Emerging evidence suggests that individual differences in cognitive aging unfold across a lifetime; however, relatively little is known as to how early life versus proximal influences accumulate to impact cognitive functioning across midlife. The Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife) seeks a greater understanding of the environmental and genetic factors that drive increasing divergence in cognitive maintenance. CATSLife comprises the prospective Colorado Adoption Project (CAP) and parallel Longitudinal Twin Study (LTS), now tested at ages 28-45 years (CATSLife1). We propose a 5-year follow-up of 1400 adoptive and nonadoptive probands, siblings, and twins as they navigate the transition to midlife at ages 33-50 years (CATSLife2). Whereas CATSLife1 established baseline performance as participants prepare for transitions to midlife, CATSLife2 proposes to evaluate stability and change across the midlife transition. Further, we propose to integrate the prospective Twins Early Development Study (TEDS) with a new assessment of 5000 twins at age 28 years, allowing us to build on over 20 years of prior data collection, including genome-wide genotyping, to explore similar predictors of cognitive maintenance. As participants transition to midlife, we will leverage powerful design features and a wealth of prospective data collected from infancy through adulthood, including a full adoption design, to examine causal implications of early environmental risk and protective factors, and a twin design to examine environmental factors that may have causal influence on cognition, controlling for familial confounds. As we leverage data from prior assessments with CATSLife1, the opportunity to investigate the transition across midlife with CATSLife2 is ideal. We will use our twin/adoption design with polygenic score data (PGS), detailed cognitive batteries, physical health, proposed biomarkers of accelerated aging that may participate in immune- inflammatory and neurotransmitter pathways, and neighborhood features to shed light on risk-resilience factors that account for midlife cognitive stability and change. This integrated follow-up study of CATSLife and TEDS aims to: 1) Evaluate individual differences in stability and change of cognitive abilities in midlife, considering cognitive reserve pathways vis-a-vis genetic and genetically mediated environmental influences; 2) Evaluate genetic factors with lifestyle and health behaviors that predict cognitive stability and change, considering early life reserve and genetic moderation; 3) Evaluate biomarkers of accelerated aging as predictors and mediators of cognitive stability and change, uniquely characterizing biomarker patterns and change at the midlife transition; and 4) Evaluate stressful and buffering contextual factors that predict cognitive stability and change, addressing individual socio-demographics and neighborhood features, accounting for active (rGE) selection. The findings from this proposed CATSLife/TEDS follow-up study could substantially increase our understanding of the genetic and environmental etiologies of individual differences in cognitive aging.

The continuation of this unparalleled combined adoption/twin study will contribute to a greater prospective understanding of the manner in which cognitive abilities, physical health, and neighborhood environments promote cognitive functioning at midlife. A fuller understanding of genetic and environmental influences, and how they interact with early life factors to affect midlife cognitive functioning, may contribute to improved cognitive health as well as to better health education and services.