Background: Hand dexterity is affected by normal aging and neuroinflammatory processes in the brain. Understanding the relationship between hand dexterity and brain structure in neurotypical older adults may be informative about prodromal pathological processes, thus providing an opportunity for earlier diagnosis and intervention to improve functional outcomes. Methods: this study investigates the associations between hand dexterity and brain measures in neurotypical older adults (≥65 years) using the Nine-Hole Peg Test (9HPT) and magnetic resonance imaging (MRI). Results: Elastic net regularized regression revealed that reduced hand dexterity in dominant and non-dominant hands was associated with an enlarged volume of the left choroid plexus, the region implicated in neuroinflammatory and altered myelination processes, and reduced myelin content in the left frontal operculum, the region implicated in motor imagery, action production, and higher-order motor functions. Distinct neural mechanisms underlying hand dexterity in dominant and non-dominant hands included the differences in caudate and thalamic volumes as well as altered cortical myelin patterns in frontal, temporal, parietal, and occipital regions supporting sensorimotor and visual processing and integration, attentional control, and eye movements. Although elastic net identified more predictive features for the dominant vs. non-dominant hand, the feature stability was higher for the latter, thus indicating higher generalizability for the non-dominant hand model. Conclusions: Our findings suggest that the 9HPT for hand dexterity might be a cost-effective screening tool for early detection of neuroinflammatory and neurodegenerative processes. Longitudinal studies are needed to validate our findings in a larger sample and explore the potential of hand dexterity as an early clinical marker.
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