Cortical iron mediates age‐related decline in fluid cognition

Abstract

Brain iron dyshomeostasis disrupts various critical cellular functions, and age-related iron accumulation may contribute to deficient neurotransmission and cell death.While recent studies have linked excessive brain iron to cognitive function in the context of neurodegenerative disease, little is known regarding the role of brain iron accumulation in cognitive aging in healthy adults. Further, previous studies have focused primarily on deep gray matter regions, where the level of iron deposition is highest. However, recent evidence suggests that cortical iron may also contribute to cognitive deficit and neurodegenerative disease. Here, we used quantitative susceptibility mapping (QSM) to measure brain iron in 67 healthy participants 18-78 years of age. Speed-dependent (fluid) cognition was assessed from a battery of 12 psychometric and computer-based tests. From voxelwise QSM analyses, we found that QSM susceptibility values were negatively associated with fluid cognition in the right inferior temporal gyrus, bilateral putamen, posterior cingulate gyrus, motor, and premotor cortices. Mediation analysis indicated that susceptibility in the right inferior temporal gyrus was a significant mediator of the relation between age and fluid cognition, and similar effects were evident for the left inferior temporal gyrus at a lower statistical threshold. Additionally, age and right inferior temporal gyrus susceptibility interacted to predict fluid cognition, such that brain iron was negatively associated with a cognitive decline for adults over 45 years of age. These findings suggest that iron may have a mediating role in cognitive decline and may be an early biomarker of neurodegenerative disease.

Cognition and brain iron deposition in whole grey matter regions and hippocampal subfields

“…Our finding that only iron in the putamen increases with age is consistent with other similar studies, while some studies looking at iron deposition in cognitively healthy participants also found increases in iron with age in other regions, particularly in the caudate and hippocampus (Howard et al, 2020; Rodrigue et al, 2020; van Bergen et al, 2018; Venkatesh et al, 2021; Zachariou et al, 2021). The observed decrease in iron in the pallidum and thalamus with age is not consistent with other studies where iron in these regions either increases with age or shows no association with age (Spence et al, 2020; Venkatesh et al, 2021).…”

Age-related differences in frontoparietal activation for target and distractor singletons during visual search

“…The cognitive battery included a total of 12 computerized RT and standardized psychometric tests, with four tests administered for each of three domains of fluid cognition: perceptual-motor speed, executive function, and episodic memory (Howard et al, 2022;Madden, Jain, et al, 2020;. Each domain included one test from the cognition section of the National Institutes of Health (NIH) Toolbox (Gershon et al, 2013).…”

The Advanced BRain Imaging on ageing and Memory (ABRIM) data collection: Study protocol and rationale

“…Second, quantitative imaging techniques are scarcely available in large population studies [24, 26, 31]. Quantitative imaging is particularly useful to investigate myelination and iron depositions in the brain [33–35], and has been associated with cognitive performance in normal aging [13, 36]. Our neuroimaging protocol therefore not only matches the sequences of the aforementioned datasets (i.e., conventional structural T1- and T2-weighted imaging, multi-shell diffusion weighted imaging, and resting-state functional MRI), but also facilitates quantitative imaging with Magnetization Prepared 2 RApid Gradient Echoes (MP2RAGE) and Multi Echo Gradient Echo Imaging (MEGRE) sequences.…”