Cognitive Impairment in Genetic Parkinson’s Disease

Cognitive impairment is common in idiopathic Parkinson’s disease (PD). Knowledge of the contribution of genetics to cognition in PD is increasing in the last decades. Monogenic forms of genetic PD show distinct cognitive profiles and rate of cognitive decline progression. Cognitive impairment is higher in GBA- and SNCA-associated PD, lower in Parkin- and PINK1-PD, and possibly milder in LRRK2-PD. In this review, we summarize data regarding cognitive function on clinical studies, neuroimaging, and biological markers of cognitive decline in autosomal dominant PD linked to mutations in LRRK2 and SNCA, autosomal recessive PD linked to Parkin and PINK1, and also PD linked to GBA mutations.

Lee Silverman Voice Treatment to Improve Speech in Parkinson’s Disease: A Systemic Review and Meta-Analysis

Background. Speech changes occur in the early stages of Parkinson’s disease (PD) and cause communication difficulties, leading to social isolation. Lee Silverman voice treatment (LSVT) is a speech therapy approach designed to improve patients’ language and voice capabilities. Objective. The effectiveness of the LSVT was compared with that of other speech interventions or no treatment to evaluate PD patients with dysarthria. Design. Systematic review with meta-analysis of randomized trials. Data Sources: PubMed, Embase, Cochrane Library, CNKI, and SinoMed library were searched from inception to December 2021 related to PD and LSVT. Method. Abstracts were screened and reviewed against the eligibility criteria (intervention group participants were PD assessed based on LSVT (LSVT Loud) and randomized control). Result. Ten randomized controlled trials were identified on speech symptoms in patients with PD. Compared with the respiratory therapy (RET) exercise, or no training group, a significant improvement was detected in the sound press level (SPL) after immediate treatment during the reading of vowel and rainbow passages and an increase in semitone standard deviation (STSD). Furthermore, the LSVT training significantly increased the participants’ scores on unified Parkinson’s disease rating scale (UPDRS-III) and speech intelligibility. Conclusion. This meta-analysis demonstrated the efficacy of LSVT in increasing vocal loudness and functional communication among individuals with PD. However, most studies included participants with mild-moderate PD. Thus, additional randomized controlled trials (RCTs) with large sample sizes are needed to validate the efficacy of LSVT in patients with different progressions of PD, including severe PD.

Evaluation of Motor Complications in Parkinson’s Disease: Understanding the Perception Gap between Patients and Physicians

Background. Patients with Parkinson’s disease (PD) receiving levodopa treatment often report motor complications including wearing-off (WO), dyskinesia, and morning akinesia. As motor complications are associated with a decrease in patients’ quality of life (QoL), it is important to identify their occurrence and commence immediate management. This study investigated whether differences in the perception of motor complications exist between patients and their physicians in routine clinical practice. Methods. After an Internet-based screening survey, questionnaires were distributed to physicians and their patients in Japan. The 9-item Wearing-Off Questionnaire (WOQ-9) was used to objectively assess the presence of WO; patients with WOQ-9 scores ≥2 were considered to have WO. McNemar’s test was used to compare physician assessment versus WOQ-9 scores, patient self-awareness versus physician assessment, and patient self-awareness versus WOQ-9, separately. Morning akinesia and dyskinesia were assessed by both physician assessment and patient self-awareness with McNemar’s test. QoL was assessed using the 8-item Parkinson’s Disease Questionnaire (PDQ-8) with the Wilcoxon rank-sum test. Results. A total of 235 patients with PD and their 92 physicians participated in this survey. A significant discordance was observed between the WOQ-9 and physician assessment of WO (67.2% vs 46.0%; p < 0.0001 ). Furthermore, patient self-awareness of WO was 35.3% ( p = 0.0004 , vs physician). Morning akinesia (patient, 58.7%; physician, 48.9%; p = 0.0032 ), dyskinesia (patient, 34.0%; physician, 23.4%; p = 0.0006 ), and bodily discomfort (patient, 25.0; physician, 0.0; p = 0.0102 ) of QoL were underrecognized by physicians. Conclusions. This study investigated differences in the perception of WO between patients with PD and their physicians in routine clinical practice and highlighted that patients have a low awareness of the symptoms of WO compared with physician assessments and WOQ-9. Conversely, morning akinesia, dyskinesia, and bodily discomfort were underrecognized by physicians.

