Role of microRNAs in cognitive decline related to COVID­19 (Review).

The likelihood and severity of cognitive decline related to coronavirus disease 2019 (COVID-19) have been shown to be reflected by the severity of the infection and concomitant alterations in specific biomarkers. The present review discusses the role of microRNAs (miRNAs/miRs) as biomarkers in COVID-19 and the potential molecular mechanisms of cognitive dysfunction related to COVID-19. A systematic search of published articles was carried out from January 31, 2000 to December 31, 2022 using the PubMed, ProQuest, Science Direct and Google Scholar databases, combining the following terms: 'COVID-19' OR 'SARS-CoV-2' OR 'post-COVID-19 effects' OR 'cognitive decline' OR 'neurodegeneration' OR 'microRNAs'. The quality of the evidence was evaluated as high, moderate, low, or very low based on the GRADE rating. A total of 36 studies were identified which demonstrated reduced blood levels of miR-146a, miR-155, Let-7b, miR 31 and miR-21 in patients with COVID-19 in comparison with a healthy group. The overexpression of the Let-7b may result in the downregulation of BCL-2 during COVID-9 by adjusting the immune responses between chronic inflammatory disease, type 2 diabetes, COVID-19 and cognitive impairment. The reduced expression of miR-31 is associated with cognitive dysfunction and increased microcoagulability in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). miR-155 mediates synaptic dysfunction and the dysregulation of neurotransmitters due to acute inflammation, leading to brain atrophy and a subcortical cognitive profile. The downregulation of miR-21 in patients with COVID-19 aggravates systemic inflammation, mediating an uncontrollable immune response and the failure of T-cell function, provoking cognitive impairment in patients with SARS-CoV-2. On the whole, the present review indicates that dysregulated levels of miR-146a, miR-155, Let-7b, miR-31, and miR-21 in the blood of individuals with COVID-19 are associated with cognitive decline, the chronic activation of immune mechanisms, the cytokine storm, and the vicious cycle of damage and systemic inflammation.

Some Novel Therapies in Parkinson's Disease: A Promising Path Forward or Not Yet? A Systematic Review of the Literature.

In light of the unsuccessful traditional therapies for Parkinson's disease (PD) overmany years, there is an unmet need for the development of novel therapies to alleviate the symptoms of PD retardation or halt the progression of the disease itself. This systematic review aims to critically update some of the most promising novel treatments including gene therapy, cell-based therapies, targeted drug delivery, and neuroprotective agents, focusing on their challenges, limitations and future directions in PD research. Gene therapy in PD is encouraging, with AAV-based approaches targeting neurotrophic factors, dopamine production, and neuronal circuits in animal and clinical trials. A promising approach to targeted drug delivery for PD involves the use of nanotechnology to create drug delivery vehicles that can traverse the blood-brain barrier and deliver medications specifically to the regions of the brain affected by PD. Neuroprotective agents are compounds that have the ability to protect neurons from degeneration and death, and they hold great promise for the evolution of disease-modifying treatments for PD. Magnetic field therapy is a promising non-invasive method that promotes neural plasticity in PD. The establishment of standardized protocols for animal and human studies, safety, ethical considerations, and cost-effectiveness are the major challenges for the future research of novel PD therapies. The development of novel therapies for PD represents a promising path toward to effective personalized disease-modifying treatments for PD.

Non-Motor Disorders in Parkinson Disease and Other Parkinsonian Syndromes.

Parkinsonism is an umbrella term that refers to multisystemic neurodegenerative disorders characterized by a broad spectrum of motor and non-motor symptoms (NMSs) [...].

Mild Behavioral Impairment in Parkinson's Disease: An Updated Review on the Clinical, Genetic, Neuroanatomical, and Pathophysiological Aspects.

