Striatal iron content is linked to reduced fronto-striatal brain function under working memory load.

Area of Science:

• Neuroscience
• Neuroimaging
• Aging Research

Background:

• Non-heme iron accumulation is implicated in age-related cognitive decline through oxidative stress and inflammation.
• The specific impact of striatal iron on dynamic brain function, particularly during cognitive tasks, remains largely unexplored.

Purpose of the Study:

• To investigate the effect of striatal iron content on the blood-oxygen-level-dependent (BOLD) modulation during working memory tasks.
• To explore the interaction between age and striatal iron on brain function and its association with cognitive performance.

Main Methods:

• 166 healthy adults (aged 20-94) underwent cognitive testing and functional magnetic resonance imaging (fMRI) including n-back tasks.
• R2*-weighted imaging and pseudo-continuous arterial spin labeling (pcASL) were used to measure brain iron and cerebral blood flow.
• A statistical model predicted voxelwise BOLD modulation by age, striatal iron, and their interaction, controlling for covariates.

Main Results:

• A significant age × striatal iron interaction on BOLD modulation was observed in the putamen, caudate, and inferior frontal gyrus.
• Higher iron content was associated with decreased BOLD modulation in response to increasing working memory load, particularly in younger and middle-aged adults.
• Reduced BOLD modulation linked to iron was further associated with poorer executive function in an age-dependent manner.

Conclusions:

• Striatal iron accumulation may influence functional brain activation patterns even before older adulthood.
• Iron's role in altering brain function trajectories suggests it could be an early contributor to functional brain aging.
• These findings highlight the importance of considering iron levels in understanding cognitive aging processes.