Externalizing Behaviors and Alzheimer's Disease and Any Dementia: A Multigeneration Cohort Study in Sweden

Background and Objectives We examined the extent to which externalizing behaviors such as violent and nonviolent criminal behavior, and substance use disorders (SUD) are associate with the onset of Alzheimer's disease (AD) and any dementia in prior generations.Research Design and Methods A nationwide cohort of 2,463,033 individuals born between 1973 and 1997 (index persons) were linked to their biological relatives (parents, grandparents, and uncles/aunts) using Swedish national registers. Cox regression models were used to examine the association between each measure of externalizing behaviors with AD and any dementia in each of the relative cohorts.Results Parents of index persons with externalizing behaviors had an increased risk for AD compared with parents of index persons without externalizing behaviors-nonviolent criminal behavior: Hazard Ratio (HR) = 1.16, 95% Confidence Intervals (CI) 1.10-1.22; violent criminal behavior: HR = 1.32 (95% CI: 1.19-1.45); SUD: HR = 1.28 (95% CI: 1.17, 1.40). The associations attenuated with decreasing familial relatedness. Relatives of individuals with externalizing behaviors compared with relatives of individuals without, showed an increased risk of having both early-onset and late-onset AD but the strength of the associations was higher for early-onset AD than for late-onset AD. A similar pattern of results was observed for the association with any dementia.Discussion and Implications Externalizing behaviors are associated with AD and any dementia in prior generations. The associations were stronger for parents in comparison with grandparents and uncles/aunts, suggesting shared familial risks between conditions. This warrants further studies examining common genetic and family-wide environmental factors that may contribute to identifying common underlying mechanisms to the development of externalizing behaviors, AD, and any dementia.