Disrupted topologic efficiency of brain functional connectome in de novo Parkinson's disease with depression.

Growing evidence supports that depression in Parkinson's disease (PD) depends on disruptions in specific neural networks rather than regional dysfunction. According to the resting-state functional magnetic resonance imaging data, the study attempted to decipher the alterations in the topological properties of brain networks in de novo depression in PD (DPD). The study also explored the neural network basis for depressive symptoms in PD. We recruited 20 DPD, 37 non-depressed PD and 41 healthy controls (HC). The Graph theory and network-based statistical methods helped analyse the topological properties of brain functional networks and anomalous subnetworks across these groups. The relationship between altered properties and depression severity was also investigated. DPD revealed significantly reduced nodal efficiency in the left superior temporal gyrus. Additionally, DPD decreased five hubs, primarily located in the temporal-occipital cortex, and increased seven hubs, mainly distributed in the limbic cortico-basal ganglia circuit. The betweenness centrality of the left Medio Ventral Occipital Cortex was positively associated with depressive scores in DPD. In contrast to HC, DPD had a multi-connected subnetwork with significantly lower connectivity, primarily distributed in the visual, somatomotor, dorsal attention and default networks. Regional topological disruptions in the temporal-occipital region are critical in the DPD neurological mechanism. It might suggest a potential network biomarker among newly diagnosed DPD patients.

Altered functional connectivity of the primary motor cortex in tremor dominant and postural instability gait difficulty subtypes of early drug-naive Parkinson's disease patients.

Background: The primary motor cortex (M1) is an important hub in the motor circuitry of Parkinson's disease (PD), but the subregions' function and their correlation to tremor dominant (TD) and postural instability and gait disturbance (PIGD) with PD remain unclear. This study aimed to determine whether the functional connectivity (FC) of the M1 subregions varied between the PD and PIGD subtypes. Methods: We recruited 28 TD patients, 49 PIGD patients, and 42 healthy controls (HCs). M1 was divided into 12 regions of interest using the Human Brainnetome Atlas template to compare FC among these groups. Results: Compared with HCs, TD and PIGD patients exhibited increased FC between the left upper limb region (A4UL_L) and the right caudate nucleus (CAU)/left putamen (PUT), between the right A4UL (A4UL_R) and the left anterior cingulate and paracingulate gyri (ACG)/bilateral cerebellum4_5 (CRBL4_5)/left PUT/right CAU/left supramarginal gyrus/left middle frontal gyrus (MFG), as well as decreased connectivity between the A4UL_L and the left postcentral gyrus and the bilateral cuneus, and between the A4UL_R and the right inferior occipital gyrus. TD patients showed increased FC between the right caudal dorsolateral area 6 (A6CDL_R) and the left ACG/right MFG, between the A4UL_L and the right CRBL6/right middle frontal gyrus, orbital part/bilateral inferior frontal gyrus, and orbital part (ORBinf), and between the A4UL_R and the left ORBinf/right MFG/right insula (INS). PIGD patients displayed increased connectivity between the A4UL_L and the left CRBL4_5. Compared with PIGD patients, TD patients exhibited increased connectivity between the A6CDL_R and the left ACG/right MFG and between the A4UL_R and the left ACG/left ORBinf/right INS/right MFG. Furthermore, in TD and PIGD groups, the FC strength between the A6CDL_R and right MFG was negatively correlated with PIGD scores, while the FC strength between the A4UL_R and left ORBinf/right INS was positively correlated with TD scores and tremor scores. Conclusion: Our results demonstrated that early TD and PIGD patients share some common injury and compensatory mechanisms. TD patients occupied more resources in the MFG, ORBinf, INS, and ACG, which can be used as biomarkers to distinguish them from PIGD patients.

Functional and structural alterations as diagnostic imaging markers for depression in de novo Parkinson's disease.

