Male Parkinson's Disease Research Articles

Prevalence and associations of self-reported sleep problems in a large sample of patients with Parkinson's disease.

Sleep problems are important comorbid features of, and risk factors for, neurodegenerative diseases such as Parkinson's disease (PD). To assess the prevalence and associations of sleep problems in patients with PD we analysed data from almost 54,000 participants in the Fox Insight study, including data from 38,588 patients with PD. Sleep problems are common in PD, with ~84% of respondents with PD reporting difficulty falling or staying asleep. Experiences of insomnia, restless leg syndrome, vivid dreams, acting out dreams, and the use of sleep medication are over-represented in patients with PD compared with matched healthy controls. Male sex and PD onset before the age of 50 were also associated with a greater risk of sleep problems. A physician diagnosis of insomnia was associated with more symptoms of depression, impairment of cognition-dependent independence, and a lower quality of life. Sleep problems were also associated with a higher prevalence of OFF periods compared with PD patients without sleep problems. 6.7% of PD patients endorsed sleep complaints as their most bothersome symptom, and reported non-specific poor sleep quality as the most common sleep problem. These patients also had a better quality of life and lower depression and cognitive impairments than patients for whom postural instability was their most bothersome symptom, indicating the relative burden of sleep problems is contextualised by the severity of motor symptoms. Overall, these findings reinforce the high prevalence of sleep problems in a very large sample of PD patients, and indicate important associations of sleep problems with daily function and quality of life in PD.

Evaluating prognostic factors for falls in Parkinson's disease: A sex-based analysis.

Falls are a common and debilitating complication in Parkinson's disease (PD). Previous studies have primarily focused on cohorts with prevalent falls or advanced disease stages. This study assessed risk factors for falls in early-stage falls-naïve cohort stratified by sex. A total of 172 PD patients (<5 years disease duration) were selected from a registry-based study that reported no falls at baseline. All patients were assessed with a standardized data extraction form and falls were defined according to UPDRS Item 13. Hazard Ratios were calculated with univariable and stepwise multivariable Cox Proportional Hazard regression models. Among the study sample, 61 (35.4 %) patients were female. At baseline, female and male PD groups were comparable in terms of age, disease duration, and UPDRS scores, although female PD patients had higher scores for UPDRS IV. Over a mean follow-up period of 3.9 (3.0) years, falls were reported in 13 female (21.3 %) and 18 male (16.2 %) PD patients. In female PD, motor fluctuations (HR [95 %] = 1.8 [1.3 - 2.6], p < 0.001) and postural stability (HR [95 %] = 4.2 [1.6 - 10.6], p = 0.003) emerged as significant predictors for falls, whereas in male PD, stepwise Cox regression selected freezing of gait (HR [95 %] = 2.0 [1.0 - 4.2], p = 0.053) and postural instability (HR [95 %] = 2.2 [0.89 - 5.4], p = 0.089) as the primary predictors for falls, although they were non-significant. Our findings suggest that the risk factors for falls differ between female and male early-stage PD patients, which may have important implications for clinical management.

Correlation Analysis between Cortical Structural Features and Acoustic Features in Patients with Parkinson's Disease

