Multimodal MRI prediction of cognitive functioning across the lifespan: separating between-person differences from within-person changes

Konopkina, K.; Buianova, I.; Lal Khakpoor, F.; Pornprasertmanit, S.; Chan, M.; Pat, N.

doi:10.64898/2026.03.15.711457

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bioRxiv · 10.64898/2026.03.15.711457

Multimodal MRI prediction of cognitive functioning across the lifespan: separating between-person differences from within-person changes

Konopkina, K.·Buianova, I.·Lal Khakpoor, F.·Pornprasertmanit, S.·Chan, M.·Pat, N.

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Abstract

Brain MRI shows promise for predicting cognitive functioning, but its utility depends on its capacity to capture stable between-person differences (e.g., patient stratification), longitudinal within-person changes (e.g., prognosis, treatment monitoring), or both. Using longitudinal data from 450 adults (aged 21-90; up to three waves, five years apart) in the Dallas Lifespan Brain Study, we benchmarked five modalities, task fMRI, functional connectivity (FC), structural MRI (sMRI), diffusion-weighted imaging (DWI), and arterial spin labeling (ASL), across 37 phenotypes and their combination. Stacking all MRI modalities into one marker predicted cognitive functioning with the highest accuracy (R{superscript 2}=.51), followed by DWI and FC. Variance decomposition showed MRI markers explained substantial between-person variance (up to 60.3%) but modest within-person changes (up to 17.2%) in cognitive functioning. Commonality analysis revealed most markers, except ASL, overlapped with age-related variance in cognitive functioning. These findings clarify the strengths and limitations of MRI markers for stratifying and monitoring cognitive aging.

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Konopkina, K., Buianova, I., Lal Khakpoor, F., Pornprasertmanit, S., Chan, M., Pat, N.. 2026-03-18. Multimodal MRI prediction of cognitive functioning across the lifespan: separating between-person differences from within-person changes. https://doi.org/10.64898/2026.03.15.711457

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