TY - JOUR T1 - Quantifying age-related changes in brain and behavior: A longitudinal versus cross-sectional approach JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0273-21.2021 SP - ENEURO.0273-21.2021 AU - Georgette Argiris AU - Yaakov Stern AU - Christian Habeck Y1 - 2021/07/19 UR - http://www.eneuro.org/content/early/2021/07/19/ENEURO.0273-21.2021.abstract N2 - Cross-sectional versus longitudinal comparisons of age-related change have often revealed differing results. In the current study, we employed within-subject task-based fMRI to investigate changes in voxel-based activations and behavioral performance across the lifespan in the Reference Ability Neural Network (RANN) cohort, at both baseline and 5-year follow-up. We analyzed fMRI data from between 127 and 159 participants (20-80 years), on a battery of tests relating to each of four cognitive reference abilities (RAs). We applied a Gaussian age kernel to capture continuous change across the lifespan using a 5-year sliding window centered on each age in our participant sample, with a subsequent division into young, middle, and old age brackets. This method was applied separately to both cross-sectional approximations of change and real longitudinal changes adopting a comparative approach. We then focused on longitudinal measurements of neural change to identify regions expressing peak changes and fluctuations of sign change across our sample. Our results revealed several regions expressing divergence between cross-sectional and longitudinal measurements in each domain and age bracket; behavioral comparisons between measurements showed differences in change curves for all four domains, with processing speed displaying the steepest declines. In the longitudinal change measurement, we found lack of support for age-related frontal increases across analyses types, instead finding more posterior regions displaying peak increases in activation, particularly in the old age bracket. Our findings encourage greater focus on longitudinal measurements of age-related changes, which display appreciable differences from cross-sectional approximations.Significance StatementKnowledge of the aging process is mostly informed by cross-sectional studies. The fewer studies that have looked at longitudinal aging trajectories display variable consensus with cross-sectional findings. The current study provides a direct comparison between cross-sectional and longitudinal measurements of change in both neural activation and behavioral performance across several cognitive domains, providing insight into similarities versus discrepancies. Furthermore, it adopts a method of analysis used in the MRI 4D atlas literature to quantify continuous change across the lifespan through construction of neural activation “templates” that are generated from age-weighted averaging across the entire sample. Longitudinal measurements of change could then further be probed for characteristics such as peaks and change fluctuations, enabling a better understanding of true age-related changes. ER -