The aim of the project is to investigate whether behavioural (smoking, alcohol consumption, physical activity, sleep), physical (body mass index, blood pressure), ill health and its indicators (diabetes, vascular problems, asthma, leukocyte count), lifestyle (socioeconomic position) and cognitive (brain structure and volume, processing speed and memory) factors mediate the relationship between intelligence and Alzheimer’s disease. Observational and genetic studies of modifiable risk factors for Alzheimer’s disease is inconsistent, with studies reporting null, positive or negative findings for the same risk factor. Educational attainment and intelligence are the only risk factors to have been consistently related with Alzheimer’s disease, with both observational and Mendelian randomization studies reporting greater educational attainment and intelligence to be associated with a lower risk of Alzheimer’s disease. Recently, we showed there was little evidence of an effect of a direct effect of educational attainment of Alzheimer’s disease once intelligence was accounted for. In the time
span of 36 months, we will aim to identify the factors mediate the effects of intelligence on Alzheimer’s disease. Given that we are currently unable to delay or reverse progression of dementia, prevention is crucial. If we were able to identify factors on which intervention might reduce the risk of dementia, the psychological trauma of diagnosis, potentially unsuccessful treatments, and the experience of gradual cognitive decline could be minimised. Intelligence is largely hereditary and quite difficult to intervene on. For this reason, it is necessary to understand how intelligence protects people against dementia and identify factors that lie on the causal pathway between intelligence and Alzheimer’s disease (i.e. mediators) to provide additional targets for intervention. It is plausible that higher intelligence is associated with, for example, greater physical activity, fewer risky healthy behaviours such as smoking and excessive alcohol consumption, lower body fat and a more favourable cardiovascular risk profile, which in turn may confer lower risk for Alzheimer’s disease.