Older age and the apolipoprotein e4 (APOE4) genotype are the leading constitutional risk factors for AD, yet modifiable vascular-related risk factors are associated with additional late-life risk of AD [24, 30, 37, 43], dementia risk [1, 12, 14, 34, 38, 41, 47] and AD pathology biomarkers in preclinical older-age individuals [31, 39, 42]. This evidence concerns the gene APOE and Alzheimer disease.