Interaction of APOE genotype and testosterone on episodic memory in middle-aged men.

Age-related changes in testosterone are believed to be a key component of the processes that contribute to cognitive aging in men. The APOE-ε4 allele may interact with testosterone and moderate the hormone's association with cognition. The goals of the present study were to examine the degree to which free testosterone is associated with episodic memory in a community-based sample of middle-aged men, and examine the potential interaction between free testosterone and the APOE-ε4 allele. Data were used from 717 participants in the Vietnam Era Twin Study of Aging. Average age was 55.4 years (standard deviation = 2.5). Significant positive associations were observed between free testosterone level and verbal episodic memory, as well as a significant interaction between free testosterone and APOE-ε4 status. In ε4 carriers free testosterone was positively associated with verbal episodic memory performance (story recall), whereas no association was observed in ε4 noncarriers. Results support the hypothesis that APOE-ε4 status increases susceptibility to other risk factors, such as low testosterone, which may ultimately contribute to cognitive decline or dementia.