Purpose and Overview

Chronic disease risk factors vary in their association with health outcomes such as mortality and cognition depending on when they are measured in the life course. Blood pressure, body mass index and cholesterol each show associations with later life outcomes (mortality, physical performance, cognition) that attenuate, disappear or reverse direction depending on the age at which the exposure is measured. This session examines why that reversal occurs and distinguishes three explanations for it: reverse causation, selective survival, and age-related effect modification. Each implies a different clinical action, so it is critical to identify the true source of the association. Evidence is drawn from life-course cohorts with repeated measurement beginning in childhood, from Mendelian randomization studies, and from randomized trials. The session closes with the practical consequences for clinical assessment in primary care, using an example association of blood pressure and cognitive performance, where the instrument in routine use discards most of the information generated by the assessment task itself. Recommendations for improvement are provided.