APOE and Mental deterioration: Toward this end, our findings are in line with the view that the total burden of cerebral mixed vascular and neurodegenerative alterations is the strongest determinant of cognitive phenotypes in aging.15,30, –, 32 The interactive effect of SVD load with APOE ε4 allele on cognitive decline is consistent with findings of interactions between APOE ε4 allele and individual markers for microvascular (e.g., WMH) and neurodegenerative (e.g., neuritic plaques and neurofibrillary tangles) lesions on cognitive phenotypes in aging.8,10,33,34