Parkinson disease (PD) is a progressive neurodegenerative disease. The aim of this study is to investigate the association between acoustic and cortical brain features in Parkinson's disease patients. We recruited 19 (eight females, 11 males) Parkinson's disease patients and 19 (eight females, 11 males) healthy subjects to participate in the experiment. Speech samples of three vowels (/i/, /a/, /u/), six plosives (/p/, /pʰ/, /t/, /tʰ/, /k/, /kʰ/), and three voiced consonants (/l/, /m/, /n/) were collected for the experiment, and the acoustic parameters were extracted for fundamental frequency (F0), voice onset time (VOT), voicing onset-vocalic voicing onset (VO-VVO), first formant (F1), second formant (F2), third formant (F3), first bandwidth (B1), second bandwidth (B2), third bandwidth (B3), Jitter, Shimmer, andHarmonics-to-noise ratio (HNR). We also used Ingenia CX 3.0T to complete the cranial magnetic resonance scanning and did image processing based on the Desikan-Killiany-Tourville Atlas. We assessed the differences in acoustic and neuroimaging parameters between the PD andhealthy controls (HCs) groups using the Levene's test (LT), two-sample independent t test (TT), and Mann-Whitney U test (MWUT), and calculated Spearman's bias correlations for acoustic and neuroimaging parameters in the PD and HC groups, respectively. The results showed that in acoustic features, based on the results of the TT, it can be seen that the F3 of the PD group regarding the vowel /i/ is significantly smaller than that of the HC group. The jitter on the vowel /u/ was significantly higher in the male PD group than in the male HC group. For other acoustic measures, there were no statistically significant differences between the two groups. In the cortical features, the thickness, area, and volume of the cortex were reduced in the vast majority of the brains of the PD patients, however, there is also a small portion of the cortex that appears to be thickened. In the correlation analysis between cortical and acoustic features, F0, F1, F2, F3, B2, B3, VO-VVO, Jitter, HNR, and VOT acoustic parameters showed significant and strong correlation with thickness, area, and volume of cortical sites such as frontal, temporal, entorhinal, fusiform, andprecuneus in PD patients, whereas no significant correlation was found in HC group. This suggests that Parkinson's disease does have an effect on the acoustic and cortical features of the patient's brain, and that there is a correlation between the two features.

Importance of health history analysis in Parkinson's disease

The objective of this research article is to investigate the impact of various health history factors on the risk of developing Parkinson's disease (PD). From the medical history we can identify PD Symptoms and this also help to detect the progression of PD symptoms. By conducting statistical analyses, the study seeks to identify independent risk and protective factors for Parkinson's disease (PD), considering variations in impact across genders and BMI categories. IntroductionIn the diagnosis of PD the analysis of previous health history is very rare in practice while the main diagnosis have been done through the different motor and non-motor symptoms taking in consideration besides the cardinal symptoms of PD for identification and determination the stages of PD. Here we have analyzed the impact of 56 different diseases, symptoms, and surgeries which a subject may have experienced in their life before PD, considered as a health history. MethodsThe behavioral impact for each types of health history have been analyzed statistically with 31,265 subjects including PD, and Control. In this analysis we have calculated the variation of impact for both the Male, and Female, as well as subjects BMI. Results98.12 % PD patients, where 97.63 % Male PD, and 98.71 % Female PD were found with at least one health history record. Coronary heart disease odds ratio (OR) 2.15 (1.85–2.51), Colon Cancer OR 2.11 (1.45–3.05), Cranial brain surgery OR 6.21 (5.11–7.56) have the higher risks to PD. Having the history of Asthma OR 0.66 (0.6–0.72), Anemia OR 0.56 (0.51–0.63), Cirrhosis in Liver OR 0.7 (0.57–0.86), Cosmetic surgery OR 0.7 (0.64–0.77), and Gastritis OR 0.78 (0.71–0.87) have been found to be protective to PD. The risk of developing PD varies between male, and female including subjects BMI for each individual health history types. The diseases which reduce the oxygen saturation in blood like, anemia, asthma, and thalassemia act as protective to PD. ConclusionsIn this study we have analyzed fifty six diseases which include surgeries as a health history of PD patients. Study suggests that a thorough health history could greatly aid in understanding the onset and progression of Parkinson's disease (PD).

Sex-dependent associations of serum BDNF, glycolipid metabolism and cognitive impairments in Parkinson's disease with depression: a comprehensive analysis.

