Longitudinal iron accumulation in caudate related to changes in frontoparietal control network connectivity and planning ability in older adults

Poster Session C - Sunday, April 14, 2024, 5:00 – 7:00 pm EDT, Sheraton Hall ABC

Jing Zhou¹, Colleen Hughes¹, Alfie Wearn¹, Julia Huck², Giulia Baracchini¹, Elisabeth Sylvain³, Jennifer Tremblay-Mercier³, Judes Poirier⁴, Sylvia Villeneuve⁴, Christine Lucas Tardif¹, Claudine J. Gauthier², Gary R. Turner⁵, R. Nathan Spreng¹; ¹Montreal Neurological Institute, McGill University Montreal, QC, Canada, ²Physics Department, Concordia University, Montréal, QC, Concordia University, Montreal, QC, Canada, ³StoP-AD Centre, Douglas Mental Health Institute Research Centre, Montreal, QC, Canada, ⁴Department of Psychiatry, McGill University, Montreal, QC, Canada, ⁵Department of Psychology, York University, Toronto, ON, Canada

Cognitive functions attributed to the frontoparietal control network (FPCN) are central to goal-directed behaviors, and these abilities are vulnerable to decline with advancing age. Age-related declines in executive function (EF) have been linked to dopaminergic striatal dysfunction. Elevated striatal iron deposition has been associated with lower cognition, and differences in brain function. 132 older adults at familial risk for AD from PREVENT-AD cohort underwent MRI scanning at baseline and follow-up (mean interval, 2.7y). 81 completed the CBS test battery (Planning, Token Search); 127 completed the TMT and Stroop at each timepoint. QSM maps were reconstructed from a 3D single-echo GRE sequence and QSM value in caudate was then calculated. Multi-echo resting state functional connectivity (RSFC) matrices were initialized to the 200-parcel Schaefer atlas for each participant. Correlation between parcels in FPCN was computed for each timepoint, resulting in 2 X RSFC matrices. Here, we examined the impact of longitudinal iron accumulation in caudate, a core subcortical node of the FPCN, on RSFC changes in the FPCN using behavioral Partial Least Squares, and then examined impact of this multivariate association on changes in EF using linear mixed model. We found that increasing iron content in caudate was significantly associated with longitudinal FPCN RSFC (p<.05). Caudate iron - FPCN longitudinal effects were associated with decline in planning ability (r =.67, p<.005) but not other measures of EF. These findings suggest that iron accumulation may be a driving pathological factor in RSFC changes, and predicts changes in planning ability with advancing age.

Topic Area: METHODS: Neuroimaging