Morphological changes in aging brain structures are differentially affected by time-linked environmental influences despite strong genetic stability

Abstract

This longitudinal study used the full twin model to estimate change and stability of genetic contributions to morphology of two brain structures, the corpus callosum and lateral ventricles. The 142 subjects were 34 monozygotic (MZ) and 37 dizygotic (DZ) elderly male twin pairs from the National Heart, Lung, and Blood Institute (NHLBI) Twin Study who underwent brain magnetic resonance imaging twice, separated by a 4-year interval. Genetic factors accounted for a substantial portion of individual differences in the size of the corpus callosum and its substructures and of lateral ventricular size. Longitudinal genetic analyses revealed no significant change in the heritability of these structures and no evidence for new genetic variance at Time 2 not present at Time 1. However, both the callosal and ventricular measures showed evidence for new environmental variance at Time 2 not present at Time 1. Confirming a previously posed hypothesis, the phenotypic correlation between absolute change in height of the corpus callosum and absolute change in ventricular volume was significant. Bivariate genetic analysis estimated a significant genetic correlation between the changes in these two structures and the genetic variance in the change of callosal height was entirely due to genes involved in the expansion of ventricles. Genetic stability was present even in old age when brain and other morphological changes can be rapid and highly variable across individuals, inconsistent with an hypothesis that random DNA damage is the cause of aging.