The association between cognitive function and mortality is of increasing interest. We followed 1870 men aged 55-69 years at cognitive assessment for 16 years to establish associations with all case and cause specific mortality. Cognitive assessment included AH4, 4 choice reaction time (used as estimates of mid-life cognition) and the National Adult Reading Test (used as an estimate of early-life cognition). Causal models were tested for the effects of a) early-life cognition, b) confounding through mid-life disease, and c) the effects of sociodemographic and lifestyle factors. A fully adjusted model was also tested. Age adjusted associations with mid-life cognitive function were found with mortality from circulatory, coronary, respiratory and digestive disease but not from cancer mortality. Age adjusted associations were attenuated and in some cases nullified by further adjustment for each of early-life cognition, mid-life disease risk and sociodemographic and lifestyle factors. These associations cannot be assumed to be unbiased estimates of effect due to the complex confounding structures that exist in these data. Future studies should explore natural experiments, use different populations where the confounding structures may be different and evaluate more complex methods that may be able to deal with the inherent complexities of a life course perspective. (Contains 3 tables and 2 figures.)