Purpose

To quantitatively asses the iron deposition of the gray nucleus using quantitative susceptibility mapping (QSM), and to analyze the correlation between magnetic sensitivity value (MSV) and cognitive scores in patients with Alzheimer's disease (AD).

Materials and Methods

Fifty-nine patients (21 males, 38 females) with clinically confirmed AD (AD group) and 22 control subjects (12 males, 10 females; CON group) were recruited. Ethical approval and consent forms were obtained. All patients underwent Mini-mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clock Drawing Task (CDT) and Activity of Daily Living (ADL) Scale test, as well as a routine MRI and enhanced gradient echo T2 star weighted angiography (ESWAN).QSM maps were obtained using signal processing in nuclear magnetic resonance (SPIN) (MR Innovations Inc., Detroit, MI, USA, Ver:1.4.5), and magnetic sensitivity value (MSV) of extrapyramidal system were measured, including: head of Caudate Nucleus (HCN), Globus Pallidus (GP), Putamen (PUT), Thalamus (THA), Red Nucleus (RN), Substantia Nigra (SN), Dentate nucleus (DN), gyri fascicular (GF).
Data analyses were performed using statistical package for social science (SPSS) version 20.0 and R version 3.5.3. Independent-samples t-test (for normally distributed data) or Mann–Whitney U test (for non-normally distributed data) was used to compare the MSV between AD group and CON group. Spearman correlation analysis was performed on the MSV and the MMSE score, MoCA score, CDT score, ADL score. False discovery rate (FDR) (Benjamini-Hochberg method) was further adopted to correct for multiple comparisons. P<0.05 was considered statistically significant.

Results

The ROIs on the QSM maps are illustrated in Figure 1. The increased MSV in gray nucleus was present in AD group compared to in CON group, and significant differences were observed for bilateral head of caudate nucleus (HCN) (pL=0.043,pR=0.045), bilateral globus pallidus (GP) (pL=0.04,pR=0.011), right thalamus (THA) (p=0.038), right gyri fascicular (GF) (p=0.039) (Figure 2). The correlation analysis results are shown in heat maps in Figure 3. The MSV of bilateral GP (rL=-0.41, pL=0.001; rR=-0.380, pR=0.003), bilateral putamen (PUT) (rL=-0.320, pL=0.013; rR=-0.340, pR=0.008) had a significant negative correlation with the MMSE score, a significant negative correlation between the MSV of bilateral GP (rL=-0.40, pL=0.002; rR=-0.40, pR=0.002), bilateral PUT(rL=-0.39, pL=0.002; rR=-0.43, pR=0.001) and MoCA scores, the MSV of bilateral PUT(rL=-0.32，pL=0.014；rR=-0.34，pR=0.009) had a significant negative correlation with CDT scores.

Discussion and Conclusion

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most prevalent type of dementia in the elderly [1]. Iron is widely and inhomogeneous distributed in gray nuclei and plays an important role in the brain metabolism and biological process. Excessive iron leads to oxidative stress, destroy the structure of mitochondria, cause damage of synaptic function, trigger apoptosis, loss of neurons, and eventually lead to the decline of cognitive function [2]. In this study it was found that the iron deposition of the gray matter nuclei in AD group was generally higher than that in CON group. In addition, the correlation between MSV of gray matter nuclei and cognitive score (MMSE, MoCA, CDT) was further observed, and indicated more iron deposition may worse cognitive level in AD patients. To conclude, increased iron deposition measured by QSM in gray matter nucleus may be associated with cognitive scores in AD patients.

Acknowledgements

No acknowledgement found.