Brain-derived neurotrophic factor (BDNF) and glycolipid metabolism have been implicated in cognitive impairments and depression among Parkinson's disease (PD). However, the role of sex differences in this relationship remains elusive. This study aimed to investigate the potential sex differences in the link between serum BDNF levels, glycolipid metabolism and cognitive performance among depressive PD patients. PD patients comprising 108 individuals with depression and 108 without depression were recruited for this study. Cognitive function was assessed using the Montreal Cognitive Assessment Beijing version (MOCA-BJ). The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HAMD-17), while motor symptoms were evaluated using the Revised Hoehn and Yahr rating scale (H-Y) and the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III). Laboratory testing and enzyme-linked immunosorbent assay (ELISA) are used to measure serum levels of glycolipid metabolism and BDNF. Females showed superior performance in delayed recall (all p < 0.05), male PD patients exhibited higher scores in naming tasks compared to females in non-depression group. There was no sex differences in serum BDNF levels between depression and non-depression groups. Liner regression analysis indicated BDNF as an independent risk factor for language deficits in male PD patients with depression (p < 0.05), while cholesterol (CHOL) emerged as a cognitive influencing factor, particularly in delayed recall among male PD patients with depression (p < 0.05). Our study reveals extensive cognitive impairments in PD patients with depression. Moreover, BDNF and CHOL may contribute to the pathological mechanisms underlying cognitive deficits, particularly in male patients with depression.

Unraveling sex differences in Parkinson's disease through explainable machine learning

Sex differences affect Parkinson's disease (PD) development and manifestation. Yet, current PD identification and treatments underuse these distinctions. Sex-focused PD literature often prioritizes prevalence rates over feature importance analysis. However, underlying aspects could make a feature significant for predicting PD, despite its score. Interactions between features require consideration, as do distinctions between scoring disparities and actual feature importance. For instance, a higher score in males for a certain feature doesn't necessarily mean it's less important for characterizing PD in females. This article proposes an explainable Machine Learning (ML) model to elucidate these underlying factors, emphasizing the importance of features. This insight could be critical for personalized medicine, suggesting the need to tailor data collection and analysis for males and females. The model identifies sex-specific differences in PD, aiding in predicting outcomes as “Healthy” or “Pathological”. It adopts a system-level approach, integrating heterogeneous data - clinical, imaging, genetics, and demographics - to study new biomarkers for diagnosis. The explainable ML approach aids non-ML experts in understanding model decisions, fostering trust and facilitating interpretation of complex ML outcomes, thus enhancing usability and translational research. The ML model identifies muscle rigidity, autonomic and cognitive assessments, and family history as key contributors to PD diagnosis, with sex differences noted. The genetic variant SNCA-rs356181 may be more significant in characterizing PD in males. Interaction analysis reveals a greater occurrence of feature interplay among males compared to females. These disparities offer insights into PD pathophysiology and could guide the development of sex-specific diagnostic and therapeutic approaches.

Antagonism of metabotropic glutamate receptor type 5 prevents levodopa-induced dyskinesia development in a male rat model of Parkinson's disease: Electrophysiological evidence.

Levodopa-induced dyskinesia (LID) is a common complication in patients with advanced Parkinson's disease (PD) undergoing treatment with levodopa. Glutamate receptor antagonists can suppress LID; however, the underlying mechanisms remain unclear. Here, we aimed to evaluate the effect of 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP), a metabotropic glutamate receptor 5 (mGluR5) antagonist, on dyskinesia. We recorded the neuronal activity of the entopeduncular nucleus and examined responses to cortical electric stimulation in the control group (n = 6) and three groups of rats (male PD model). Saline was intraperitoneally administered to dopamine lesioned (DL) rats (n = 6), levodopa/benserazide (L/B) was administered to LID rats (n = 8), and L/B combined with MTEP was administered to MTEP rats (n = 6) twice daily for 14 days. We administered L/B to LID and MTEP rats 48 h after the final administration of MTEP to examine the chronic effect of MTEP. The control and DL groups did not have LID. The MTEP group had less LID than the LID group (p < .01) on day 1 and day 18. The control group had a typical triphasic pattern consisting of early excitation (early-Ex), inhibition, and late excitation (late-Ex). However, the inhibition phase disappeared, was partially observed, and was fully suppressed in the DL, LID, and MTEP groups, respectively. The cortico-striato-entopeduncular pathway is important in the pathophysiology of LID. mGluR5 antagonism suppresses LID progression by preventing physiological changes in the cortico-striato-entopeduncular pathway. Future studies are required to validate these results.

