Connectome‐based predictive modelling of cognitive reserve using task‐based functional connectivity

Cognitive reserve supports cognitive function in the presence of pathology or atrophy. Functional neuroimaging may enable direct and accurate measurement of cognitive reserve which could have considerable clinical potential. The present study aimed to develop and validate a measure of cognitive reserve using task‐based fMRI data that could then be applied to independent resting‐state data. Connectome‐based predictive modelling with leave‐one‐out cross‐validation was applied to predict a residual measure of cognitive reserve using task‐based functional connectivity from the Cognitive Reserve/Reference Ability Neural Network studies (n = 220, mean age = 51.91 years, SD = 17.04 years). This model generated summary measures of connectivity strength that accurately predicted a residual measure of cognitive reserve in unseen participants. The theoretical validity of these measures was established via a positive correlation with a socio‐behavioural proxy of cognitive reserve (verbal intelligence) and a positive correlation with global cognition, independent of brain structure. This fitted model was then applied to external test data: resting‐state functional connectivity data from The Irish Longitudinal Study on Ageing (TILDA, n = 294, mean age = 68.3 years, SD = 7.18 years). The network‐strength predicted measures were not positively associated with a residual measure of cognitive reserve nor with measures of verbal intelligence and global cognition. The present study demonstrated that task‐based functional connectivity data can be used to generate theoretically valid measures of cognitive reserve. Further work is needed to establish if, and how, measures of cognitive reserve derived from task‐based functional connectivity can be applied to independent resting‐state data. Task‐based fMRI may enable more accurate direct measurement of cognitive reserve (CR) but rs‐fMRI can be more widely used. Connectome‐based predictive modelling was applied to task‐based functional connectivity in a training dataset to predict a CR residual. The task‐based predicted values were validated as measures of CR but the task‐based model did not generalize to resting‐state data in an independent test dataset.