Lateral ventricle volume trajectories predict response inhibition in older age-A longitudinal brain imaging and machine learning approach

Objective In a three-wave 6 yrs longitudinal study we investigated if the expansion of lateral ventricle (LV) volumes (regarded as a proxy for brain tissue loss) predicts third wave performance on a test of response inhibition (RI). Participants and methods Trajectories of left and right lateral ventricle volumes across the three waves were quantified using the longitudinal stream in Freesurfer. All participants (N= 74;48 females;mean age 66.0 yrs at the third wave) performed the Color-Word Interference Test (CWIT). Response time on the third condition of CWIT, divided into fast, medium and slow, was used as outcome measure in a machine learning framework. Initially, we performed a linear mixed effect (LME) analysis to describe subject-specific trajectories of the left and right LV volumes (LVV). These features were input to a multinomial logistic regression classification procedure, predicting individual belongings to one of the three RI classes. To obtain results that might generalize, we evaluated the significance of a k-fold cross-validated f1-score with a permutation test, providing a p-value that approximates the probability that the score would be obtained by chance. We also calculated a corresponding confusion matrix. Results The LME-model showed an annual similar to 3.0% LVV increase. Evaluation of a cross-validated score using 500 permutations gave an f1-score of 0.462 that was above chance level (p = 0.014). 56% of the fast performers were successfully classified. All these were females, and typically older than 65 yrs at inclusion. For the true slow performers, those being correctly classified had higher LVVs than those being misclassified, and their ages at inclusion were also higher. Conclusion Major contributions were: (i) a longitudinal design, (ii) advanced brain imaging and segmentation procedures with longitudinal data analysis, and (iii) a data driven machine learning approach including cross-validation and permutation testing to predict behaviour, solely from the individual's brain signatures (LVV trajectories).