Background: Depression in Parkinson's disease (PD) is identified and diagnosed with behavioral observations and neuropsychological measurements. Due to the large overlaps of depression and PD symptoms in clinical manifestations, it is challenging for neurologists to distinguish and diagnose depression in PD (DPD) in the early clinical stage of PD. The advancement in magnetic resonance imaging (MRI) technology provides potential clinical utility in the diagnosis of DPD. This study aimed to explore the alterations of functional and structural MRI in DPD to produce neuroimaging markers in discriminating DPD from non-depressed PD (NDPD) and healthy controls (HC). Methods: We recruited 20 DPD, 37 NDPD, and 41 HC matched in age, gender, and education years. The patients' diagnosis with PD was de novo. The differences in regional homogeneity (ReHo), voxel-wise degree centrality (DC), cortical thickness, cortical gray matter (GM) volumes, and subcortical GM volumes among these groups were detected, and the relationship between altered indicators and depression was analyzed. Moreover, the receiver operating characteristic (ROC) analysis was performed to assess the diagnostic efficacy of altered indicators for DPD. Results: Compared to NDPD and HC, DPD showed significantly increased ReHo in left dorsolateral superior frontal gyrus (DSFG) and DC in left inferior temporal gyrus (ITG), and decreased GM volumes in left temporal lobe and right Amygdala. Among these altered indicators, ReHo value in left DSFG and DC values in left ITG and left DSFG were significantly correlated with the severity of depression in PD patients. Comparing DPD and NDPD, the ROC analysis revealed a better area under the curve value for the combination of ReHo value in left DSFG and DC value in left ITG, followed by each independent indicator. However, the difference is not statistically significant. Conclusion: This study demonstrates that both functional and structural impairments are present in DPD. Among them, ReHo value of left DSFG and DC value of left ITG are equally well suited for the diagnosis and differential diagnosis of DPD, with a combination of them being slightly preferable. The multimodal MRI technique represents a promising approach for the classification of subjects with PD.

Monitoring Substantia Nigra Degeneration Using Free Water Imaging across Prodromal and Clinical Parkinson's Disease.

BACKGROUND: Substantia nigra (SN) free water has been suggested as a good surrogate marker in Parkinson's disease (PD). However, its usefulness for diagnosing prodromal PD (pPD) and monitoring disease progression warrants further validation. OBJECTIVE: The aim was to investigate SN free water values across prodromal and clinical stages of PD. METHODS: Four groups were enrolled in this study: 48 healthy controls (HC), 43 pPD patients, 50 de novo PD (dnPD) patients, and 49 medicated PD (mPD) patients. Based on diffusion tensor images, free water maps were calculated, and SN free water values were extracted from the anterior SN (ASN) and posterior SN (PSN). The SN free water values were compared among the four groups, and associations between free water and clinical symptoms were explored. The distinguishing power of PSN free water was evaluated using the receiver operating characteristic curve analysis. Follow-up was performed for 14 pPD patients. RESULTS: PSN free water in the pPD group was significantly higher than that in the HC group and significantly lower than that in the dnPD group. Surprisingly, the mPD group showed decreased PSN free water compared to the dnPD group. There was a positive correlation between motor symptoms and PSN free water in the pPD and dnPD groups. Longitudinal analysis showed a significant increase in PSN free water in pPD patients over time. CONCLUSIONS: The PSN free water increased from prodromal to early clinical stages, but the trend might be reversed in late disease stages. This biphasic trend should be considered when applying this marker in future studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Association of GBA genotype with motor and cognitive decline in Chinese Parkinson's disease patients.

Objective: Variants in the glucocerebrosidase (GBA) gene are the most common and significant risk factor for Parkinson's disease (PD). However, the impact of GBA variants on PD disease progression in the Chinese population remains unclear. This study aimed to explore the significance of GBA status on motor and cognitive impairment in a longitudinal cohort of Chinese patients with PD. Methods: The entire GBA gene was screened by long-range polymerase chain reaction (LR-PCR) and next generation sequencing (NGS). A total of 43 GBA-related PD (GBA-PD) and 246 non-GBA-mutated PD (NM-PD) patients with complete clinical data at baseline and at least one follow-up were recruited for this study. The associations of GBA genotype with rate of motor and cognitive decline, as measured by Unified PD Rating Scale (UPDRS) motor and Montreal Cognitive Assessment (MoCA), were assessed by linear mixed-effect models. Results: The estimated (standard error, SE) UPDRS motor [2.25 (0.38) points/year] and MoCA [-0.53 (0.11) points/year] progression rates in the GBA-PD group were significantly faster than those in the NM-PD group [1.35 (0.19); -0.29 (0.04) points/year; respectively]. In addition, the GBA-PD group showed significantly faster estimated (SE) bradykinesia [1.04 (0.18) points/year], axial impairment [0.38 (0.07) points/year], and visuospatial/executive [-0.15 (0.03) points/year] progression rates than the NM-PD group [0.62 (0.10); 0.17 (0.04); -0.07 (0.01) points/year; respectively]. Conclusion: GBA-PD is associated with faster motor and cognitive decline, specifically greater disability in terms of bradykinesia, axial impairment, and visuospatial/executive function. Better understanding of GBA-PD progression may help predict prognosis and improve clinical trial design.

Aberrant inter-network functional connectivity in drug-naive Parkinson's disease patients with tremor dominant and postural instability and gait difficulty.

