCI (EMCI; LMCI) and mild AD. Methods: 829 participants (177 HC, 75 SMC, 295 EMCI, 149 LMCI, 133 AD) were included. Demographic, clinical, medical history, mH data from T2* gradient recalled echo (GRE) scans (processed as in [1]), and [F]Florbetapir SUVR (processed as in [2], normalized to whole cerebellum) were downloaded from the ADNI site. Participants were divided by presence or absence of HLD history, amyloid positivity (positive is SUVR>1.1), and the interaction of these variables. mH were analyzed by number of regions showing mH (0, 1, 2, 3, 4, 5+) and by presence/absence of mH. Linear regression and chi-square models were used to assess the relationship of HLD history and amyloid positivity to mH, covaried for age. Results: Both amyloid positivity and HLD history were independently associated with presence/absence and number of regions showing mH (all p<0.05). Participants who were both positive for HLD history and amyloid showed the highest rate of mH positivity (39.2%), relative to those positive for only HLD history (22.5%), only amyloid positivity (28.5%), and those showing neither risk factor (19.3%). These effects were independent of baseline diagnostic group, gender, and APOE ε4 genotype. Conclusions: HLD and amyloid deposition are independent risk factors for mH and show an additive effect such that older adults who are both amyloid positive and have a history of HLD have the highest prevalence and number of mH. Future studies of the clinical implications and underlying mechanisms of these effects are warranted. [1] Kantarci et al. (2013) Alz & Dem, 9(5 Supp): S11623. [2] Landau et al. (2013) J Nucl Med, 54(1): 70-77.