Junjiao Zhang's research while affiliated with Beijing Tiantan Hospital and other places

Background Iron deposition plays a crucial role in the pathophysiology of Parkinson’s disease (PD), yet the distribution pattern of iron deposition in the subcortical nuclei has been inconsistent across previous studies. We aimed to assess the difference patterns of iron deposition detected by quantitative iron-sensitive magnetic resonance imaging (MRI) between patients with PD and patients with atypical parkinsonian syndromes (APSs), and between patients with PD and healthy controls (HCs). Methods A systematic literature search was conducted on PubMed, Embase, and Web of Science databases to identify studies investigating the iron content in PD patients using the iron-sensitive MRI techniques (R2 * and quantitative susceptibility mapping [QSM]), up until May 1, 2023. The quality assessment of case-control and cohort studies was performed using the Newcastle-Ottawa Scale, whereas diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Standardized mean differences and summary estimates of sensitivity, specificity, and area under the curve (AUC) were calculated for iron content, using a random effects model. We also conducted the subgroup-analysis based on the MRI sequence and meta-regression. Results Seventy-seven studies with 3192 PD, 209 multiple system atrophy (MSA), 174 progressive supranuclear palsy (PSP), and 2447 HCs were included. Elevated iron content in substantia nigra (SN) pars reticulata ( P <0.001) and compacta ( P <0.001), SN ( P <0.001), red nucleus (RN, P <0.001), globus pallidus ( P <0.001), putamen (PUT, P = 0.009), and thalamus ( P = 0.046) were found in PD patients compared with HCs. PD patients showed lower iron content in PUT ( P <0.001), RN ( P = 0.003), SN ( P = 0.017), and caudate nucleus ( P = 0.027) than MSA patients, and lower iron content in RN ( P = 0.001), PUT ( P <0.001), globus pallidus ( P = 0.004), SN ( P = 0.015), and caudate nucleus ( P = 0.001) than PSP patients. The highest diagnostic accuracy distinguishing PD from HCs was observed in SN (AUC: 0.85), and that distinguishing PD from MSA was found in PUT (AUC: 0.90). In addition, the best diagnostic performance was achieved in the RN for distinguishing PD from PSP (AUC: 0.84). Conclusion Quantitative iron-sensitive MRI could quantitatively detect the iron content of subcortical nuclei in PD and APSs, while it may be insufficient to accurately diagnose PD. Future studies are needed to explore the role of multimodal MRI in the diagnosis of PD. Registrision PROSPERO; CRD42022344413.

Aims Parkinsonian tremor (PT) is regulated by numerous neurophysiological components across multiple temporospatial scales. The dynamics of tremor fluctuation are thus highly complex. This study aimed to explore the effects of different medications on tremor complexity, and how the underlying factors contribute to such tremor complexity. Methods In this study, 66 participants received a 2‐mg dose of benzhexol or a pre‐determined dose of levodopa at two study visits in a randomized order. Before and after taking the medications, tremor fluctuation was recorded using surface electromyography electrodes and accelerometers in resting, posture, and weighting conditions with and without a concurrent cognitive task. Tremor complexity was quantified using multiscale entropy. Results Tremor complexity in resting (p = 0.002) and postural condition (p < 0.0001) was lower when participants were performing a cognitive task compared to a task‐free condition. After taking levodopa and benzhexol, participants had increased (p = 0.02–0.03) and decreased (p = 0.03) tremor complexity compared to pre‐medication state, respectively. Tremor complexity and its changes as induced by medications were significantly correlated with clinical ratings and their changes (β = −0.23 to −0.39; p = 0.002–0.04), respectively. Conclusion Tremor complexity may be a promising marker to capture the pathophysiology underlying the development of PT, aiding the characterization of the effects medications have on PT regulation.

Background Pathological tau accumulates in the cerebral cortex of Parkinson's disease (PD), resulting in cognitive deterioration. Positron emission tomography (PET) can be used for in vivo imaging of tau protein. Therefore, we conducted a systematic review and meta-analysis of tau protein burden in PD cognitive impairment (PDCI), PD dementia (PDD), and other neurodegenerative diseases and explored the potential of the tau PET tracer as a biomarker for the diagnosis of PDCI. Methods PubMed, Embase, the Cochrane Library, and Web of Science databases were systematically searched for studies published till 1 June 2022 that used PET imaging to detect tau burden in the brains of PD patients. Standardized mean differences (SMDs) of tau tracer uptake were calculated using random effects models. Subgroup analysis based on the type of tau tracers, meta-regression, and sensitivity analysis was conducted. Results A total of 15 eligible studies were included in the meta-analysis. PDCI patients (n = 109) had a significantly higher tau tracer uptake in the inferior temporal lobe than healthy controls (HCs) (n = 237) and had a higher tau tracer uptake in the entorhinal region than PD with normal cognition (PDNC) patients (n = 61). Compared with progressive supranuclear palsy (PSP) patients (n = 215), PD patients (n = 178) had decreased tau tracer uptake in the midbrain, subthalamic nucleus, globus pallidus, cerebellar deep white matter, thalamus, striatum, substantia nigra, dentate nucleus, red nucleus, putamen, and frontal lobe. Tau tracer uptake values of PD patients (n = 178) were lower than those of patients with Alzheimer's disease (AD) (n = 122) in the frontal lobe and occipital lobe and lower than those in patients with dementia with Lewy bodies (DLB) (n = 55) in the occipital lobe and infratemporal lobe. Conclusion In vivo imaging studies with PET could reveal region-specific binding patterns of the tau tracer in PD patients and help in the differential diagnosis of PD from other neurodegenerative diseases. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/.

Objectives To evaluate the difference of tau burden between patients with progressive supranuclear palsy (PSP) and healthy controls (HCs) or other neurodegenerative diseases using tau-positron emission tomography (PET) imaging.MethodsA systematic search on PubMed, Embase, and Web of Science databases was performed for tau-PET studies in PSP patients, up to April 1, 2022. Standardized mean differences (SMDs) of tau tracer uptake were calculated using random-effects models. Subgroup analysis based on the type of tau tracers, meta-regression, and sensitivity analysis were conducted.ResultsTwenty-seven studies comprising 553 PSP, 626 HCs, and 406 other neurodegenerative diseases were included. Compared with HCs, PSP patients showed elevated tau binding in basal ganglia, midbrain, dentate nucleus, cerebellar white matter, and frontal lobe with decreasing SMD (SMD: 0.390–1.698). Compared with Parkinson’s disease patients, increased tau binding was identified in the midbrain, basal ganglia, dentate nucleus, and frontal and parietal lobe in PSP patients with decreasing SMD (SMD: 0.503–1.853). PSP patients showed higher tau binding in the subthalamic nucleus (SMD = 1.351) and globus pallidus (SMD = 1.000), and lower binding in the cortex and parahippocampal gyrus than Alzheimer’s disease patients (SMD: − 2.976 to − 1.018). PSP patients showed higher midbrain tau binding than multiple system atrophy patients (SMD = 1.269).Conclusion Tau PET imaging indicates different topography of tau deposition between PSP patients and HCs or other neurodegenerative disorders. The affinity and selectivity of tracers for 4R-tau and the off-target binding of tracers should be considered when interpreting the results.