Increased Iron Deposition on Brain Quantitative Susceptibility Mapping Correlates with Decreased Cognitive Function in Alzheimer’s Disease

Abstract

The excessive accumulation of iron in deep gray structures is an important pathological characteristic in patients with Alzheimer's disease (AD). Quantitative susceptibility mapping (QSM) is more specific than other imaging-based iron measurement modalities and allows noninvasive assessment of tissue magnetic susceptibility, which has been shown to correlate well with brain iron levels. This study aimed to investigate the correlations between the magnetic susceptibility values of deep gray matter nuclei and the cognitive functions assessed by mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) in patients with mild and moderate AD. Thirty subjects with mild and moderate AD and 30 age- and sex-matched healthy controls were scanned with a 3.0 T magnetic resonance imaging (MRI) scanner. The magnetic susceptibilities of the regions of interest (ROIs), including caudate nucleus (Cd), putamen (Pt), globus pallidus (Gp), thalamus (Th), red nucleus (Rn), substantia nigra (Sn), and dentate nucleus (Dn), were quantified by QSM. We found that the susceptibility values of the bilateral Cd and Pt were significantly higher in AD patients than the controls ( P < 0.05). In contrast, bilateral Rn had significantly lower susceptibility values in AD than the controls. Regardless of gender and age, the increase of magnetic susceptibility in the left Cd was significantly correlated with the decrease of MMSE scores and MoCA scores ( P < 0.05). Our study indicated that magnetic susceptibility value of left Cd could be potentially used as a biomarker of disease severity in mild and moderate AD.

Striking while the iron is hot: Iron metabolism and ferroptosis in neurodegeneration

“…In post mortem brains, from AD patients and heathy controls, grey matter positive for amyloid plaques showed higher magnetic susceptibility (consistent with greater iron burden) compared to grey matter free of amyloid plaque (Tiepolt et al, 2018). Longitudinal studies have described that iron burden is associated with a marked increase in the rate of cognitive decline in individuals who scan positive for brain amyloid (Ayton et al, 2017b, van Bergen et al, 2018b, van Bergen et al, 2018a, Du et al, 2018.…”

Treating Alzheimer's disease by targeting iron

“…Higher QSM values, particularly in the hippocampus, are associated with accelerated cognitive decline over 6 years in people with PET‐confirmed Aβ pathology, and along the clinical severity spectrum of AD (Ayton, Fazlollahi, et al, ). In cross‐sectional analysis, the severity of cognitive impairment in people with a clinical diagnosis of AD was associated with QSM (Du et al, ), and T 2 * cortical phase shifts (also sensitive to tissue iron) was associated with cognitive performance in people with subjective memory complaints (van Rooden et al, ) and people with AD (Luo et al, ).…”

Sorting Out the Role of the Sortilin-Related Receptor 1 in Alzheimer’s Disease

“…Iron content is increased in both living [123] and post-mortem [124,125] AD brains relative to controls. Iron dyshomeostasis may also be linked to many of the pathologies observed in AD such as mitochondrial dysfunction, vascular pathologies, changes in energy metabolism, and inflammation (reviewed in [122]).…”