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Background: The APOE epsilon4 allele is an established risk factor for Alzheimer disease (AD), yet findings are mixed for how early its effects are manifest. One reason for the mixed results could be the presence of interaction effects with other AD risk factors. Increasing evidence indicates that testosterone may play a significant role in the development of AD. The aim of the present study was to examine the potential interaction of testosterone and APOE genotype with respect to hippocampal volume in middle age., Methods: Participants were men from the Vietnam Era Twin Study of Aging (n = 375). The mean age was 55.9 years (range 51-59). Between-group comparisons were performed utilizing a hierarchical linear mixed model that adjusted for the nonindependence of twin data., Results: A significant interaction was observed between testosterone and APOE genotype (epsilon4-negative vs epsilon4-positive). Those with both low testosterone (> or =1 SD below the mean) and an epsilon4-positive status had the smallest hippocampal volumes, although comparisons with normal testosterone groups were not significant. However, individuals with low testosterone and epsilon4-negative status had significantly larger hippocampal volumes relative to all other groups. A main effect of APOE genotype on hippocampal volume was observed, but only when the APOE-by-testosterone interaction was present., Conclusions: These findings demonstrate an interaction effect between testosterone and the APOE epsilon4 allele on hippocampal volume in middle-aged men, and they may suggest 2 low testosterone subgroups. Furthermore, these results allude to potential gene-gene interactions between APOE and either androgen receptor polymorphisms or genes associated with testosterone production.

An analogy is always imperfect. Nevertheless, at times it is an effective way to communicate an insight. This paper uses an analogy to examine the consequences of attempting to achieve health sector efficiency through regulation, instead of consumer cost-sharing. It is suggested that as long as hospital care continues to be virtually "free" to patients at the time of use, such regulation may well do more harm than good. Moreover, a national health insurance plan that would make all medical care "free" to patients, and would pay for all health care through taxes (the proposed Health Security Act), would not only generate significant inefficiency; but, in contrast to the intentions of its supporters, would prove harmful to the poor and the elderly, by shifting scarce Federal tax dollars away from the programs that assist them in order to pay the medical bills of middle and upper income households. It is therefore urged that we enact income-related catastrophic national health insurance, that would place a ceiling, which varies with household income, on the financial burden a household must bear; but at the same time, would require most families to pay part of their own medical cost out-of-pocket, so that consumer cost-consciousness can help promote health sector efficiency.