[P1–410]: HIGHER PREVALENCE OF CEREBRAL WHITE MATTER HYPERINTENSITIES IN HOMOZYGOUS APOE‐ε4 ALLELE CARRIERS AGED 45 TO 75: RESULTS FROM THE ALFA STUDY

Cerebral white matter hyperintensities (WMH) are believed to be the consequence of small vessel disease and are associated with risk and progression of Alzheimer's disease (AD). The ε4 allele of the Apolipoprotein E (APOE) gene is the major factor accountable for AD heritability. However, the relationship between WMH and APOE genotype in healthy subjects remains controversial. We aimed at investigating the association between APOE-ε4 and vascular risk factors with WMH, and explore their interactions, in the Alzheimer and Families (ALFA) cohort of cognitively healthy adults (45–75 years). WMH were assessed with the Fazekas Scale from magnetic resonance images (575 participants: 74 APOE-ε4 homozygotes, 220 APOE-ε4 heterozygotes and 281 noncarriers) and individuals classified into normal (Fazekas<2) and pathological (≥2). In addition to APOE, cardiovascular risk factors were recorded and cardiovascular and dementia risk scores computed. Stepwise logistic regression analysis was used to study the association between pathological Fazekas and APOE genotype after correcting for cardiovascular and sociodemographic factors. APOE-ε4 homozygotes, but not heterozygotes, bear a significantly higher risk (OR 3.432; 95% CI [1.297–9.082]; p=0.013) of displaying pathological WMH, which is independent of cardiovascular risk factors effect. As expected, age, hypertension and cardiovascular and dementia risk scales were also positively associated to pathological WMH. Cognitively healthy late-middle aged APOE-ε4 homozygotes show a higher risk of presenting pathological WMH. The control of modifiable risk factors in individuals at higher risk of developing WMH might represent a preventive strategy to reduce or delay dementia's onset.