Neuropsychiatric symptoms (NPS), including depression, anxiety, apathy, visual hallucinations, and impulse control disorders, are very common during the course of Parkinson's disease (PD), occurring even at the prodromal and premotor stages. Mild behavioral impairment (MBI) represents a recently described neurobehavioral syndrome, characterized by the emergence of persistent and impactful NPS in later life, reflecting arisk of dementia. Accumulating evidence suggests that MBI is highly prevalent in non-demented patients with PD, also being associated with an advanced disease stage, more severe motor deficits, as well as global and multiple-domain cognitive impairment. Neuroimaging studies have revealed that MBI in patients with PD may be related todistinct patterns of brain atrophy, altered neuronal connectivity, and distribution of dopamine transporter (DAT) depletion, shedding more light on its pathophysiological background. Genetic studies in PD patients have also shown that specific single-nucleotide polymorphisms (SNPs) may be associated with MBI, paving the way for future research in this field. In this review, we summarize and critically discuss the emerging evidence on the frequency, associated clinical and genetic factors, as well as neuroanatomical and neurophysiological correlates of MBI in PD, aiming to elucidate the underlying pathophysiology and its potential role as an early "marker" of cognitive decline, particularly in this population. In addition, we aim to identify research gaps, and propose novel relative areas of interest that could aid in our better understanding of the relationship of this newly defined diagnostic entity with PD.

Frequency of Impulsive-Compulsive Behavior and Associated Psychological Factors in Parkinson's Disease: Lack of Control or Too Much of It?

Background and Objectives: Impulse Control Disorders (ICDs) including pathological gambling, hypersexuality, compulsive eating, compulsive buying, and other related behaviors are well-known distinct non-motor symptoms in Parkinson's Disease (PD). Some large-scale studies present a prevalence of at least 10%, however, there are other reports providing much higher rates. The majority of the conducted studies investigating ICDs focus mainly on pharmacological factors, however, from a psychological perspective, there is yet enough room for investigation. In order to address the above issues, we designed a two-part study. Materials and Methods: First, we aimed to identify the incidence of ICD and related behaviors in a cohort of 892 Greek PD patients. Second, we administered a comprehensive battery of psychometric tools to assess psychological factors such as personality dimensions, quality of life, defenses, coherence, and resilience as well as to screen general cognitive capacity in PD patients with ICD manifestations. Results: With regard to the first part, we identified ICD manifestations in 12.4% of the patients. Preliminary findings from the second part indicate elevated activity, rather than impulsivity, as well as interrelations between several variables, including measures of activity, coping mechanisms, and quality of life. Conclusions: We present a working hypothesis for the contribution of high activity channeled to specific behavioral patterns through specific coping mechanisms, concerning the emergence of ICDs and related behaviors in PD, and further stress the importance of compulsivity rather than impulsivity in this process.

The Landscape of Monogenic Parkinson's Disease in Populations of Non-European Ancestry: A Narrative Review.

INTRODUCTION: There has been a bias in the existing literature on Parkinson's disease (PD) genetics as most studies involved patients of European ancestry, mostly in Europe and North America. Our target was to review published research data on the genetic profile of PD patients of non-European or mixed ancestry. METHODS: We reviewed articles published during the 2000-2023 period, focusing on the genetic status of PD patients of non-European origin (Indian, East and Central Asian, Latin American, sub-Saharan African and Pacific islands). RESULTS: There were substantial differences regarding monogenic PD forms between patients of European and non-European ancestry. The G2019S Leucine Rich Repeat Kinase 2 (LRRK2) mutation was rather scarce in non-European populations. In contrast, East Asian patients carried different mutations like p.I2020T, which is common in Japan. Parkin (PRKN) variants had a global distribution, being common in early-onset PD in Indians, in East Asians, and in early-onset Mexicans. Furthermore, they were occasionally present in Black African PD patients. PTEN-induced kinase 1 (PINK1) and PD protein 7 (DJ-1) variants were described in Indian, East Asian and Pacific Islands populations. Glucocerebrosidase gene variants (GBA1), which represent an important predisposing factor for PD, were found in East and Southeast Asian and Indian populations. Different GBA1 variants have been reported in Black African populations and Latin Americans. CONCLUSIONS: Existing data reveal a pronounced heterogeneity in the genetic background of PD. A number of common variants in populations of European ancestry appeared to be absent or scarce in patients of diverse ethnic backgrounds. Large-scale studies that include genetic screening in African, Asian or Latin American populations are underway. The outcomes of such efforts will facilitate further clinical studies and will possibly contribute to the identification of either new pathogenic mutations in already described genes or novel PD-related genes.

