Trajectories of imaging markers in brain aging: the Rotterdam Study

With aging, the brain undergoes several structural changes. These changes reflect the normal aging process and are therefore not necessarily pathologic. In fact, better understanding of these normal changes is an important cornerstone to also disentangle pathologic changes. Several studies have investigated normal brain aging, both cross-sectional and longitudinal, and focused on a broad range of magnetic resonance imaging (MRI) markers. This study aims to comprise the different aspects in brain aging, by performing a comprehensive longitudinal assessment of brain aging, providing trajectories of volumetric (global and lobar; subcortical and cortical), microstructural, and focal (presence of microbleeds, lacunar or cortical infarcts) brain imaging markers in aging and the sequence in which these markers change in aging. Trajectories were calculated on 10,755 MRI scans that were acquired between 2005 and 2016 among 5286 persons aged 45 years and older from the population-based Rotterdam Study. The average number of MRI scans per participant was 2 scans (ranging from 1 to 4 scans), with a mean interval between MRI scans of 3.3 years (ranging from 0.2 to 9.5 years) and an average follow-up time of 5.2 years (ranging from 0.3 to 9.8 years). We found that trajectories of the different volumetric, microstructural, and focal markers show nonlinear curves, with accelerating change with advancing age. We found earlier acceleration of change in global and lobar volumetric and microstructural markers in men compared with women. For subcortical and cortical volumes, results show a mix of more linear and nonlinear trajectories, either increasing, decreasing, or stable over age for the subcortical and cortical volume and thickness. Differences between men and women are visible in several parcellations; however, the direction of these differences is mixed. The presence of focal markers show a nonlinear increase with age, with men having a higher probability for cortical or lacunar infarcts. The data presented in this study provide insight into the normal aging process in the brain, and its variability.