Subjective sleep traits and cognition across mid- to late-adulthood: a cross-sectional study of gene-environment...

Genetic susceptibility to Alzheimer's disease (AD) may influence the extent to which environmental factors shape cognition, with individuals at higher genetic risk potentially exhibiting greater sensitivity to environmental exposures. Sleep, an important factor for both cognitive function and AD risk, may further moderate genetic influences (A), including both measured (AP) and latent (AL) components, as well as shared (C) and non-shared environmental (E) contributions to cognition. This study leveraged data from the Interplay of Genes and Environment across Multiple Studies consortium (N = 3894; 1947 complete twin pairs, 842 monozygotic (MZ) pairs and 1105 dizygotic (DZ); Average age = 62.36 years, 38.75% female). Across six cognitive abilities, we examined whether an AD polygenic score (AD-PGS) moderated environmental influences on cognitive performance. We also examined whether sleep moderated genetic and environmental contributions on cognitive performance. Although the AD-PGS accounted for a negligible proportion of genetic variance as a main effect (B's = -0.004 to 0.02), we observed environment-by-PGS interactions. Increasing genetic risk for AD was associated with lower contributions from environmental experiences unique to each individual, on episodic memory, working memory, and verbal ability (B's = -0.03 to -0.05). These interaction effects, albeit small, were primarily observed with the AD-PGS including the APOE region. Hence, the role of person-specific environments on cognitive functioning was boosted for those at lower genetic risk for AD but reduced at greater genetic risk for AD. Although sleep moderation was minimal, results suggest that poorer sleep influences genetic influences on cognitive functioning. Statement of Significance This study provides novel insights into how genetic risk for Alzheimer's disease (AD-PGS), and sleep (duration and disturbances) moderate genetic and environmental contributions to cognitive performance. Although the AD-PGS accounts for minimal genetic variance, significant but small environment-by-PGS interactions emerged. Individuals with higher AD-PGS exhibited heightened responsiveness to nonshared environmental influences on episodic memory, working memory, and verbal ability, primarily driven by the APOE ε4 region. Poorer sleep may be associated with subtle variations in genetic contributions to cognition, though moderation effects were minimal. This work offers insight into the genetic mechanisms underlying sleep, AD risk, and cognition, underscoring the need to consider both genetic susceptibility and environmental influences when examining factors that contribute to individual differences in cognition.