Distinguishing Lifelong Individual Differences from Divergent Aging Trajectories of Adult Brain Volumes

Abstract

Individual differences in the volumes of brain structures are often linked to various conditions, including Alzheimers disease, schizophrenia, and overall brain health. However, it remains unclear to what extent these differences reflect individual levels present from young adulthood or diverging aging trajectories from later ages. In this study, we analyze the aging dynamics of the volumes of six brain structures based on magnetic resonance imaging (MRI) scans from a large cross-cohort longitudinal sample of cognitively healthy adults (n = 8,311 with 18,520 MRIs, ages from 18 to 97 years). From general assumptions about structural brain dynamics and measurement noise, a stochastic dynamical model was fitted to the data to estimate both the variability and persistence of structural changes across adulthood. Using this model, we calculated how much of the variance of volumetric differences between individuals can be attributed to stable levels from young adulthood versus systematic changes at older ages, as well as the theoretical sensitivity of longitudinal studies to detect individual differences in change. The findings were as follows: 1) Before age 60 years, inter-individual differences in neuroanatomical volumes almost exclusively reflect stable differences between individuals, while the influence from systematic differences in rate-of-change increases thereafter; up to 50 % of the variation being due to differences in change at 80 years. In contrast, ventricular volume reflects differences in change from early adulthood. 2) Current brain-age models are unlikely to be sensitive to detect differences in aging trajectories. 3) Imaging studies have low reliability in detecting inter-individual brain changes before age 60. After 60 years, the study reliability increases sharply with longer intervals between scans and more modestly with additional intermediate observations. In conclusion, our results reinforce the view that it is critical to distinguish stable early-adulthood levels from systematic differences in change when studying adult brain aging.