# Prefrontal cortex iron content in neurodegeneration and healthy subjects: A systematic review

## TL;DR

This review examines how iron buildup in the prefrontal cortex is linked to cognitive decline in both healthy aging and neurodegenerative diseases, using MRI techniques like QSM.

## Contribution

The study systematically reviews MRI-based evidence of prefrontal cortex iron accumulation and its correlation with cognitive impairment in neurodegeneration and aging.

## Key findings

- Increased prefrontal cortex iron content correlates with cognitive impairment in neurodegenerative diseases.
- Age-related iron accumulation in the dorsolateral, medial, and anterior PFC subregions is associated with reduced dopamine signaling and poorer cognition in healthy aging.
- Quantitative susceptibility mapping (QSM) is identified as a potential biomarker for assessing prefrontal iron accumulation and cognitive changes.

## Abstract

Iron accumulation in the prefrontal cortex (PFC) has been implicated in neurodegeneration and cognitive decline. Magnetic resonance imaging (MRI) enables noninvasive quantification of brain iron content and deposition. This review aimed to summarize the evidence on the MRI‐based assessment of PFC iron accumulation in healthy individuals and patients with neurodegeneration. A systematic preliminary literature review was conducted using the PubMed, Scopus, Web of Science, and Embase databases. MRI techniques for capturing susceptibility changes reflecting iron, such as susceptibility‐weighted imaging (SWI), quantitative susceptibility mapping (QSM), and R2* mapping, were included. Data were extracted, and narrative synthesis was performed. Twelve studies that measured PFC iron levels using MRI in diseases with neurodegeneration (five studies) and healthy subjects (seven studies) were included. In general, studies involving diseases with neurodegeneration have found that increased PFC iron content correlates with cognitive impairment. Aging studies on healthy subjects have reported that age‐related accumulation of PFC iron, particularly in the dorsolateral, medial, and anterior subregions, increases with age, and is associated with reduced dopamine signaling and poorer cognition. MRI techniques, such as QSM, can quantify prefrontal iron accumulation in diseases with neurodegeneration and aging. As imaging biomarkers, increased prefrontal iron levels may contribute to neurodegeneration and cognitive decline. Longitudinal studies combining advanced QSM and other advanced neuroimaging techniques with cognitive assessments may further elucidate the effects of iron dysregulation on PFC function. Thus, our findings highlight the importance of MRI as a sensitive tool for assessing PFC iron content and its potential role in understanding the pathogenesis of neurodegeneration and the effects of aging on the brain.

This systematic review summarizes magnetic resonance imaging (MRI)‐based assessments of prefrontal cortex (PFC) iron accumulation in healthy individuals and patients with neurodegenerative diseases. The review includes 12 studies using techniques such as susceptibility‐weighted imaging (SWI), quantitative susceptibility mapping (QSM), and R2* mapping. Findings indicate that increased PFC iron content correlates with cognitive impairment in neurodegenerative diseases, with QSM identified as a potential biomarker for early cognitive changes and disease progression. In healthy aging, studies show age‐related iron accumulation in PFC subregions, associated with reduced dopamine signaling and poorer cognition. The review highlights MRI's role as a sensitive tool for assessing PFC iron content, emphasizing the need for longitudinal studies combining advanced MRI and cognitive assessments to further understand the effects of iron dysregulation on PFC function.