Quantification of Circulating Cell-Free DNA in Idiopathic Parkinson's Disease Patients.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders globally and leads to an excessive loss of dopaminergic neurons in the substantia nigra of the brain. Circulating cell-free DNA (ccf-DNA) are double-stranded DNA fragments of different sizes and origins that are released into the serum and cerebrospinal fluid (CSF) due to cell death (i.e., necrosis and apoptosis) or are actively released by viable cells via exocytosis and NETosis. Using droplet digital polymerase chain reaction (ddPCR), we comprehensively analyzed and distinguished circulating cell-free mitochondrial DNA (ccf mtDNA) and circulating cell-free nuclear DNA (ccfDNA) in the serum and CSF of PD and control patients. The quantitative analysis of serum ccf-DNA in PD patients demonstrated a significant increase in ccf mtDNA and ccfDNA compared to that in healthy control patients and a significantly higher copy of ccf mtDNA when compared to ccfDNA. Next, the serum ccf mtDNA levels significantly increased in male PD patients compared to those in healthy male controls. Furthermore, CSF ccf mtDNA in PD patients increased significantly compared to ccfDNA, and ccf mtDNA decreased in PD patients more than it did in healthy controls. These decreases were not statistically significant but were in agreement with previous data. Interestingly, ccf mtDNA increased in healthy control patients in both serum and CSF as compared to ccfDNA. The small sample size of serum and CSF were the main limitations of this study. To the best of our knowledge, this is the first comprehensive study on serum and CSF of PD patients using ddPCR to indicate the distribution of the copy number of ccf mtDNA as well as ccfDNA. If validated, we suggest that ccf mtDNA has greater potential than ccfDNA to lead the development of novel treatments for PD patients.

Inflammation and heterogeneity in synucleinopathies.

Neurodegenerative diseases represent a huge healthcare challenge which is predicted to increase with an aging population. Synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), present complex challenges in understanding their onset and progression. They are characterized by the abnormal aggregation of α-synuclein in the brain leading to neurodegeneration. Accumulating evidence supports the existence of distinct subtypes based on the site of α-synuclein aggregation initiation, genetics, and, more recently, neuroinflammation. Mediated by both central nervous system-resident cells, peripheral immune cells, and gut dysbiosis, neuroinflammation appears as a key process in the onset and progression of neuronal loss. Sex-based differences add another layer of complexity to synucleinopathies, influencing disease prevalence - with a known higher incidence of PD in males compared to females - as well as phenotype and immune responses. Biological sex affects neuroinflammatory pathways and the immune response, suggesting the need for sex-specific therapeutic strategies and biomarker identification. Here, we review the heterogeneity of synucleinopathies, describing the etiology, the mechanisms by which the inflammatory processes contribute to the pathology, and the consideration of sex-based differences to highlight the need for personalized therapeutics.

The intestinal microbiota exerts a sex-specific influence on neuroinflammation in a Parkinson's disease mouse model

Parkinson's disease (PD) is a neurodegenerative disorder characterised by chronic and progressive symptoms; it is more prevalent in men than in women. The sex-specific influence of the intestinal microbiota has been associated with some neurodegenerative diseases, but the relationship with PD is currently unclear. In this study, we treated mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to establish a PD mouse model, and we utilised an antibiotic cocktail (Abx) to deplete the intestinal microbiota to evaluate the influence of the intestinal microbiota on male and female PD mice. MPTP treatment obviously caused bradykinesia and low mobility in female and male mice. Meanwhile, Abx treatment exerted a greater effect on male mice than female mice. Western blotting and immunofluorescence revealed that male mice treated with MPTP had higher expression of α-synuclein and proteins related to neuroinflammation and intestinal inflammation based on activation of glial cells and the TLR4–MyD88 signalling pathway. The sex-specific differences could be due to the different composition of the intestinal microbiota. Specifically, female mice had significantly higher abundance of Allobaculum, Turicibacter and Ruminococcus than male mice. Moreover, the abundance of the probiotic genus Bifidobacterium showed opposite trends in male and female mice. Our results indicate that the intestinal microbiota has an important effect on PD mice, especially male mice, by influencing neuroinflammation through the microbiota–gut–brain axis. In the future, there should be a focus on providing more reliable evidence for the pathogenesis and precise treatment of PD.

The value of ultrasound measurement of muscle thickness at different sites and shear wave elastography in Parkinson's disease with sarcopenia: a pilot study.

