Pat, N. | Search bioRxiv

bioRxiv2023

The (Limited?) Utility of Brain Age as a Biomarker for Capturing Cognitive Decline

Fluid cognition usually declines as people grow older. For decades, neuroscientists have been on a quest to search for a biomarker that can help capture fluid cognition. One well-known candidate is Brain Age, or a predicted value based on machine-learning models built to predict chronological age from brain MRI data. Here we aim to formally evaluate the utility of Brain Age as a biomarker for capturing fluid cognition among older individuals. Using 504 aging participants (36-100 years old) from the Human Connectome Project in Aging, we created 26 age-prediction models for Brain Age based on different combinations of MRI modalities. We first tested how much Brain Age from these age-prediction models added to what we had already known from a persons chronological age in capturing fluid cognition. Based on the commonality analyses, we found a large degree of overlap between Brain Age and chronological age, so much so that, at best, Brain Age could uniquely add only around 1.6% in explaining variation in fluid cognition. Next, the age-prediction models that performed better at predicting chronological age did NOT necessarily create better Brain Age for capturing fluid cognition over and above chronological age. Instead, better-performing age-prediction models created Brain Age that overlapped larger with chronological age, up to around 29% out of 32%, in explaining fluid cognition, thus not improving the models utility to capture cognitive abilities. Lastly, we tested how much Brain Age missed the variation in the brain MRI that could explain fluid cognition. To capture this variation in the brain MRI that explained fluid cognition, we computed Brain Cognition, or a predicted value based on prediction models built to directly predict fluid cognition (as opposed to chronological age) from brain MRI data. We found that Brain Cognition captured up to an additional 11% of the total variation in fluid cognition that was missing from the model with only Brain Age and chronological age, leading to around a 1/3-time improvement of the total variation explained. Accordingly, we demonstrated the limited utility of Brain Age as a biomarker for fluid cognition and made some suggestions to ensure the utility of Brain Age in explaining fluid cognition and other phenotypes of interest.

neuroscience↗

bioRxiv2021

Integrating Task-Based Functional MRI Across Tasks Markedly Boosts Prediction and Reliability of Brain-Cognition Relationship

Capturing individual differences in cognition is central to human neuroscience. Yet our ability to estimate cognitive abilities via brain MRI is still poor in both prediction and reliability. Our study tested if this inability can be improved by integrating MRI signals across the whole brain and across modalities, including task-based functional MRI (tfMRI) of different tasks along with other non-task MRI modalities, such as structural MRI, resting-state functional connectivity. Using the Human Connectome Project (n=873, 473 females, after quality control), we directly compared predictive models comprising different sets of MRI modalities (e.g., seven tasks vs. non-task modalities). We applied two approaches to integrate multimodal MRI, stacked vs. flat models, and implemented 16 combinations of machine-learning algorithms. The stacked model integrating all modalities via stacking Elastic Net provided the best prediction (r=.57), relatively to other models tested, as well as excellent test-retest reliability (ICC=~.85) in capturing general cognitive abilities. Importantly, compared to the stacked model integrating across non-task modalities (r=.27), the stacked model integrating tfMRI across tasks led to significantly higher prediction (r=.56) while still providing excellent test-retest reliability (ICC=~.83). The stacked model integrating tfMRI across tasks was driven by frontal and parietal areas and by tasks that are cognition-related (working-memory, relational processing, and language). This result is consistent with the parieto-frontal integration theory of intelligence. Accordingly, our results contradict the recently popular notion that tfMRI is not reliable enough to capture individual differences in cognition. Instead, our study suggests that tfMRI, when used appropriately (i.e., by drawing information across the whole brain and across tasks and by integrating with other modalities), provides predictive and reliable sources of information for individual differences in cognitive abilities, more so than non-task modalities. HighlightsO_LINon-task MRI (sMRI, rs-fMRI) are often used for the brain-cognition relationship. C_LIO_LITask-based fMRI has been deemed unreliable for capturing individual differences. C_LIO_LIWe tested if drawing task-based fMRI information across regions/tasks improves prediction and reliability of the brain-cognition relationship. C_LIO_LIOur approach boosts prediction of task-based fMRI over non-task MRI. C_LIO_LIOur approach renders task-based fMRI reliable over time. C_LIO_LIOur approach shows the importance of the fronto-parietal areas in cognition. C_LI

neuroscience↗