Sub-Networks of the Brain R₂ Structural Connectome Integrity Matrix (SCIM) and Older Adult Cognitive and Motor Functioning

Neuroimaging the structural connectome provides a window into the aging brain; however, few studies address the complexities of mapping late-life structural connectivity. We defined white matter connections via a structural connectivity-based atlas and extracted transverse relaxation rates (R₂) forming a structural connectome integrity matrix to neuroimaging data of 1239 participants (age ~ 79 ± 7). Factor analyses revealed four Sub-Networks (SN) characterized by edge integrity as follows: SN-1 involved most frontal nodes, all parietal nodes, and key subcortical (basal ganglia) structures; SN-2 involved most albeit slightly different frontal nodes than SN-1, nearly all temporal and key subcortical (limbic) nodes; SN-3 was primarily characterized by edges involving select parietal and temporal and all occipital nodes; SN-4 was confined to cerebellum, basal ganglia and limbic nodes. A linear mixed-effects regression model containing weighted composite scores representing each Sub-Network and adjusting for relevant confounders demonstrated associations of lower R₂ in SN-1, SN-2, and SN-4 with lower baseline global cognition and lower R₂ in SN-2 and SN-3 with faster declines in global cognition. Sub-Networks were also differentially associated with domain-specific cognitive functions at baseline and over time. Nearly all Sub-Networks negatively associated with global motor function, dexterity and gait speed at baseline, but only SN-1 and SN-4 were associated with change in motor functioning, specifically gait speed, over time. Our approach to the aging structural connectome provides an assessment of its R₂ integrity and underlying sub-networks as related to critical behaviors associated with normal and pathological aging.