Determining Causation from Observational Studies: A Challenge for Modern Neuroepidemiology

While epidemiology is the study of frequencies, trends, and determinants of disease in specified populations, the overriding aim of epidemiology is to apply such knowledge to prevention. Both primary and secondary prevention benefit from a detailed understanding of risk factors that can be uncovered through careful epidemiological research. Clearly some factors associated with outcomes in cross-sectional studies may be risk factors, but also may not, and indeed may not be in longitudinal studies. While risk factors are causal, some are modifiable and some not. But some risk factors that we have long regarded as fixed and not modifiable, such as genetics, have more recently, in the exploding science of epigenetics, been shown to be more or less expressed through different lifestyles. Ornish et al. has shown for example that intensive lifestyle changes favorably modulate gene expression in prostate cancer (1) and, with Nobel laureate Elizabeth Blackburn, that such environmental factors can reverse what was thought to be an inevitable decline in telomere length associated with aging and disease (2).