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Ting Gao

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YNIMG Journal 2022 Journal Article

Altered brain iron depositions from aging to Parkinson's disease and Alzheimer's disease: A quantitative susceptibility mapping study

  • Xiaojun Guan
  • Tao Guo
  • Cheng Zhou
  • Jingjing Wu
  • Qingze Zeng
  • Kaicheng Li
  • Xiao Luo
  • Xueqin Bai

Brain iron deposition is a promising marker for human brain health, providing insightful information for understanding aging as well as neurodegenerations, e. g. , Parkinson's disease (PD) and Alzheimer's disease (AD). To comprehensively evaluate brain iron deposition along with aging, PD-related neurodegeneration, from prodromal PD (pPD) to clinical PD (cPD), and AD-related neurodegeneration, from mild cognitive impairment (MCI) to AD, a total of 726 participants from July 2013 to December 2020, including 100 young adults, 189 old adults, 184 pPD, 171 cPD, 31 MCI and 51 AD patients, were included. Quantitative susceptibility mapping data were acquired and used to quantify regional magnetic susceptibility, and the resulting spatial standard deviations were recorded. A general linear model was applied to perform the inter-group comparison. As a result, relative to young adults, old adults showed significantly higher iron deposition with higher spatial variation in all of the subcortical nuclei (p < 0. 01). pPD showed a high spatial variation of iron distribution in the subcortical nuclei except for substantia nigra (SN); and iron deposition in SN and red nucleus (RN) were progressively increased from pPD to cPD (p < 0. 01). AD showed significantly higher iron deposition in caudate and putamen with higher spatial variation compared with old adults, pPD and cPD (p < 0. 01), and significant iron deposition in SN compared with old adults (p < 0. 01). Also, linear regression models had significances in predicting motor score in pPD and cPD (Rmean = 0. 443, Ppermutation = 0. 001) and cognition score in MCI and AD (Rmean = 0. 243, Ppermutation = 0. 037). In conclusion, progressive iron deposition in the SN and RN may characterize PD-related neurodegeneration, namely aging to cPD through pPD. On the other hand, extreme iron deposition in the caudate and putamen may characterize AD-related neurodegeneration.

YNICL Journal 2021 Journal Article

Locus coeruleus degeneration is associated with disorganized functional topology in Parkinson’s disease

  • Cheng Zhou
  • Tao Guo
  • Xueqin Bai
  • Jingjing Wu
  • Ting Gao
  • Xiaojun Guan
  • Xiaocao Liu
  • Luyan Gu

Degeneration of the locus coeruleus (LC) is recognized as a critical hallmark of Parkinson's disease (PD). Recent studies have reported that noradrenaline produced from the LC has critical effects on brain functional organization. However, it is unknown if LC degeneration in PD contributes to cognitive/motor manifestations through modulating brain functional organization. This study enrolled 94 PD patients and 68 healthy controls, and LC integrity was measured using the contrast-to-noise ratio of the LC (CNRLC) calculated from T1-weighted magnetic resonance imaging. We used graph-theory-based network analysis to characterize brain functional organization. The relationships among LC degeneration, network disruption, and cognitive/motor manifestations in PD were assessed. Whether network disruption was a mediator between LC degeneration and cognitive/motor impairments was assessed further. In addition, an independent PD subgroup (n = 35) having functional magnetic resonance scanning before and after levodopa administration was enrolled to evaluate whether LC degeneration-related network deficiencies were independent of dopamine deficiency. We demonstrated that PD patients have significant LC degeneration compared to healthy controls. CNRLC was positively correlated with Montreal Cognitive Assessment score and the nodal efficiency (NE) of several cognitive-related regions. Lower NE of the superior temporal gyrus was a mediator between LC degeneration and cognitive impairment in PD. However, levodopa treatment could not normalize the reduced NE of the superior temporal gyrus (mediator). In conclusion, we provided evidence for the relationship between LC degeneration and extensive network disruption in PD, and highlight the role of network disorganization in LC degeneration-related cognitive impairment.

YNICL Journal 2020 Journal Article

Fixel-based analysis reveals fiber-specific alterations during the progression of Parkinson’s disease

  • Yanxuan Li
  • Tao Guo
  • Xiaojun Guan
  • Ting Gao
  • Wenshuang Sheng
  • Cheng Zhou
  • Jingjing Wu
  • Min Xuan

Disruption of brain circuits is one of the core mechanisms of Parkinson's disease (PD). Understanding structural connection alterations in PD is important for effective treatment. However, due to methodological limitations, most studies were unable to account for confounding factors such as crossing fibers and were unable to identify damages to specific fiber tracts. In the present study, we aimed to demonstrate tract-specific white matter structural changes in PD patients and their relationship with clinical symptoms. Ninety-eight PD patients, divided into early (ES) and middle stage (MS) groups, and 76 healthy controls (HCs) underwent brain magnetic resonance imaging scans and clinical assessments. Fixel-based analysis was used to investigate fiber tract alterations in PD patients. Compared to HCs, the PD patients showed decreased fiber density (FD) in the corpus callosum (CC), increased FD in the cortical spinal tract (CST), and increased fiber-bundle cross-section (FC, log-transformed: log-FC) in the superior cerebellar peduncle (SCP). Analysis of variance (ANOVA) revealed significant differences in FD in the CST and log-FC in the SCP among the three groups. Post-hoc analysis revealed that the mean FD values of the CST were higher in ES and MS patient groups compared to HCs, and the mean log-FC values of the SCP were higher in ES and MS patient groups compared to HCs. Additionally, the FD values of the CC in PD patients were negatively correlated with the Unified Parkinson's Disease Rating Scale part-III (UPDRS-III) scores (r = -0.257, p = 0.032), Hamilton Depression Rating Scale 17 Items (HAMD-17) scores (r = -0.230, p = 0.033), and Hamilton Anxiety Scale (HAMA) scores (r = -0.248, p = 0.032). Moreover, log-FC values of the SCP (r = 0.274, p = 0.028) and FD values of the CST (r = 0.384, p < 0.001) were positively correlated with the UPDRS-III scores. We concluded that PD patients had both decreased and increased white matter integrity within specific fiber bundles. Additionally, these white matter alterations were different across disease stages, suggesting the occurrence of complex pathological and compensatory changes during the development of PD.

v2026.09.13