Risk factors for Alzheimer's disease and related dementia: A lifecourse approach

Alzheimer's disease and related dementias are devastating for the individual and their entourage, they also carry tremendous financial burden for society at large. Age is the principal risk factor, with the risk doubling every 5 years after the age of 65 years. Research has clearly established that pathophysiological changes occur ten to fifteen years before the diagnosis of disease. This has implications for understanding risk and protective factors of the disease as most longitudinal studies were set up in adults over 65 years of age at the start of the study and the follow-up for incidence of Alzheimer's disease is often less than ten years. Thus, the results from such studies are likely to be biased by reverse causation. This has led to inconsistent findings in studies and a varying list of risk and protective factors produced by various guidelines published in recent years. In this paper, we describe these challenges and propose the use of a lifecourse approach for the identification of risk and protective factors. We also highlight the need to extend research on biomarkers to peripheral biomarkers; proteomics, in particular, as they reflect both genetic and environmental effects and are potentially modifiable. (C) 2020 l'Academie nationale de medecine. Published by Elsevier Masson SAS. All rights reserved.