Cognitive Impairment in Parkinson's Disease: An Updated Overview Focusing on Emerging Pharmaceutical Treatment Approaches.

Cognitive impairment in patients with Parkinson's disease (PD) is one of the commonest and most disabling non-motor manifestations during the course of the disease. The clinical spectrum of PD-related cognitive impairment includes subjective cognitive decline (SCD), mild cognitive impairment (MCI) and PD dementia (PDD). As the disease progresses, cognitive decline creates a significant burden for the family members and/or caregivers of patients with PD, and has a great impact on quality of life. Current pharmacological treatments have demonstrated partial efficacy and failed to halt disease progression, and novel, effective, and safe therapeutic strategies are required. Accumulating preclinical and clinical evidence shows that several agents may provide beneficial effects on patients with PD and cognitive impairment, including ceftriaxone, ambroxol, intranasal insulin, nilotinib, atomoxetine, mevidalen, blarcamesine, prasinezumab, SYN120, ENT-01, NYX-458, GRF6021, fosgonimeton, INT-777, Neuropeptide S, silibinin, osmotin, cordycepin, huperzine A, fibroblast growth factor 21, Poloxamer 188, ginsenoside Rb1, thioredoxin-1, tangeretin, istradefylline and Eugenia uniflora. Potential underlying mechanisms include the inhibition of a-synuclein aggregation, the improvement of mitochondrial function, the regulation of synaptic plasticity, an impact on the gut-brain axis, the modulation of neuroinflammation and the upregulation of neurotrophic factors, as well as cholinergic, dopaminergic, serotoninergic and norepinephrine neurotransmission. In this updated overview, we aim to cover the clinical aspects of the spectrum of PD-related cognitive impairment and discuss recent evidence on emerging treatment approaches that are under investigation at a preclinical and clinical level. Finally, we aim to provide additional insights and propose new ideas for investigation that may be feasible and effective for the spectrum of PD-related cognitive impairment.

Comprehensive Evaluation of Psychotic Features and Their Clinical Correlates in Early Parkinson's Disease.

BACKGROUND: Some reports suggest that psychotic features may occur in the early stages of Parkinson's disease (PD), but sensitive tools have not been utilized. OBJECTIVE: The aim was to evaluate the presence of psychotic symptoms using detailed scales and to assess the association with clinical characteristics. METHODS: Healthy controls and patients within three years of PD onset were recruited. Participants were examined for psychotic symptoms using two different instruments: the Comprehensive Assessment of At-Risk Mental States (CAARMS) and a 10 question PD specific psychosis severity scale (10PDQ). In the PD group, medication use, motor and non-motor symptoms were documented. RESULTS: Based on CAARMS and 10PDQ scales, psychotic features were present in 39% (27/70) of patients and 4% (3/74) of controls. The prevalence of passage hallucinations and illusions was significantly higher in PD compared to the control group. The presence of PD-associated psychotic features was not significantly affected by medication, motor severity or global cognitive status. Higher prevalence of overall non-motor manifestations, REM sleep behavior disorder (RBD) and depressive symptoms was significantly associated with the manifestation of psychotic features in PD [(adjusted OR:1.3; 95% CI:1.1-1.6; p = 0.003), (adjusted OR:1.3; 95% CI:1.0-1.6; p = 0.023), and (adjusted OR:1.2; 95% CI:1.0-1.4;p = 0.026)]. CONCLUSIONS: Psychotic phenomena mainly of minor nature are highly common in early PD. Cumulative non-motor symptoms, RBD and depressive features are associated with the presence of psychotic symptoms in this non-demented, early-stage PD population. More studies are needed to clarify the mechanisms that contribute to the onset of psychotic features in early PD.

Monitoring and Predicting Health Status in Neurological Patients: The ALAMEDA Data Collection Protocol.