Patients with Parkinson's disease (PD) and sarcopenia often exhibit resilience, frailty, disability, and depression, highlighting the complex and interrelated nature of these conditions. Despite the presence of clinical manifestations of muscle atrophy in both PD and sarcopenia, accurately discerning the coexistence of sarcopenia in PD patients remains a challenging task with significant implications for treatment strategies and prognostic assessments. This study aims to elucidate the specific ultrasonic diagnostic parameters associated with PD accompanied by sarcopenia through a comparative analysis of muscle ultrasound parameters in patients with PD, thereby presenting a novel approach for rapid identification of this condition. A total of 110 participants were enrolled in this study, including patients with PD and control subjects. Demographic data, clinical characteristics, physical performance tests, appendicular skeletal muscle mass index (ASMI), bioelectrical impedance analysis and muscle ultrasound measurements were collected from all participants. The muscle ultrasound measurements encompassed assessments of muscle thickness, pennation angle and shear wave elastography at various anatomical sites. Parkinson's disease patients exhibited decreased muscle strength and physical performance, and increased shear wave elastography value. In PD patients with sarcopenia, body circumference, including calf circumference, mid-arm circumference, Waist-to-Hip Ratio and body mass index (BMI) were all significantly decreased. Biceps brachii muscle thickness (MT) and gastrocnemius MT decreased in PD patients with sarcopenia and low ASMI. Binary logistic regression analysis revealed that male PD patients, BMI and gastrocnemius MT were predictive factors for ASMI in PD patients. Biceps brachii MT and gastrocnemius MT are important indicators for distinguishing whether PD patients have sarcopenia. Male patients, low BMI and gastrocnemius MT were identified as valid predictors of low ASMI in PD patients. The findings of this study provide important insights into the use of muscle ultrasound in the diagnosis of PD with sarcopenia.

Evaluation of the role of FMR1 CGG repeat allele in Parkinson's disease from the Chinese population.

There is controversial evidence that FMR1 premutation or "gray zone" (GZ) allele (small CGG expansion, 45-54 repeats) was associated with Parkinson's disease (PD). We aimed to explore further the association between FMR1 CGG repeat expansions and PD in a large sample of Chinese origin. We included a cohort of 2,362 PD patients and 1,072 controls from the Parkinson's Disease and Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) in this study and conducted repeat-primed polymerase chain reaction (RP-PCR) for the size of FMR1 CGG repeat expansions. Two PD patients were detected with FMR1 premutation (61 and 56 repeats), and the other eleven PD patients were detected with the GZ allele of FMR1 CGG repeat expansions. Those thirteen PD patients responded well to levodopa and were diagnosed with clinically established PD. Specifically, one female PD patient with GZ allele was also found with premature ovarian failure. However, compared to healthy controls, we found no significant enrichment of GZ allele carriers in PD patients or other subgroups of PD cases, including the subgroups of female, male, early-onset, and late-onset PD patients. Furthermore, we did not find any correlation between the FMR1 gene CGG repeat sizes and age at onset of PD. It suggested that FMR1 premutation was related to PD, but the GZ allele of FMR1 CGG repeat expansions was not significantly enriched in PD cases of Chinese origin. Further larger multiple ethnic studies are needed to determine further the role of the FMR1 GZ allele in PD.

Sex Differences in Brain Structure in de novo Parkinson's Disease: A Cross-Sectional and Longitudinal Neuroimaging Study.

Parkinson's disease (PD) varies in occurrence, presentation, and severity between males and females. However, the sex effects on the patterns of brain structure, cross-sectionally and longitudinally, are still unclear. We aimed to compare sex differences in brain features cross-sectionally and longitudinally using grey matter volume (GMV) and cortical thickness in a large sample of newly diagnosed drug-naive PD patients. Cognitive assessments and structural MR images of 262 PD patients (171 males) and 113 healthy controls (68 males) were selected from the Parkinson's Progression Markers Initiative. Of these, 97 PD patients (66 males) completed 12- and 24-month follow-up examinations. After regressing out the expected effects of age and sex, brain maps of GMV and cortical thickness were compared using two-sample t tests cross-sectionally and were compared using repeated measurement analyses of variance longitudinally. At baseline, male PD patients exhibited a greater extent of brain atrophy and cortical thickness reduction than females, which mainly occurred in the cerebellum, frontal lobe, parietal lobe, and temporal lobe. At follow-up, female and male PD patients showed similar dynamics of disease progression, as both groups declined over time while the females maintained the advantage. The cortical thickness of the right precentral gyrus at baseline was negatively associated with the longitudinal changes of motor function in male PD patients. The current findings might demonstrate sex effect in neuroanatomy during the course of PD, provide new insights into the neurodegenerative process, and facilitate the development of more effective sex-specific therapeutic strategies.

