Investigating the impact of motion in the scanner on brain age predictions.

Brain Age Gap (BAG) is defined as the difference between the brain's predicted age and the chronological age of an individual. Magnetic resonance imaging (MRI)-based BAG can quantify acceleration of brain aging, and is used to infer brain health as aging and disease interact. Motion in the scanner is a common occurrence that can affect the acquired MRI data and act as a major confound in the derived models. As such, age-related changes in head motion may impact the observed age-related differences. However, the relationship between head motion and BAG as estimated by structural MRI has not been systematically examined. The aim of this study is to assess the impact of motion on voxel-based morphometry (VBM) based BAG. Data were obtained from two sources: i) T1-weighted (T1w) MRIs from the Cambridge Centre for Ageing and Neuroscience (CamCAN) were used to train the brain age prediction model, and ii) T1w MRIs from the Movement-related artifacts (MR-ART) dataset were used to assess the impact of motion on BAG. MR-ART includes one motion-free and two motion-affected (one low and one high) 3D T1w MRIs. We also visually rated the motion levels of the MR-ART MRIs from 0 to 5, with 0 meaning no motion and 5 high motion levels. All images were pre-processed through a standard VBM pipeline. GM density across cortical and subcortical regions were then used to train the brain age prediction model and assess the relationship between BAG and MRI motion. Principal component analysis was used to perform dimension reduction and extract the VBM-based features. BAG was estimated by regressing out the portion of delta age explained by chronological age. Linear mixed-effects models were used to investigate the relationship between BAG and motion session as well as motion severity, including participant IDs as random effects. We repeated the same analysis using cortical thickness based on FreeSurfer 7.4.1 and to compare the results for volumetric versus surface-based measures of brain morphometry. In contrast with the session with no induced motion, predicted delta age was significantly higher for high motion sessions 2.35 years (t = 5.17, p < 0.0001), with marginal effect for low motion sessions 0.95 years (t = 2.11, p = 0.035) for VBM analysis as well as 3.46 years (t = 11.45, p < 0.0001) for high motion and 2.28 years (t = 7.54, p < 0.0001) for low motion based on cortical thickness. In addition, delta age was significantly associated with motion severity as evaluated by visual rating 0.45 years per rating level (t = 4.59, p < 0.0001) for VBM analysis and 0.83 years per motion level (t = 12.89, p < 0.0001) for cortical thickness analysis. Motion in the scanner can significantly impact brain age estimates, and needs to be accounted for as a confound, particularly when studying populations that are known to have higher levels of motion in the scanner. These results have significant implications for brain age studies in aging and neurodegeneration. Based on these findings, we recommend assessment and inclusion of visual motion ratings in such studies. In cases that the visual rating proves prohibitive, we recommend the inclusion of normalized Euler number from FreeSurfer as defined in the manuscript as a covariate in the models.