The presence of the apolipoprotein E e4 allele has been considered to be a risk factor for Alzheimer's disease and vascular dementia. We therefore used demanding neuropsychologic testing and brain MRI to determine if elderly normals with at least one e4 allele demonstrate subclinical changes in cognition and a higher frequency of brain atrophy or silent ischemic brain damage. The study population consisted of 214 randomly selected individuals aged 50 to 75 years without neuropsychiatric or general disease. There were 175 (81.8%) subjects without and 39 (18.2%) with at least one e4 allele. The two groups were comparable for age, length of education, verbal intelligence, mood and major vascular risk factors. Apolipoprotein E e4 carriers performed significantly worse than non-carriers when assessed for learning and memory abilities, while there were no differences in test results of conceptualization, attention, speed of mental processing and visuopractical skills. There were no between-group differences for thromboembolic and lacunar infarcts, white matter hyperintensity grading and the semiautomatically measured white matter hyperintensity area. The extent of sulcal and ventricular widening as well as hippocampal and parahippocampal volumes were also similar between the comparative subsets. We conclude that the apolipoprotein E e4 allele is associated with subtle learning and memory deficits in normal elderly persons and may therefore be suggested a marker for accelerated cognitive aging. In this group of subjects it was not associated with brain parenchymal changes as demonstrated by MRI.