The association of Apolipoprotein E ε4 with symptomatic intracerebral hemorrhage, MRI markers and cognition in Dutch-type hereditary cerebral amyloid angiopathy.

BACKGROUND: Apolipoprotein E (APOE) genotype influences the presence, course and severity of sporadic cerebral amyloid angiopathy (sCAA). We investigated the effect of the APOE ε4-allele on clinical and neuroradiological outcomes in mutation-carriers with Dutch-type hereditary (D-)CAA.

METHODS: Participants with D-CAA from a prospective cohort study, with data collected on history of symptomatic intracerebral hemorrhages (sICH) and vascular risk factors, underwent 3 Tesla magnetic resonance imaging (MRI) scans to assess macrobleeds, cerebral microbleeds (CMBs), cortical superficial siderosis (cSS), enlarged perivascular spaces (EPVS), white matter hyperintensity (WMH) volume and WMH multispot lesions. Global cognition was measured using Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) scores. Associations between ≥1 APOE ε4-allele and age of first sICH, time to recurrence, cognition and radiological data were analyzed with adjustments for confounders.

RESULTS: Eighty-one participants (mean age 47 years, 54% women, 38% with sICH history) were included. The APOE ε4-allele was not associated with earlier sICH onset (median age 56 versus 57 years; p = 0.6) or time to recurrence (5.0 versus 3.9 years; p = 0.4), nor was it associated with macrobleeds (β 2.0; 95%CI 2.4- -2.7; p = 0.4), CMBs (β 2.9; 95%CI 1.0-8.9; p = 0.06), cSS (aOR 0.5; 95%CI 0.1-2.0; p = 0.3), EPVS (aOR 0.4; 95%CI 0.1-1.5; p = 0.6), WMH volume (β 6.8; 95%CI -1.9-15.4; p = ), a multispot pattern (OR 0.7; 95%CI 0.2-2.7, p = 0.6), or cognition (β -0.3; 95%CI -0.4- -0.5; p = 0.5).

CONCLUSION: APOE ε4 does not affect key clinical parameters or D-CAA neuroradiological markers and therefore does not explain the large variation in disease course in D-CAA.