Exploring the alteration of gut microbiota and brain function in gender-specific Parkinson's disease based on metagenomic sequencing.

The role of the microbiota-gut-brain axis in Parkinson's disease (PD) has received increasing attention. Although gender differences are known to an essential role in the epidemiology and clinical course of PD, there are no studies on the sex specificity of the microbiota-gut-brain axis in the development and progression of PD. Fresh fecal samples from 24 PD patients (13 males, 11 females) were collected for metagenomic sequencing. The composition and function of the gut microbiota were analyzed by resting-state functional magnetic resonance imaging (fMRI). Gender-dependent differences in brain ALFF values and their correlation with microbiota were further analyzed. The relative abundance of Propionivibrio, Thermosediminibacter, and Flavobacteriaceae_noname was increased in male PD patients. LEfse analysis showed that Verrucomicrobial, Akkermansiaceae, and Akkermansia were dominant in the males. In female patients, the relative abundance of Propionicicella was decreased and Escherichia, Escherichia_coli, and Lachnospiraceae were predominant. The expression of the sesquiterpenoid and triterpenoid biosynthesis pathways was increased in male PD patients and was statistically different from females. Compared to the Male PD patients, female patients showed decreased ALFF values in the left inferior parietal regions, and the relative abundance of Propionivibrio was positively correlated with the regional ALFF values. Our study provides novel clinical evidence of the gender-specific relationship between gut microbiota alterations and brain function in PD patients, highlighting the critical role of the microbiota-gut-brain axis in gender differences in PD.

Sex hormones differentially contribute to Parkinson disease in males: A multimodal biomarker study.

Parkinson disease (PD) presents relevant sex-related differences in epidemiology, pathophysiology, and clinical features, with males being more vulnerable to the disease. Sex hormones might have a role, as the experimental models suggest; however, human-based evidence is scarce. Here, we integrated multimodal biomarkers to investigate the relationships between circulating sex hormones and clinical-pathological features in male PD patients. A cohort of 63 male PD patients underwent comprehensive clinical evaluation of motor and nonmotor disturbances; measurement of estradiol, testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) blood levels; and cerebrospinal fluid (CSF) assay of total α-synuclein, amyloid-β-42, amyloid-β-40, total tau, and phosphorylated-181 tau levels. A subgroup of 47 PD patients underwent brain volumetry by 3-T magnetic resonance imaging for further correlations. A control group of 56 age-matched individuals was enrolled for comparative analyses. Male PD patients had higher estradiol and testosterone levels than controls. Estradiol had independent inverse associations with Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part 3 score and disease duration; it was also lower in nonfluctuating patients. Testosterone had inverse independent correlations with CSF α-synuclein and right globus pallidus volume. FSH and LH had age-dependent correlations with cognitive impairment and CSF amyloid-β-42/amyloid-β-40 ratio. The study suggested that sex hormones could differentially contribute to clinical-pathological features of PD in male patients. Whereas estradiol might have a protective role in motor impairment, testosterone might be involved in male vulnerability to PD neuropathology. Gonadotropins instead might mediate age-dependent phenomena of amyloidopathy and cognitive decline.

The High Value of External Anal- and Urethral-Sphincter Electromyography in Differential Diagnosis with MSA-P, PD, and PSP.

