Intra-individual cognitive variability in neuropsychological assessment: a sign of neural network dysfunction.

Intra-Individual Cognitive Variability (IICV) predicts progression in neurocognitive disorders . Given important clinical applications, we investigated the association between IICV and multiple brain metrics across 17 networks to better understand the brain mechanisms underlying this performance measure. Sixty-three middle-aged and older adults without dementia underwent a neuropsychological battery, resting-state fMRI, and structural MRI scans. In a linear mixed effect model, higher IICV was associated with lower functional connectivity in control C network relative to medial occipital network (the reference). A multivariate partial least squares analysis revealed that lower mean and higher variability were both associated with lower connectivity in sensorimotor and default mode networks, while higher mean and higher variability were associated with lower volume in default mode and limbic networks. This study suggests that IICV signals widespread network dysfunction across multiple brain networks. These brain abnormalities offer new insights into mechanisms of early cognitive dysfunction. Clinical implications are discussed.