Locus Coeruleus Degeneration Correlated with Levodopa Resistance in Parkinson’s Disease: A Retrospective Analysis

Zhou, Cheng; Guo, Tao; Wu, Jingjing; Wang, Linbo; Bai, Xueqin; Gao, Ting; Guan, Xiaojun; Gu, Luyan; Huang, Peiyu; Xuan, Min; Gu, Quanquan; Xu, Xiaojun; Zhang, Baorong; Cheng, Wei; Feng, Jianfeng; Zhang, Minming

doi:10.3233/jpd-212720

Cited by 10 publications

(10 citation statements)

References 45 publications

(59 reference statements)

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“…We demonstrated a significant relationship between LC degeneration and functional organization of the motor cortex. In addition, we demonstrated a significant relationship between LC degeneration and motor response to levodopa in recent published paper ( Zhou et al, 2021 ). Therefore; the interactions between the dopaminergic and noradrenergic systems require further investigation.…”

Section: Discussionsupporting

confidence: 64%

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

Zhou

Guo

Bai

et al. 2021

NeuroImage: Clinical

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Section: Discussionsupporting

confidence: 64%

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

Zhou

Guo

Bai

et al. 2021

NeuroImage: Clinical

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“…Notably, we found that subtype 1 showed a signi cantly poor response to levodopa replacement therapy than subtype 2, which may suggest the different pathobiological mechanisms. In consistent with this nding, recent animal and human studies have shown that the de ciency of LC-noradrenergic system could complicate PD symptoms and diminishes the therapeutic e cacy of levodopa 33,44 . We also found that subtype 2 showed signi cant damage of perfusion and functional synchronization in cortical regions.…”

Section: Clinical and Neurodegeneration Trajectories Of Twosupporting

confidence: 65%

“…Therefore, we used the NM-MRI to measure the degeneration of SN and LC. According to previous method, we calculated the contrast to noise ratio of the SN (CNR SN ) and LC (CNR LC ), which represented the integrity of SN and LC 33 . A lower CNR value means more serious degeneration.…”

Section: Neuromelanin Sensitive Image Processingmentioning

confidence: 99%

Two distinct trajectories of clinical and neurodegeneration events identified in Parkinson's disease

Zhou

Wang

Cheng

et al. 2022

Preprint

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Background Increasing evidence suggests that Parkinson's disease (PD) may have distinct spatial and temporal progression patterns. We aimed to disentangle the distinct trajectories of clinical and neurodegeneration events of PD by using a novel data-driven Subtype and Stage Inference (SuStaIn) model.Methods We enrolled 201 PD patients and 118 healthy controls with comprehensive olfactory, autonomic function, cognitive, sleep, emotional tests, and multimodality MRI scanning (T1-weighted imaging, diffusion tensor imaging, and neuromelanin-sensitive imaging). The volume and mean diffusivity of cortical/subcortical regions, the signal of substantia nigra (SN) and locus coeruleus (LC) were then obtained. Above features were input into SuStaIn model to identify PD subtypes with distinct progress trajectories. An independent dataset with 151 PD patients and 57 healthy controls was used to validate our findings. Finally, the differences in clinical, imaging, biochemical profiles, levodopa treatment response, and longitudinal prognosis between PD subtypes were assessed. Results We identified two distinct PD subtypes: subtype 1 with rapid eye movement sleep behavior disorder (RBD), autonomic dysfunction, SN and LC degeneration as early manifestations and cognitive impairment, limbic degeneration as advanced manifestation; while subtype 2 with cognitive impairment, SN and limbic degeneration as early manifestation, and RBD, LC degeneration as advanced manifestations. The two subtypes were successfully validated in the independent dataset. In addition, we found that subtype 1 showed poorer levodopa response and longitudinal prognosis when compared with subtype 2.Conclusion We demonstrated two PD subtypes with distinct clinical and neurodegeneration trajectories, which are consistent with the recently proposed “body-first” and “brain-first” hypothesis. Meanwhile, the distinct treatment response and prognosis between two subtypes provided new insights into the underlying disease biology and may be useful for personalized treatment for individuals with different subtypes of PD.

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“…There was an association between regional structural degeneration and individual expressions of PD nonmotor symptoms (such as orthostatic dysregulation or apathy) 43 . Another group found a significant positive correlation between LC NM contrast and the extent of motor improvement after levodopa administration 45 . They concluded that evaluating LC NM parameters using NM‐MRI might be predictive of levodopa responsiveness in PD.…”

Section: Neuromelanin Iron and The N1 Sign In Pdmentioning

confidence: 99%

Application of Neuromelanin MR Imaging in Parkinson Disease

Chen

LeWitt

et al. 2022

Magnetic Resonance Imaging

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MRI has been used to develop biomarkers for movement disorders such as Parkinson disease (PD) and other neurodegenerative disorders with parkinsonism such as progressive supranuclear palsy and multiple system atrophy. One of these imaging biomarkers is neuromelanin (NM), whose integrity can be assessed from its contrast and volume. NM is found mainly in certain brain stem structures, namely, the substantia nigra pars compacta (SNpc), the ventral tegmental area, and the locus coeruleus. Another major biomarker is brain iron, which often increases in concert with NM degeneration. These biomarkers have the potential to improve diagnostic certainty in differentiating between PD and other neurodegenerative disorders similar to PD, as well as provide a better understanding of pathophysiology. Mapping NM in vivo has clinical importance for gauging the premotor phase of PD when there is a greater than 50% loss of dopaminergic SNpc melanized neurons. As a metal ion chelator, NM can absorb iron. When NM is released from neurons, it deposits iron into the intracellular tissues of the SNpc; the result is iron that can be imaged and measured using quantitative susceptibility mapping. An increase of iron also leads to the disappearance of the nigrosome‐1 sign, another neuroimage biomarker for PD. Therefore, mapping NM and iron changes in the SNpc are a practical means for improving early diagnosis of PD and in monitoring disease progression. In this review, we discuss the functions and location of NM, how NM‐MRI is performed, the automatic mapping of NM and iron content, how NM‐related imaging biomarkers can be used to enhance PD diagnosis and differentiate it from other neurodegenerative disorders, and potential advances in NM imaging methods. With major advances currently evolving for rapid imaging and artificial intelligence, NM‐related biomarkers are likely to have increasingly important roles for enhancing diagnostic capabilities in PD. Evidence Level 1 Technical Efficacy Stage 2

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Locus Coeruleus Degeneration Correlated with Levodopa Resistance in Parkinson’s Disease: A Retrospective Analysis

Cited by 10 publications

References 45 publications

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

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

Two distinct trajectories of clinical and neurodegeneration events identified in Parkinson's disease

Application of Neuromelanin MR Imaging in Parkinson Disease

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