(1) Objective: We explore the predictive power of a novel stream of patient data, combining wearable devices and patient reported outcomes (PROs), using an AI-first approach to classify the health status of Parkinson's disease (PD), multiple sclerosis (MS) and stroke patients (collectively named PMSS). (2) Background: Recent studies acknowledge the burden of neurological disorders on patients and on the healthcare systems managing them. To address this, effort is invested in the digital transformation of health provisioning for PMSS patients. (3) Methods: We introduce the data collection journey within the ALAMEDA project, which continuously collects PRO data for a year through mobile applications and supplements them with data from minimally intrusive wearable devices (accelerometer bracelet, IMU sensor belt, ground force measuring insoles, and sleep mattress) worn for 1-2 weeks at each milestone. We present the data collection schedule and its feasibility, the mapping of medical predictor variables to wearable device capabilities and mobile application functionality. (4) Results: A novel combination of wearable devices and smartphone applications required for the desired analysis of motor, sleep, emotional and quality-of-life outcomes is introduced. AI-first analysis methods are presented that aim to uncover the prediction capability of diverse longitudinal and cross-sectional setups (in terms of standard medical test targets). Mobile application development and usage schedule facilitates the retention of patient engagement and compliance with the study protocol.

microRNA and circRNA in Parkinson's Disease and atypical parkinsonian syndromes.

Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) are atypical parkinsonian syndromes (APS) with various clinical phenotypes and considerable clinical overlap with idiopathic Parkinson's disease (iPD). This disease heterogeneity makes ante-mortem diagnosis extremely challenging with up to 24% of patients misdiagnosed. Because diagnosis is predominantly clinical, there is great interest in identifying biomarkers for early diagnosis and differentiation of the different types of parkinsonism. Compared to protein biomarkers, microRNAs (miRNAs) and circularRNAs (circRNAs) are stable tissue-specific molecules that can be accurately measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). This chapter critically reviews miRNAs and circRNAs as diagnostic biomarkers and therapeutics to differentiate atypical parkinsonian disorders and their role in disease pathogenesis.

Double Trouble: Association of Malignant Melanoma with Sporadic and Genetic Forms of Parkinson's Disease and Asymptomatic Carriers of Related Genes: A Brief Report.

Introduction: Previous epidemiological evidence has established the co-occurrence of malignant melanoma (MM) and Parkinson's disease (PD). Shared molecular mechanisms have been proposed to be implicated in this relationship. The aim of the present study was to assess the prevalence of MM in patients with sporadic and genetic types of PD, as well as in asymptomatic carriers of PD-related genes. Methods: Data regarding past medical history and concomitant disease of 1416 patients with PD (including 20 participants with prodromal disease who phenoconverted to PD), 275 healthy controls (HCs) and 670 asymptomatic carriers of PD-related genes were obtained from the database of the Parkinson's Progression Markers Initiative (PPMI). Focus was placed on information about a medical record of MM. We also retrieved data regarding the genetic status of selected PPMI participants with a positive MM history. Results: In total, 46 patients with PD reported a positive MM history. Concerning the genetic forms of PD, nine of these PD patients (2.47%) carried a Leucine Rich Repeat Kinase 2 (LRRK2) gene mutation (mainly the G2019S), while eight (4.49%) harbored a Glucocerebrosidase (GBA) gene mutation (mainly the N370S). No alpha-synuclein (SNCA) gene mutation was identified in patients with an MM history. The remaining 29 PD patients (3.5%) were genetically undetermined. In total, 18 asymptomatic carriers of PD-related genes had a positive medical history for MM: among them, 10 carried an LRRK2 gene mutation (2.69%) and 10 a GBA gene mutation (3.51%) (2 were dual carriers). MM history was identified for seven HCs (2.5%). Conclusions: We replicated the previously reported association between genetically undetermined PD (GU-PD) and MM. A correlation of LRRK2 mutations with the development of MM could not be verified in either symptomatic PD patients or asymptomatic carriers, implicating distinct pathogenetic mechanisms as compared to GU-PD. Importantly, despite the limited literature evidence on Gaucher disease, this study highlights for the first time the relatively high prevalence of MM among asymptomatic and symptomatic PD GBA mutation carriers, with potential clinical implications.

