Predicting future cognitive decline from non-brain and multimodal brain imaging data in healthy and pathological aging

Cognitive decline occurs in healthy and pathological aging, and both may be preceded by subtle changes in the brain -- offering a basis for cognitive predictions. Previous work has largely focused on predicting a diagnostic label from structural brain imaging. Our study broadens the scope of applications to cognitive decline in healthy aging by predicting future decline as a continuous trajectory, rather than a diagnostic label. Furthermore, since brain structure as well as function changes in aging, it is reasonable to expect predictive gains when using multiple brain imaging modalities. Here, we tested whether baseline multimodal neuroimaging data improve the prediction of future cognitive decline in healthy and pathological aging. Non-brain data (including demographics and clinical and neuropsychological scores) were combined with structural and functional connectivity MRI data from the OASIS-3 project (N = 662; age = 46 - 96y). The combined input data was entered into cross-validated multi-target random forest models to predict future cognitive decline (measured by the Clinical Dementia Rating and the Mini-Mental State Examination), on average 5.8y into the future. The analysis was preregistered and all analysis code is publicly available. We found that combining non-brain with structural data improved the continuous prediction of future cognitive decline (best test-set performance: R2 = 0.42) and that cognitive performance, daily functioning, and subcortical volume drove the performance of our model. In contrast, including functional connectivity did not improve predictive accuracy. In the future, the prognosis of age-related cognitive decline may enable earlier and more effective cognitive, pharmacological, and behavioral interventions to be tailored to the individual.