Relationship between APOE Genotype Status and Imaging Features in Patients with Alzheimer Disease Being Considered for Antiamyloid β Therapy.

BACKGROUND AND PURPOSE: Alzheimer disease (AD) is a progressive neurodegenerative disorder that predominantly affects the aging population. Anti-amyloid β (anti-Aβ) therapies, such as lecanemab, have been developed to slow disease progression. However, their use is occasionally associated with amyloid-related imaging abnormalities (ARIA), posing prominent clinical challenges. It has been shown that apolipoprotein E (APOE)-ε4 genotype is strongly associated with an increased risk of microhemorrhages in AD, but the influence of specific APOE genotypes on imaging features important for anti-Aβ therapy remains unclear. This study explores the association between APOE genotypes and key imaging biomarkers in patients being considered for lecanemab treatment. MATERIALS AND METHODS: This retrospective study evaluated patients with AD who underwent APOE genotyping and were considered for lecanemab therapy. Key assessments included microhemorrhage counts, white matter hyperintensity (WMH) scores, perivascular space (PVS) evaluations, and cognitive function. Microhemorrhages were identified based on both SWI and GRE sequences in each patient. Six radiologists blinded to the patient's APOE genotype status independently conducted the imaging analyses. RESULTS: A total of 85 patients were included in the study with rare genotypes excluded from analysis (3 patients). Among the common genotypes, e3/e4 was the most prevalent (55%). Statistical analysis revealed significant association between APOE genotype and microhemorrhage count based on the SWI and GRE sequences (P = .007 and P = .003, respectively). The mean identified microbleed count was 1 (based on SWI) and 0.5 (based on GRE) in the same cohort of patients, with the following genotype-specific means based on SWI sequence: e3/e3 = 0.7; e3/e4 = 0.6; and e4/e4 = 2.7. No significant associations were found between APOE genotype and Montreal Cognitive Assessment, WMH or PVS scores. Post hoc power analysis showed adequate power for SWI-based microbleed detection but low power for WMH and PVS. CONCLUSIONS: In this cohort of patients with AD being evaluated for lecanemab therapy, a significant association was identified between APOE genotype and the number of microhemorrhages with higher mean counts of microbleeds detected on SWI sequence compared with microbleeds detected on the GRE sequence of the same patients. No significant associations were found between APOE genotype and WMH, PVS, or cognitive impairment.