Pharmacological and Non-Pharmacological Treatments for Depression in Parkinson's Disease: An Updated Review.

Depression represents one of the most common non-motor disorders in Parkinson's disease (PD) and it has been related to worse life quality, higher levels of disability, and cognitive impairment, thereby majorly affecting not only the patients but also their caregivers. Available pharmacological therapeutic options for depression in PD mainly include selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and tricyclic antidepressants; meanwhile, agents acting on dopaminergic pathways used for motor symptoms, such as levodopa, dopaminergic agonists, and monoamine oxidase B (MAO-B) inhibitors, may also provide beneficial antidepressant effects. Recently, there is a growing interest in non-pharmacological interventions, including cognitive behavioral therapy; physical exercise, including dance and mind-body exercises, such as yoga, tai chi, and qigong; acupuncture; therapeutic massage; music therapy; active therapy; repetitive transcranial magnetic stimulation (rTMS); and electroconvulsive therapy (ECT) for refractory cases. However, the optimal treatment approach for PD depression is uncertain, its management may be challenging, and definite guidelines are also lacking. It is still unclear which of these interventions is the most appropriate and for which PD stage under which circumstances. Herein, we aim to provide an updated comprehensive review of both pharmacological and non-pharmacological treatments for depression in PD, focusing on recent clinical trials, systematic reviews, and meta-analyses. Finally, we discuss the pharmacological agents that are currently under investigation at a clinical level, as well as future approaches based on the pathophysiological mechanisms underlying the onset of depression in PD.

Jumping to conclusions bias, psychosis and impulsivity in early stages of Parkinson's disease.

OBJECTIVES: The aim was to explore the correlations between Jumping to Conclusions (JtC) tendency and neuropsychiatric features in patients with early Parkinson's disease (PD). BACKGROUND: According to few reports, PD patients with impulsive-compulsive behaviors (ICBs) are prone to working memory difficulties including JtC bias. The correlation of psychotic features and JtC tendency remains still unclear. METHODS: Healthy controls and patients within 3 years of PD onset were recruited. Participants were examined for psychotic symptoms using a 10 question PD-specific psychosis severity scale. JtC was measured by a probalistic reasoning scenario (beads task). In PD group, medication use, motor and non-motor symptoms were documented. Impulsivity was evaluated using the Questionnaire for Impulsive-Compulsive Disorders in PD (QUIP). RESULTS: The prevalence of JtC bias was 9% (6/70) in healthy individuals, compared to 32% (22/68) of PD group [p = 0.001]. No association was detected between the presence of JtC tendency and PD-associated psychosis (p = 0.216). Patients with JtC had shorter duration of PD, more tremor-dominant PD subtype and higher QUIP scores, regardless of the dopaminergic therapy (p = 0.043, p = 0.015, p = 0.007, respectively). A trend towards attention and inhibition control deficit was noticed in JtC patients. CONCLUSIONS: We found a high prevalence of JtC bias in early, cognitively intact PD population and a potential link between subthreshold ICBs and poor performance on beads task. Additional studies are needed to confirm our results and elaborate on the mechanisms that correlate impulsivity with JtC tendency, which are likely to be different from those mediating psychotic features in early PD.

Characteristics and outcomes of elderly patients with Parkinson's disease hospitalized due to COVID­19­associated pneumonia.

