The APOE epsilon4 allele has been associated with a number of neurodegenerative disorders e.g. Alzheimer's disease. Inconsistent results have been obtained for cognitive decline in 'normal' aging. We investigated whether specific aspects of cognitive decline were associated with APOE epsilon4 among 620 'healthy' elderly subjects living in Calabria, southern Italy. MMSE scores ranged from 11 to 30. A lower MMSE score was unrelated to APOE polymorphism, i.e. a global measure of cognition. However, poorer episodic memory was associated with APOE epsilon4, both registration (p=0.01) and recall (p=0.01). Temporal and spatial orientation, attention and calculation, language, and constructive function were not affected. We conclude that episodic memory, specifically, is adversely affected by APOE epsilon4 and urge evaluation of precise phenotypes in genetic association studies of cognitive decline in order to avoid inconsistent results due to phenotypic heterogeneity.