Fluid Cognition and Functional Connectivity Relate to Cortical Iron in a Depth-Specific Manner in Healthy Aging

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

Jenna Merenstein¹ (jenna.merenstein@duke.edu), Jiayi Zhao¹, David Madden^1,2,3; ¹Brain Imaging and Analysis Center, Duke University Medical Center, Durham, NC 27710, USA, ²Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA, ³Center for Cognitive Neuroscience, Duke University, Durham, NC 27708, USA

Age-related differences in fluid (speed-dependent) cognition, for healthy individuals, have been associated with elevated iron in deep gray matter nuclei, assessed by quantitative susceptibility mapping (QSM), as well as with the merging of functional brain networks, defined from resting-state functional MRI. These age-related differences in iron accumulation and functional connectivity may overlap, particularly in cortical regions, but the few QSM studies assessing cortical iron have used macroscopic approaches that cannot resolve depth-specific differences in iron content. Because cognitive decline in healthy aging is dominated by the slowing of response-related processes, as compared to decision-related processes, the effects of iron content may be more prominent in deeper depths responsible for output functions, as compared to superficial depths responsible for integrating information from other brain regions. Here, using an adult lifespan sample (N = 136; ages 18-80 years), we estimated depth-wise measures of cortical iron, using column-based QSM analyses, and resting-state functional connectivity, using the graph theoretical measure of system segregation. We assessed the relation of cortical iron, at specific depths, to age, functional connectivity, and fluid cognition (tests of memory, executive function, and perceptual-motor speed). Results indicated that higher iron content in deeper, but not superficial, depths was significantly associated with (1) increased age, (2) lower functional connectivity, and (3) worse cognitive performance for adults ages 50+ years. These results suggest that iron content in deeper cortical depths may uniquely contribute to age-related differences in cognition and brain function and may potentially serve as a biomarker of neurodegenerative disease.

Topic Area: METHODS: Neuroimaging