Depthwise cortical iron relates to functional connectivity and fluid cognition in healthy aging.
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2025-04
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Abstract
Age-related differences in fluid cognition have been associated with both the merging of functional brain networks, defined from resting-state functional magnetic resonance imaging (rsfMRI), and with elevated cortical iron, assessed by quantitative susceptibility mapping (QSM). Limited information is available, however, regarding the depthwise profile of cortical iron and its potential relation to functional connectivity. Here, using an adult lifespan sample (n = 138; 18-80 years), we assessed relations among graph theoretical measures of functional connectivity, column-based depthwise measures of cortical iron, and fluid cognition (i.e., tests of memory, perceptual-motor speed, executive function). Increased age was related both to less segregated functional networks and to increased cortical iron, especially for superficial depths. Functional network segregation mediated age-related differences in memory, whereas depthwise iron mediated age-related differences in general fluid cognition. Lastly, higher mean parietal iron predicted lower network segregation for adults younger than 45 years of age. These findings suggest that functional connectivity and depthwise cortical iron have distinct, complementary roles in the relation between age and fluid cognition in healthy adults.
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Merenstein, Jenna L, Jiayi Zhao and David J Madden (2025). Depthwise cortical iron relates to functional connectivity and fluid cognition in healthy aging. Neurobiology of aging, 148. pp. 27–40. 10.1016/j.neurobiolaging.2025.01.006 Retrieved from https://hdl.handle.net/10161/32164.
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Jenna Merenstein
My research uses MRI to study the effect of healthy brain aging on numerous cognitive abilities, especially memory and attention. I also use MRI to study the structural and functional brain properties that differentiate Alzheimer's disease from healthy aging. I obtained my Ph.D. in Cognitive Neuroscience in April 2022 from Dr. Lani Bennett's lab at the University of California, Riverside. I am currently a Postdoctoral Associate working in the Brain Imaging and Analysis Center (BIAC) with Dr. David Madden.
David Joseph Madden
My research focuses primarily on the cognitive neuroscience of aging: the investigation of age-related changes in perception, attention, and memory, using both behavioral measures and neuroimaging techniques, including positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI).
The behavioral measures have focused on reaction time, with the goal of distinguishing age-related changes in specific cognitive abilities from more general effects arising from a slowing in elementary perceptual processes. The cognitive abilities of interest include selective attention as measured in visual search tasks, semantic and episodic memory retrieval, and executive control processes.
The behavioral measures are necessary to define the cognitive abilities of interest, and the neuroimaging techniques help define the functional neuroanatomy of those abilities. The PET and fMRI measures provide information regarding neural activity during cognitive performance. DTI is a recently developed technique that images the structural integrity of white matter. The white matter tracts of the brain provide critical pathways linking the gray matter regions, and thus this work will complement the studies using PET and fMRI that focus on gray matter activation.
A current focus of the research program is the functional connectivity among regions, not only during cognitive task performance but also during rest. These latter measures, referred to as intrinsic functional connectivity, are beginning to show promise as an index of overall brain functional efficiency, which can be assessed without the implementation of a specific cognitive task. From DTI, information can be obtained regarding how anatomical connectivity constrains intrinsic functional connectivity. It will be important to determine the relative influence of white matter pathway integrity, intrinsic functional connectivity, and task-related functional connectivity, as mediators of age-related differences in behavioral measures of cognitive performance.
Ultimately, the research program can help link age-related changes in cognitive performance to changes in the structure and function of specific neural systems. The results also have implications for clinical translation, in terms of the identification of neural biomarkers for the diagnosis of neural pathology and targeting rehabilitation procedures.
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