Background: Insight into neural mechanisms of tremor dominant (TD) and postural instability and gait disorder (PIGD) subtypes in Parkinson's disease (PD) is vital for understanding pathophysiological hypotheses underlying this phenotype. However, network disturbances and their correlation with motor subtypes of PD remain unclear. We aimed to investigate the alterations of intra- and inter-network functional connectivity (FC) in drug-naive PD patients with different motor subtypes. Methods: Resting-state functional magnetic resonance imaging was performed on 25 drug-naive PD patients with TD (PD-TD) and 40 drug-naive PD patients with PIGD (PD-PIGD), and 37 healthy controls (HCs) underwent. The following networks were extracted using independent component analysis: sensorimotor network (SMN), left executive control network (LECN), right executive control network, anterior salience network (aSN), posterior salience network (pSN), ventral attention network (VAN), dorsal attention network (DAN), default mode network (DMN), visual network, and auditory network (AN). We measured FC values within and between these networks. Results: There were no detectable variations in intra-network FC. PD-PIGD group demonstrated lower FC between aSN and pSN, as well as between VAN and DMN, in contrast to PD-TD group. Particularly, the FC strength between VAN and DMN was positively correlated with TD and tremor scores, and the best fitting classification models of TD and PIGD subtypes were based on the FC between aSN and pSN. Compared with HCs, both PD-TD and PD-PIGD patients displayed decreased FC between two SMN subnetworks, while PD-TD patients exhibited increased FC between the SMN subnetwork and pSN, and between LECN and VAN. Furthermore, PD-PIGD patients demonstrated decreased FC between the SMN subnetwork and AN. Conclusions: The altered FC between aSN and pSN can be an imaging marker to distinguish PD-TD from PD-PIGD. We for the first time disclosed that the PD-TD patients compensated by increasing attention resources and the PD-PIGD patients displayed reduced FC between SMN and AN. Our findings provide a basis for identification and precision treatment of PD motor subtypes.

Integrated Clinical Features with Plasma and Multi-modal Neuroimaging Biomarkers to Diagnose Mild Cognitive Impairment in Early Drug-Naive Parkinson's Disease.

The pathogenesis of cognitive impairment in Parkinson's disease (PD) patients remains unclear, and there is no ideal diagnostic tool available at present. We assessed integrated clinical features with plasma and multi-modal neuroimaging biomarkers to identify mild cognitive impairment (MCI) in early drug-naive PD patients. 49 early drug-naive PD patients, including 26 with MCI (PD-MCI) and 23 with normal cognition (PD-NC), and 20 controls were recruited. Plasma markers [α-synuclein, beta-amyloid 1-40 (Aß40), beta-amyloid 1-42 (Aß42), and phosphorylated Tau 181 (p-Tau181) levels], functional connectivity (FC) of the default mode network, and cortical thickness (CTh) were evaluated to identify PD-MCI. The PD-MCI group had significantly higher plasma p-Tau181 levels and p-Tau181/Aß42 ratio and lower Aß42/Aß40 ratio compared to the PD-NC group. Compared to PD-NC, the PD-MCI group showed increased FC between left posterior cingulate cortex (pCC) and the left parahippocampal gyrus (PHG), and between the right hippocampal formation and the left anterior cingulate and paracingulate gyri, and the right middle temporal gyrus. Additionally, the PD-MCI group had thinner cortex thickness in the right lateral occipital and frontal pole compared to the PD-NC group. The final model combining clinical characteristics and several variables (age, sex, plasma p-Tau181 level, Aß42/Aß40 ratio, the right lateral occipital CTh, and the FC value between the left pCC and left PHG) had the highest diagnostic accuracy for PD-MCI (AUC = 0.987, 95% CI 0.903-1.000; p = 0.001 compared to age and sex alone). The combination of clinical features, plasma biomarkers, and multi-modal neuroimaging biomarkers can identify early cognitive decline in PD patients.

The impact of the COVID-19 pandemic-related quarantine on female sexual behavior: a cross-sectional study in China.

To investigate the impact and factors of home quarantine life on women's sexual lives and behaviors in different areas of China and analyze the prevalence of female sexual dysfunction (FSD) during the COVID-19 pandemic. We surveyed adult women who had a regular sexual life (including regular masturbation) and had been isolated at home for at least one month during the COVID-19 outbreak using online questionnaires. This survey recovered 678 complete questionnaires after screening. According to the findings, the overall score of the Female Sexual Function Inventory (FSFI) during the pandemic was 21.98 ± 6.38, the frequency of FSD was 61.9%, and the frequencies of FSD in Shanghai, Nanjing, and Ningxia were 60.6%, 75.2%, and 52.2%, respectively. The frequency of FSFI scores and other specific items (Desire, Arousal, Lubrication, Orgasm, Satisfaction, and Pain) varied significantly across the three regions (P < 0.05). The overall frequency of FSD in the masturbation population was 34.4%, which was lower than the frequency of FSD in women having paired sexual intercourse (60.1%) (p < 0.05). Further analysis revealed that the occurrence of FSD during the pandemic was related to different age stages, menopause, mode of delivery, level of anxiety and depression, and sexual lifestyles. The COVID-19 pandemic has had a great impact on people's spiritual and sexual lives, which are caused by multiple different variables related to both the individual and the environment. We should emphasize the importance of sexual health in epidemics, and having a harmonious and stable sex life will help us survive the boring life of isolation.