It is a challenge to differentiate multiple system atrophy parkinsonism (MSA-P), Parkinson's disease (PD), and progressive supranuclear palsy (PSP). We aimed to explore the value of external anal-sphincter electromyography (EAS-EMG) and urethral-sphincter electromyography (US-EMG) in differential diagnosis with MSA-P, PD, and PSP. A total of 149 subjects, including 27 MSA-P, 100 PD, and 22 PSP, were recruited. The average duration and amplitude of motor unit potentials (MUPs), percentage of polyphasic MUPs, amplitude during strong contraction, and recruitment pattern during maximal voluntary contraction were recorded. The differences in EAS-EMG and US-EMG results between MSA-P, PD, and PSP were analyzed. In EAS-EMG examination, the average duration of MUPs of MSA-P was significantly longer than that of PD and PSP; the percentage of polyphasic MUPs and the ratio of simple phase and simple-mix phase of MSA-P and PSP were significantly higher than that of PD; the amplitude during strong contraction of MSA-P was significantly lower than that of PD. In US-EMG examination, the average duration of MUPs in male MSA-P was significantly longer than that in male PD and PSP; the ratio of simple phase and simple-mix phase in male MSA-P was significantly higher than that in male PD; there was no statistical difference in US-EMG indexes between male PD and PSP male. And because only one female PSP was examined, only female MSA-P and PD were compared, the average duration of MUPs in female MSA-P was significantly longer than that in female PD; the ratio of simple phase and simple-mix phase in female MSA-P was significantly higher than that in female PD. The average duration of MUPs and the ratio of the simple phase and simple-mix phase of EAS-EMG and US-EMG all can provide the basis for the differential diagnosis between MSA-P and PD. US-EMG can be used as a supplement to differentiate MSA-P from PD when EAS-EMG is limited. The only discriminating indicator between MSA-P and PSP seems to be the average duration of MUPs of EAS-EMG and US-EMG. There is still a lack of diagnostic electromyography indicators between PD and PSP.

Sex differences in Parkinson disease-associated episodic memory and processing speed deficits.

This study aims to address a gap in the data on cognitive sex differences in persons living with Parkinson disease (PD). There is some evidence that cognitive dysfunction is more severe in male PD, however data on episodic memory and processing speed is incomplete. One hundred and sixty-seven individuals with a diagnosis of PD were included in this study. Fifty-six of those individuals identified as female. The California Verbal Learning Test 1st edition and the Wechsler Memory Scale 3rd edition were used to evaluate verbal and visuospatial episodic memory and the Wechsler Adult Intelligence Scale 3rd edition was used to evaluate processing speed. Multivariate analysis of covariance was used to identify sex-specific differences across groups. Our results show that males with PD performed significantly worse than females in verbal and visuospatial recall as well as a trend for the processing speed task of coding. Our finding of superior performance among females with PD in verbal episodic memory is consistent with reports in both healthy and PD individuals; however, females outperforming males in measures of visuospatial episodic memory is unique to PD. Cognitive deficits preferentially affecting males appear to be associated with frontal lobe-related function. Therefore, males may represent a disease subgroup more susceptible to disease mechanisms affecting frontal lobe deterioration and cognitive disturbances in PD.

Voltage-Gated Proton Channel Hv1 Regulates Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson's Disease Models.

Although the precise mechanisms for neurodegeneration in Parkinson's disease (PD) are unknown, evidence suggests that neuroinflammation is a critical factor in the pathogenic process. Here, we sought to determine whether the voltage-gated proton channel, Hv1 (HVCN1), which is expressed in microglia and regulates NADPH oxidase, is associated with dopaminergic neurodegeneration. We utilized data mining to evaluate the mRNA expression of HVCN1 in the brains of PD patients and controls and uncovered increased expression of the gene encoding Hv1, HVCN1, in the brains of PD patients compared to controls, specifically in male PD patients. In an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 4 × 16 mg/kg) mouse model of PD, Hvcn1 gene expression was increased 2-fold in the striatum. MPTP administration to wild-type (WT) mice resulted in a ~65% loss of tyrosine hydroxylase positive neurons (TH+) in the substantia nigra (SN), while a ~39% loss was observed in Hv1 knockout (KO) mice. Comparable neuroprotective effects of Hv1 deficiency were found in a repeated-dose LPS model. Neuroprotection was associated with decreased pro-inflammatory cytokine levels and pro-oxidant factors in both neurotoxicant animal models. These in vivo results were confirmed in primary microglial cultures, with LPS treatment increasing Hvcn1 mRNA levels and Hv1 KO microglia failing to exhibit the LPS-mediated inflammatory response. Conditioned media from Hv1 KO microglia treated with LPS resulted in an attenuated loss of cultured dopamine neuron cell viability compared to WT microglia. Taken together, these data suggest that Hv1 is upregulated and mediates microglial pro-inflammatory cytokine production in parkinsonian models and therefore represents a novel target for neuroprotection.

