Imagine you’re trying to strengthen a muscle by lifting weights. You work hard, but when you check the mirror, you see that your muscle hasn’t grown at all! That’s what researchers found when they investigated cortical thickness changes in patients with mild cognitive impairment (MCI) after computerized working memory (WM) training. In previous studies, healthy individuals showed favorable effects on cortical thickness after WM training. However, this study found no significant structural cortical changes in MCI patients, regardless of the type of training. It suggests that these patients may not experience improved cortical thickness or atrophy during the follow-up period. Interestingly, individuals with the LMX1A-AA genotype showed increased cortical thickness trajectories compared to those with LMX1A-GG/GA after WM training, indicating greater brain plasticity. To confirm these results and explore potential treatments for MCI patients, further trials are needed.

BackgroundAdaptive computerized working memory (WM) training has shown favorable effects on cerebral cortical thickness as compared to non-adaptive training in healthy individuals. However, knowledge of WM training-related morphological changes in mild cognitive impairment (MCI) is limited.ObjectiveThe primary objective of this double-blind randomized study was to investigate differences in longitudinal cortical thickness trajectories after adaptive and non-adaptive WM training in patients with MCI. We also investigated the genotype effects on cortical thickness trajectories after WM training combining these two training groups using longitudinal structural magnetic resonance imaging (MRI) analysis in Freesurfer.MethodMagnetic resonance imaging acquisition at 1.5 T were performed at baseline, and after four- and 16-weeks post training. A total of 81 individuals with MCI accepted invitations to undergo 25 training sessions over 5 weeks. Longitudinal Linear Mixed effect models investigated the effect of adaptive vs. non-adaptive WM training. The LME model was fitted for each location (vertex). On all statistical analyzes, a threshold was applied to yield an expected false discovery rate (FDR) of 5%. A secondary LME model investigated the effects of LMX1A and APOE-ε4 on cortical thickness trajectories after WM training.ResultsA total of 62 participants/patients completed the 25 training sessions. Structural MRI showed no group difference between the two training regimes in our MCI patients, contrary to previous reports in cognitively healthy adults. No significant structural cortical changes were found after training, regardless of training type, across all participants. However, LMX1A-AA carriers displayed increased cortical thickness trajectories or lack of decrease in two regions post-training compared to those with LMX1A-GG/GA. No training or training type effects were found in relation to the APOE-ε4 gene variants.ConclusionThe MCI patients in our study, did not have improved cortical thickness after WM training with either adaptive or non-adaptive training. These results were derived from a heterogeneous population of MCI participants. The lack of changes in the cortical thickness trajectory after WM training may also suggest the lack of atrophy during this follow-up period. Our promising results of increased cortical thickness trajectory, suggesting greater neuroplasticity, in those with LMX1A-AA genotype need to be validated in future trials.

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