Zishen pingchan granules combined with pramipexole in the improvement of depressive symptoms in Parkinson's disease: a prospective, multicenter, randomized, double-blind, controlled clinical study.

BACKGROUND AND OBJECTIVE: Zishen Pingchan granule (ZPG), a traditional Chinese herbal recipe for treating Parkinson's disease (PD), is usually used as an add-on drug with some antiparkinsonian drugs in China. The objectives of this study were to evaluate the efficacy, safety, and tolerability of ZPG combined with pramipexole in the treatment of depression in PD (dPD). METHODS: A 12-week, multicenter, randomized, double-blind, and placebo-controlled study on ZPG was performed on a total of 200 patients who were treated with pramipexole but still had mild to moderate depressive symptoms. Patients were randomly divided into ZPG (n = 100) or placebo (n = 100). The primary effective result was the mean change from the baseline on the Hamilton Depression Scale 17 items (HAM-D-17) over 12 weeks and the clinical efficacy rate. Secondary endpoints were the mean change from the baseline in the Geriatric Depression Scale (GDS-15), Unified Parkinson's disease rating scale Part III (UPDRS III), Parkinson's quality of life scale (PDQ-8), and Parkinson's disease sleep scale (PDSS-2) over 12 weeks. RESULTS: After 12 weeks of treatment, ZPG significantly reduced the mean [95% confidence interval] HAMD score vs. placebo (- 1.43 scores [- 2.50, - 0.36]; p = 0.009). The clinical remission rate and responders of the ZPG group were higher than those of the placebo (46.1% vs. 31.0%; p = 0.041; 34.8% vs. 18.4%; p = 0.014). A significant improvement in the PDSS-2 score was also observed in the ZPG group compared with that in the placebo group (- 3.56 scores [- 5.77, - 1.35]; p = 0.002). A total of 7 patients (7.1%) in the ZPG group had mild adverse events (AEs) vs 9 patients (9%) in the placebo group. No severe AEs were observed in either group. The randomization and controlled clinical study revealed that ZPG was effective, safe, and well-tolerated. CONCLUSION: ZPG combined with pramipexole further reduced the depressive symptoms and improved the sleeping quality of PD patients. Trial registration The protocol was retrospectively registered at the Chinese Clinical Trial Registry, Unique identifier: ChiCTR1800019942, date of registration: December 9, 2018; http://www.chictr.org.cn/showproj.aspx?proj=30432.

Subjective Cognitive Complaints in Newly-Diagnosed Parkinson's Disease With and Without Mild Cognitive Impairment.

Background: Subjective cognitive complaints (SCCs) and mild cognitive impairment (MCI) are common among patients with Parkinson's disease (PD). However, the relationship between SCCs and MCI is not well understood. Herein, we aimed to investigate whether there are any differences in the prevalence and risk factors of SCCs between early PD patients with and without MCI. Methods: Overall, 108 newly diagnosed, untreated PD patients underwent comprehensive neuropsychological assessments. PD patients with mild cognitive impairment (PD-MCI) were diagnosed according to the MCI level II criteria. Furthermore, SCCs were measured with the Cognitive Complaints Interview (CCI). Logistic regression analysis, after adjusting for confounding variable, was performed in order to investigate risk factors of SCCs in PD-MCI patients and PD patients with normal cognition (PD-NC). Results: Furthermore, 42 (42.3%) participants reported SCCs and 53 (53.5%) participants were diagnosed with PD-MCI. The prevalence of SCCs in PD-MCI and PD-NC participants was 30.3% and 12.1%, respectively. Logistic regression analyses revealed that the presence of SCCs in PD-MCI group was significantly associated with Non-Motor Symptoms Questionnaire (NMSQ) score (OR = 1.340, 95%CI = 1.115-1.610, p = 0.002), while the presence of SCCs in PD-NC group was significantly associated with time of Stroop Color-Word Test card C (OR = 1.050, 95%CI = 1.009-1.119, p = 0.016). Conclusion: SCCs are frequent among patients with early PD. The prevalence and risk factor of SCCs are distinct in PD with and without MCI. These findings suggest that SCCs in early PD with different cognitive status appear to have different pathogenicity.