Abstract
Dementia is a worldwide health priority, with increasing public health burden and thus need for preventive strategies. Although many associations are proposed, there has been lack of sufficient evidence or demonstration of modifiability. This review will discuss the methodological challenges and the most established, controversial and novel modifiable midlife risk factors. There has been a shift towards a life-course approach, with large cohort longitudinal studies helping to untangle 'windows of opportunity' or reverse causation with vascular factors (hypertension and BMI), hormone replacement therapy and depression. Other vascular factors, such as hyperglycaemia, have now been approached as a continuum and BMI/alcohol as U-shaped associations. There is evidence regarding associations or mechanisms for personality, insomnia, cognitive stimulation and social activities, head injury, diet, and reproductive and oral health. Environmental considerations such as passive smoke, noise and hygiene exposure are also explored. Increasing evidence of associations from midlife will guide the shift to interventional studies from the midlife period. However, research challenges are such that the ideal studies may be impossible, although, for numerous factors, it has been argued that other known adverse health effects justify initiating or continuing health interventions in the absence of this evidence.
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