Gender Was Associated with Depression but Not with Gastrointestinal Dysfunction in Patients with Parkinson’s Disease

Objective. To investigate the association between gender and gastrointestinal (GI) dysfunctions, as well as gender and other motor symptoms/nonmotor symptoms, in a sample of PD patients. Methods. 186 patients with PD were recruited into this study and divided into male PD group (M-PD) and female PD group (FM-PD). Demographic and PD-related clinical information of the participants were collected by the same neurologist. PD patients were objectively assessed by a spectrum of rating scales of motor symptoms and nonmotor symptoms (including GI dysfunctions). The data were analyzed by SPSS 20 statistical software. Results. Totally 95 cases (51.08%) were in the M-PD group and 91 cases (48.92%) in the FM-PD group. There were no significant differences in age, BMI, and lifestyles between the two groups (P > 0.05). Males had higher educational level (P = 0.002). Females were more likely to have early satiety and loss of appetite (P = 0.025, P = 0.001). There were no significant differences in LED disease duration, age of motor symptoms onset, types of motor symptoms onset, location of motor symptoms onset, and phenotype of motor symptoms between the two groups (P > 0.05). Females had significantly higher UPDRS-III and HAMD scores than males (P = 0.037, P = 0.034). There were no significant differences in PQSI, ESS, RLS, RBD, HAMA, HAMD, and MoCA scores between the two groups. Gender was associated with HAMD (OR = 0.682, P = 0.019). Conclusions. Gender is a risk factor for depression, but not for GI dysfunctions in patients with PD.

Influence of N6-Methyladenosine Modification Gene HNRNPC on Cell Phenotype in Parkinson’s Disease

This study aimed to explore the N6-methyladenosine (m6A) modification genes involved in the pathogenesis of Parkinson’s disease (PD) through data analysis of the two data sets GSE120306 and GSE22491 in the GEO database and further explore its influence on cell phenotype in PD. We analyzed the differentially expressed genes and function enrichment analysis of the two sets of data and found that the expression of the m6A-modification gene HNRNPC was significantly downregulated in the PD group, and it played an important role in DNA metabolism, RNA metabolism, and RNA processing and may be involved in PD. Then, we constructed the HNRNPC differential expression cell line to study the role of this gene in the pathogenesis of PD. The results showed that overexpression of HNRNPC can promote the proliferation of PC12 cells, inhibit their apoptosis, and inhibit the expression of inflammatory factors IFN-β, IL-6, and TNF-α, suggesting that HNRNPC may cause PD by inhibiting the proliferation of dopaminergic nerve cells, promoting their apoptosis, and causing immune inflammation. Our study also has certain limitations. For example, the data of the experimental group and the validation group come from different cell types, and the data of the experimental group involve individuals with G2019S LRRK2 mutations. In addition, due to the low expression of HNRNPC in PC12 cells, we used the method of overexpressing this gene to study its function. All these factors may cause our conclusions to be biased. Therefore, more research is still needed to corroborate it in the future.

Validity and Reliability of the Persian Version of Parkinson’s Disease Sleep Scale-2

Objective. Sleep problems are nonmotor symptoms in Parkinson’s disease that should be carefully evaluated for better management and treatment. Parkinson’s Disease Sleep Scale (PDSS-2) is one of the most reliable tools for measuring sleep difficulties in people with Parkinson’s disease. This study investigated the psychometric properties of the Persian version of PDSS-2. Methods. Four hundred and fifty-six people with Parkinson’s disease with a mean age ±standard deviation of 60.7 ± 11.3 years were engaged in this study. Acceptability was assessed by floor and ceiling effects. Dimensionality was measured by exploratory factor analysis. The convergent validity of PDSS-2 with the Hospital Anxiety and Depression Scale (HADS) was assessed. Internal consistency and test-retest reliability were assessed with Cronbach’s alpha and intraclass correlation coefficient (ICC), respectively. Results. No noticeable ceiling and floor effect was detected. The dimensionality analysis showed three factors. A high correlation was obtained between PDSS-2 and HADS (anxiety subscale). Excellent internal consistency with α = 0.94, and good test-retest reliability with ICC = 0.89 were obtained. Conclusion. This study showed that the Persian version of Parkinson’s Disease Sleep Scale has acceptable validity and reliability for measuring sleep disturbances in people with Parkinson’s disease.

Correlation of Dopaminergic Denervation and the Progression of Autonomic Dysfunctions in Different Clinical Subtypes of Parkinson’s Disease

Background. Autonomic dysfunctions occur in the early stage of Parkinson’s disease (PD) and impact the quality of life during the progression of the disease. In this study, we evaluated the serial progression of autonomic dysfunctions between different subtypes of a prospective PD cohort. Materials and Methods. From the Parkinson’s Progression Markers Initiative (PPMI) database, 325 PD patients (age: 61.2 ± 9.7, M : F = 215 : 110) were enrolled. Patients were subgrouped into tremor-dominant (TD), indeterminate, and postural instability and gait disorder (PIGD) subtypes. The progression of autonomic dysfunctions and dopaminergic denervation from I-123 FP-CIT SPECT images of each group were analyzed and compared at baseline, 12 months, 24 months, and 48 months of follow-up periods. Results. The SCOPA-AUT score of the indeterminate subtype was significantly higher than that of the TD subtype ( P < 0.05 ) at baseline and was significantly higher than that of both TD and PIGD subtypes ( P < 0.05 ) at 48 months. The indeterminate subtype had the most significant correlation between the aggravation of dopaminergic denervation in I-123 FP-CIT SPECT images and the increase of SCOPA-AUT scores during 48 months of follow-up (r = 0.56, P < 0.01 ). Conclusions. Autonomic dysfunctions were most severe in the indeterminate subtype throughout the 48 months of the follow-up period, with a significant correlation with dopaminergic denervation. We suggest a positive relationship between dopaminergic denervation and autonomic dysfunctions of the indeterminate subtype, beginning from the early stage of PD.

