Background:We examined the hypothesis that deficits in learning, memory, and other cognitive functions are associated with the epsilon4 allele of the Apolipoprotein E (APOE) gene in a non-demented sample with memory complaints recruited from a population with a high prevalence of this allele. Methods:The study group comprised 70 consecutively referred patients aged 50-75 seeking assessment due to memory complaints. They were screened for dementia, for neurological and psychiatric disease, and for cerebral infarction using Magnet Resonance Imaging (MRI). Participants were classified as non-demented based on clinical evaluation and results on cognitive tests. Results:APOE epsilon4 carriers (56% of the sample) showed poorer performance than non-carriers on the Mini Mental State Examination, a number of measures of verbal memory function from the California Verbal Learning Test, and visual recall. In 46% of the participants, psychometric criteria for amnestic Mild Cognitive Impairment (aMCI) were satisfied.Conclusions:Findings may be partly explained by a significant number of participants being in a preclinical phase of Alzheimer's disease. The observed deficits in learning performance and the lack of significant age modulation of the genetic association suggest a more general genetic effect. The findings are consistent with known neurobiological function of APOE epsilon4, including both increased risk of neurodegenerative disease and reduced synaptic integrity in older age.