Baseline Frontoparietal Gray Matter Volume Predicts Executive Function Performance in Aging and Mild Cognitive Impairment at 24-Month Follow-Up.

Background:Executive dysfunction in mild cognitive impairment (MCI) has been associated with gray matter atrophy. Prior studies have yielded limited insight into associations between gray matter volume and executive function in early and late amnestic MCI (aMCI). Objective:To examine the relative importance of predictors of executive function at 24 months and relationships between baseline regional gray matter volume and executive function performance at 24-month follow-up in non-demented older adults. Methods:147 participants from the Alzheimer's Disease Neuroimaging Initiative (mean age = 70.6 years) completed brain magnetic resonance imaging and neuropsychological testing and were classified as cognitively normal (n = 49), early aMCI (n = 60), or late aMCI (n = 38). Analyses explored the importance of demographic, APOEɛ4, biomarker (p-tau/Aβ42, t-tau/Aβ42), and gray matter regions-of-interest (ROI) variables to 24-month executive function, whether ROIs predicted executive function, and whether relationships varied by baseline diagnostic status. Results:Across all participants, baseline anterior cingulate cortex and superior parietal lobule volumes were the strongest predictors of 24-month executive function performance. In early aMCI, anterior cingulate cortex volume was the strongest predictor and demonstrated a significant interaction such that lower volume related to worse 24-month executive function in early aMCI. Educational attainment and inferior frontal gyrus volume were the strongest predictors of 24-month executive function performance for cognitively normal and late aMCI groups, respectively. Conclusions:Baseline frontoparietal gray matter regions were significant predictors of executive function performance in the context of aMCI and may identify those at risk of Alzheimer's disease. Anterior cingulate cortex volume may predict executive function performance in early aMCI.