Patients with Parkinson's disease (PD) and coronavirus disease 2019 (COVID-19)-associated pneumonia present, according to the literature, high mortality rates due to the nature of the disease, advanced age, and underlying diseases. Most available studies, however, refer to the first waves of the pandemic. The aim of the present study was to investigate the clinical characteristics and outcomes of elderly patients (≥65 years old) with PD hospitalized with COVID-19-associated pneumonia during the period of prevalence of various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, as well as to determine possible prognostic factors for poor outcomes. During the period from February 15, 2021, to July 15, 2022, 1,144 elderly patients with COVID-19 pneumonia were hospitalized. Age, sex, Charlson comorbidity index, vaccination status against SARS-CoV-2, and admission laboratory parameters were recorded for all patients. A total of 36 (3.1%) patients with PD were hospitalized due to COVID-19-associated pneumonia (18 males, 50%). The mean age of the patients was 82.72±8.18 years. In total, 8 patients (22.2%) were hospitalized during the period of alpha variant predominance, 3 patients (8.3%) during the period of delta variant predominance, and 25 patients (69.4%) during the omicron variant predominance period. Of note, 16 patients (44.4%) were vaccinated with at least two doses. In addition, 17 (47.2%) patients succumbed to the disease. Between the patients who survived and those who succumbed, a statistically significant difference was only found in the mean value of albumin (37.48±6.02 vs. 31.97±5.34 g/l, P=0.019). In particular, as shown by receiver operating characteristic curve analysis, albumin exhibited a satisfactory predictive ability for mortality (area under the curve, 0.780; P=0.013) with an albumin value ≤37.7 g/l being able to predict mortality with 85.7% sensitivity and 54.8% specificity. Overall, the findings of the present study indicate that mortality among elderly patients with PD hospitalized with COVID-19-associated pneumonia was high in all phases of the pandemic. A low albumin value, not only as an indicator of the immune status, but also of the nutritional status, is a predictor of adverse outcomes.

Serum Uric Acid as a Putative Biomarker in Prodromal Parkinson's Disease: Longitudinal Data from the PPMI Study.

BACKGROUND: The role of blood uric acid as a biomarker in symptomatic motor PD has been increasingly established in the literature. OBJECTIVE: Our present study assessed the role of serum uric acid as a putative biomarker in a prodromal PD cohort [REM Sleep Behavior disorder (RBD) and Hyposmia] followed longitudinally. METHODS: Longitudinal 5-year serum uric acid measurement data of 39 RBD patients and 26 Hyposmia patients with an abnormal DATSCAN imaging were downloaded from the Parkinson's Progression Markers Initiative database. These cohorts were compared with 423 de novo PD patients and 196 healthy controls enrolled in the same study. RESULTS: After adjusting for age, sex, body mass index, and concomitant disorders (hypertension/gout), baseline and longitudinal serum uric acid levels were higher in the RBD subgroup as compared to the established PD cohort (p = 0.004 and p = 0.001). (Baseline RBD 6.07±1.6 vs. Baseline PD 5.35±1.3 mg/dL and Year-5 RBD 5.7±1.3 vs. Year-5 PD 5.26±1.33). This was also true for longitudinal measurements in the Hyposmic subgroup (p = 0.008) (Baseline Hyposmic 5.7±1.6 vs. PD 5.35±1.3 mg/dL and Year-5 Hyposmic 5.58±1.6 vs. PD 5.26±1.33). CONCLUSION: Our results indicate that serum uric acid levels are higher in prodromal PD subjects with ongoing dopaminergic degeneration compared to those with manifest PD. These data indicate that the well-established decrease in the levels of serum uric acid occurs with the transition from prodromal to clinical PD. Whether the higher levels of serum uric acid observed in prodromal PD may provide protection against conversion to full-blown clinical PD will require further study.

Predictors of COVID­19­associated mortality among hospitalized elderly patients with dementia.

