The PREVENT study: a prospective cohort study to identify mid-life biomarkers of late-onset Alzheimer's disease

Introduction: Epidemiological studies indicate that significant decreases in the incidence of Alzheimer's disease (AD) may be obtained by targeting multiple middle-age risk factors. However, as dementia is unlikely to be diagnosed for decades, short-term outcome measures are required. AD biomarker changes precede clinical symptoms by many years, but their sensitivity to mid-life change remains unknown. Methods and analysis: PREVENT is a prospective cohort study examining biomarker status at mid-life in at least 150 individuals genetically at high, medium or low risk of late-onset AD. Participants are children of individuals with or without a diagnosed AD allocated to high, medium and low-risk groups according to parental clinical status and ApoE genotype. The biomarkers examined over 2 years are plasma and CSF A beta 42 amyloid, Tau and pTau, proinflammatory cytokines, acute-phase proteins, medial temporal-lobe atrophy, white matter lesion volume, cognitive performance related to transentorhinal and hippocampal functioning and hypothalamic-pituitary-adrenal and sympathetic axes regulation. Ethics and dissemination: Detected pathologies are communicated to the participant's general practitioner with their permission. Risk status by genotype would not be revealed. The results of the study would be published in peer-reviewed journals and validated biomarkers used to construct a randomised controlled intervention study.