Early Onset Alzheimer's Disease and Related Dementias: A Population-Based Approach to Identify Characteristics and Risk Factors

Summary Alzheimer's Disease and Related Dementias (ADRD) is an overwhelming medical condition at any age, but ADRD in younger adulthood is particularly devastating, affecting quality of life and independence of individuals in their prime years. Early onset ADRD (EOD) is defined as an ADRD diagnosis before age 65. While it is

commonly perceived that EOD occurs primarily as a rare genetic syndrome, the known genetic variants account for less than 5% of cases. Despite the distressing course and unclear nature of the disease in the majority of cases, EOD is widely understudied. Current data on the prevalence and incidence of EOD seem to

underestimate the magnitude of the problem and there is no information available regarding predisposing and/or protective factors for EOD. Using the infrastructure of an international Dementia Risk Pooling Project (DRPP), we propose a prospective study of EOD development which comprises individuals from five large multi-ethnic population-based cohort

studies (ARIC, MESA, FHS, Whitehall II and, UK Biobank). This study provides the opportunity to (1) refine estimates of incident EOD, (2) investigate the role of cardiovascular, lifestyle and behavioral risk factors in the onset of EOD and (3) study whether a favorable midlife risk profile in the presence of genetic predisposition

delays EOD age of onset. This evaluation will be the first study to pool multiple international population-based cohorts to prospectively study ADRD before the age of 65 in young and middle-aged adults. The current notion that EOD is merely driven by genetic syndromes has shadowed efforts to identify distinct predisposing and/or

protective factors for EOD and targeting vulnerable populations for early detection and prevention. The findings will shed much needed light on the vulnerability and unique risk factors for EOD and may lead to development of more effective targets for prevention to delay onset and progression of disease. EOD is relatively rare and

thus primordial and primary prevention may be more efficient than screening and secondary or tertiary prevention. Our data on EOD risk factors will strengthen targeted intervention strategies with focus on primordial and primary prevention.