Therapeutic Potential of α-Synuclein Evolvability for Autosomal Recessive Parkinson’s Disease

The majority of Parkinson’s disease (PD) is sporadic in elderly and is characterized by α-synuclein (αS) aggregation and other alterations involving mitochondria, ubiquitin-proteasome, and autophagy. The remaining are familial PD associated with gene mutations of either autosomal dominant or recessive inheritances. However, the former ones are similar to sporadic PD, and the latter ones are accompanied by impaired mitophagy during the reproductive stage. Since no radical therapies are available for PD, the objective of this paper is to discuss a mechanistic role for amyloidogenic evolvability, a putative physiological function of αS, among PD subtypes, and the potential relevance to therapy. Presumably, αS evolvability might benefit familial PD due to autosomal dominant genes and also sporadic PD during reproduction, which may manifest as neurodegenerative diseases through antagonistic pleiotropy mechanism in aging. Indeed, there are some reports describing that αS prevents apoptosis and mitochondrial alteration under the oxidative stress conditions, notwithstanding myriads of papers on the neuropathology of αS. Importantly, β-synuclein (βS), the nonamyloidogenic homologue of αS, might buffer against evolvability of αS protofibrils associated with neurotoxicity. Finally, it is intriguing to predict that increased αS evolvability through suppression of βS expression might protect against autosomal recessive PD. Collectively, further studies are warranted to better understand αS evolvability in PD pathogenesis, leading to rational therapy development.

Movement Disorders Associated with COVID-19

As neurological complications associated with COVID-19 keep unfolding, the number of cases with COVID-19-associated de novo movement disorders is rising. Although no clear pathomechanistic explanation is provided yet, the growing number of these cases is somewhat alarming. This review gathers information from 64 reports of de novo movement disorders developing after/during infection with SARS-CoV-2. Three new cases with myoclonus occurring shortly after a COVID-19 infection are also presented. Treatment resulted in partial to complete recovery in all three cases. Although the overall percentage of COVID-19 patients who develop movement disorders is marginal, explanations on a probable causal link have been suggested by numerous reports; most commonly involving immune-mediated and postinfectious and less frequently hypoxic-associated and ischemic-related pathways. The current body of evidence points myoclonus and ataxia out as the most frequent movement disorders occurring in COVID-19 patients. Some cases of tremor, chorea, and hypokinetic-rigid syndrome have also been observed in association with COVID-19. In particular, parkinsonism may be of dual concern in the setting of COVID-19; some have linked viral infections with Parkinson’s disease (PD) based on results from cerebrospinal fluid analyses, and PD is speculated to impact the outcome of COVID-19 in patients negatively. In conclusion, the present paper reviewed the demographic, clinical, and treatment-associated information on de novo movement disorders in COVID-19 patients in detail; it also underlined the higher incidence of myoclonus and ataxia associated with COVID-19 than other movement disorders.

Evaluation of Patients with Parkinson’s Disease in Intensive Care Units: A Cohort Study

Background. Parkinson’s disease affects approximately 1% of the worldwide population older than 60 years. This number is estimated to double by 2030, increasing the global burden of the disease. Patients with Parkinson’s disease are hospitalized 1.5 times more frequently and for longer periods than those without the disease, increasing health-related costs. Objective. To compare the characteristics and outcome of patients with and without Parkinson’s disease admitted to intensive care units (ICUs). Methods. Historical cohort study of ICU admissions in a Brazilian city over 18 years. All patients with Parkinson’s disease identified were matched for age, sex, year, and place of hospitalization with patients without the disease randomly selected from the same database. Results. The study included 231 patients with Parkinson’s disease (PD group) and 462 controls without the disease (NPD group). Compared with patients in the NPD group, those in the PD group were more frequently admitted with lower level of consciousness and increased APACHE II severity score but required less frequently vasoactive drugs. In total, 42.4% of the patients in the PD group were admitted to the ICUs due to sepsis or trauma. Although these patients had longer hospital stay, the mortality rates were comparable between groups. Parkinson’s disease was not associated with mortality, even when controlled for associated factors of disease severity. Conclusion. Although patients with Parkinson’s disease were admitted with higher severity scores and remained in the ICU for a longer time, their mortality rate was not higher than that in patients without the disease.