Burden of Parkinson Disease in China, 1990–2019: Findings from the 2019 Global Burden of Disease Study

Introduction: China has the most people with Parkinson disease (PD) in the world and is estimated to have over half of the worldwide PD population. The objective of this study was to analyze the corresponding burden of PD in China for the past decades. Method: Data on disease burden related to PD in China were retrieved from the Global Burden of Disease (GBD) 2019 study. The estimated annual percentage changes (EAPCs) were calculated to assess temporal trends, and the ratio of years lived with disability (YLDs) to disability-adjusted life years (DALYs) was used as an index to evaluate the healthcare system. Result: Nationally, the burden of PD increased from 1990 to 2019. Although the age-standardized incidence rate (ASIR) increased, the age-standardized death rate (ASDR) and age-standardized DALY rate both decreased. Age-standardized rates of PD in males remained higher than those in females, but trends in ASDR and the age-standardized DALY rate for females showed a pronounced decrease. The most remarkable increase in the ASIR was in individuals aged 45–49 years, with an EAPC of 1.74 (95% confidence interval, 1.26–2.21). The YLDs:DALYs ratio continuously increased compared with global figures and even with countries with high sociodemographic index (SDI). Conclusion: Although ASDR and age-standardized DALY rates for PD have been declining, the burden of PD still needs attention as the total numbers have increased over the period. Generally, the greater burden of PD was in males. A sound health system with services tailored to PD continues to be required in the future.

Respiratory deficits in a female rat model of Parkinson's disease.

What is the central question of this study? How does the 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease model affect the respiratory response in female rats? What effect does ovariectomy have on that response? What is the main finding and its importance? The results suggest a protective effect of ovarian hormones in maintaining normal neuroanatomical integrity of the medullary respiratory nucleus in females. It was observed that ovariectomy alone reduced neurokinin-1 density in the pre-Bötzinger complex and Bötzinger complex, and there was an incremental effect of 6-OHDA and ovariectomy on retrotrapezoid nucleus neurons. Emerging evidence indicates that the course of Parkinson's disease (PD) includes autonomic and respiratory deficiencies in addition to the classical motor symptoms. The prevalence of PD is lower in women, and it has been hypothesized that neuroprotection by ovarian hormones can explain this difference. While male PD animal models present changes in the central respiratory control areas, as well as ventilatory parameters under normoxia and hypercapnia, little is known about sex differences regarding respiratory deficits in this disease background. This study aimed to explore the neuroanatomical and functional respiratory changes in intact and ovariectomized (OVX) female rats subjected to chemically induced PD via a bilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA). The respiratory parameters were evaluated by whole-body plethysmography, and the neuroanatomy was monitored using immunohistochemistry. It was found that dopaminergic neurons in the substantia nigra and neurokinin-1 receptor density in the rostral ventrolateral respiratory group, Bötzinger and pre-Bötzinger complex were reduced in the chemically induced PD animals. Additionally, reduced numbers of Phox2b neurons were only observed in the retrotrapezoid nucleus of PD-OVX rats. Concerning respiratory parameters, in OVX rats, the resting and hypercapnia-induced tidal volume (VT ) is reduced, and ventilation ( ) changes independently of 6-OHDA administration. Notably, there is a reduction in the number of retrotrapezoid nucleus Phox2b neurons and hypercapnia-induced respiratory changes in PD-OVX animals due to a 6-OHDA and OVX interaction. These results suggest a protective effect induced by ovarian hormones in neuroanatomical changes observed in a female experimental PD model.