Prediction of cognitive performance differences in older age from multimodal neuroimaging data.

Differences in brain structure and functional and structural network architecture have been found to partly explain cognitive performance differences in older ages. Thus, they may serve as potential markers for these differences. Initial unimodal studies, however, have reported mixed prediction results of selective cognitive variables based on these brain features using machine learning (ML). Thus, the aim of the current study was to investigate the general validity of cognitive performance prediction from imaging data in healthy older adults. In particular, the focus was with examining whether (1) multimodal information, i.e., region-wise grey matter volume (GMV), resting-state functional connectivity (RSFC), and structural connectivity (SC) estimates, may improve predictability of cognitive targets, (2) predictability differences arise for global cognition and distinct cognitive profiles, and (3) results generalize across different ML approaches in 594 healthy older adults (age range: 55-85 years) from the 1000BRAINS study. Prediction potential was examined for each modality and all multimodal combinations, with and without confound (i.e., age, education, and sex) regression across different analytic options, i.e., variations in algorithms, feature sets, and multimodal approaches (i.e., concatenation vs. stacking). Results showed that prediction performance differed considerably between deconfounding strategies. In the absence of demographic confounder control, successful prediction of cognitive performance could be observed across analytic choices. Combination of different modalities tended to marginally improve predictability of cognitive performance compared to single modalities. Importantly, all previously described effects vanished in the strict confounder control condition. Despite a small trend for a multimodal benefit, developing a biomarker for cognitive aging remains challenging.

Classification and prediction of cognitive performance differences in older age based on brain network patterns using a machine learning approach.

Age-related cognitive decline varies greatly in healthy older adults, which may partly be explained by differences in the functional architecture of brain networks. Resting-state functional connectivity (RSFC) derived network parameters as widely used markers describing this architecture have even been successfully used to support diagnosis of neurodegenerative diseases. The current study aimed at examining whether these parameters may also be useful in classifying and predicting cognitive performance differences in the normally aging brain by using machine learning (ML). Classifiability and predictability of global and domain-specific cognitive performance differences from nodal and network-level RSFC strength measures were examined in healthy older adults from the 1000BRAINS study (age range: 55-85 years). ML performance was systematically evaluated across different analytic choices in a robust cross-validation scheme. Across these analyses, classification performance did not exceed 60% accuracy for global and domain-specific cognition. Prediction performance was equally low with high mean absolute errors (MAEs ≥ 0.75) and low to none explained variance (R2 ≤ 0.07) for different cognitive targets, feature sets, and pipeline configurations. Current results highlight limited potential of functional network parameters to serve as sole biomarker for cognitive aging and emphasize that predicting cognition from functional network patterns may be challenging.