The mortality of elderly patients with dementia hospitalized with coronavirus disease 2019 (COVID-19)-associated pneumonia is high. The mortality rate of these patients continues to be high following their discharge. However, data on the outcomes of these patients in all phases of the pandemic are limited. The aim of the present study was to examine the clinical characteristics and the in-hospital and 90-day mortality rates of elderly patients with dementia hospitalized due to COVID-19-associated pneumonia during all phases of the pandemic. During the time period between February 15, 2021 to July 15, 2022, 105 elderly patients (≥65 years old) with dementia of various etiologies were hospitalized due to COVID-19-associated pneumonia. The patient characteristics and in-hospital outcomes within 90 days of admission were recorded. The mean age of the patients was 84.03±7.61 years and 60 (57.1%) patients were females. A total of 52 (49.5%) patients were hospitalized during the omicron variant period, 27 (25.7%) were fully vaccinated (three doses) and 38 (36.2%) patients succumbed during their hospitalization. In total, 52 (49.5%) patients succumbed within the first 90 days of admission. According to the univariate regression analysis, the omicron variant [hazard ratio (HR), 2.126; 95% confidence interval (CI), 1.073-4.213; P=0.031] and the absence of full vaccination (HR, 6.231; 95% CI, 1.500-25.87; P=0.012) were associated with a higher in-hospital mortality. In the multivariate regression analysis, only the absence of complete vaccination was an independent predictor of mortality (HR, 5.182; 95% CI, 1.205-22.28; P=0.027). According to the univariate regression analysis, age (HR, 1.045; 95% CI, 1.006-1.085; P=0.023) and the lack of complete vaccination (HR, 3.254; 95% CI, 1.294-8.181; P=0.012) were associated with 90-day mortality; in addition, by multivariate regression analysis, age (HR, 1.047; 95% CI, 1.007-1.048; P=0.021) and the absence of full vaccination (HR, 3.286; 95% CI, 1.307-8.265; P=0.011) exhibited an independent association with the 90-day mortality rate. Based on the findings presented herein, the in-hospital and 90-day mortality rates of elderly patients with dementia and COVID-19-associated pneumonia is high. An older age and the lack of complete vaccination are independently associated with poor outcomes.

Genetic Insights into the Molecular Pathophysiology of Depression in Parkinson's Disease.

Background and Objectives: Parkinson's disease (PD) is a clinically heterogeneous disorder with poorly understood pathological contributing factors. Depression presents one of the most frequent non-motor PD manifestations, and several genetic polymorphisms have been suggested that could affect the depression risk in PD. Therefore, in this review we have collected recent studies addressing the role of genetic factors in the development of depression in PD, aiming to gain insights into its molecular pathobiology and enable the future development of targeted and effective treatment strategies. Materials and Methods: we have searched PubMed and Scopus databases for peer-reviewed research articles published in English (pre-clinical and clinical studies as well as relevant reviews and meta-analyses) investigating the genetic architecture and pathophysiology of PD depression. Results: in particular, polymorphisms in genes related to the serotoninergic pathway (sodium-dependent serotonin transporter gene, SLC6A4, tryptophan hydrolase-2 gene, TPH2), dopamine metabolism and neurotransmission (dopamine receptor D3 gene, DRD3, aldehyde dehydrogenase 2 gene, ALDH2), neurotrophic factors (brain-derived neurotrophic factor gene, BDNF), endocannabinoid system (cannabinoid receptor gene, CNR1), circadian rhythm (thyrotroph embryonic factor gene, TEF), the sodium-dependent neutral amino acid transporter B(0)AT2 gene, SLC6A15), and PARK16 genetic locus were detected as altering susceptibility to depression among PD patients. However, polymorphisms in the dopamine transporter gene (SLC6A3), monoamine oxidase A (MAOA) and B (MAOB) genes, catechol-O-methyltransferase gene (COMT), CRY1, and CRY2 have not been related to PD depression. Conclusions: the specific mechanisms underlying the potential role of genetic diversity in PD depression are still under investigation, however, there is evidence that they may involve neurotransmitter imbalance, mitochondrial impairment, oxidative stress, and neuroinflammation, as well as the dysregulation of neurotrophic factors and their downstream signaling pathways.

New­onset non­motor symptoms in patients with Parkinson's disease and post­COVID­19 syndrome: A prospective cross­sectional study.

The clinical range of post-coronavirus disease 2019 (COVID-19) symptoms in patients with Parkinson's disease (PD) has not yet been thoroughly characterized, with the exception of a few small case studies. The aim of the present study was to investigate the motor and non-motor progression of patients with PD (PWP) and post-COVID-19 syndrome (PCS) at baseline and at 6 months after infection with COVID-19. A cross-sectional prospective study of 38 PWP+/PCS+ and 20 PWP+/PCS- matched for age, sex and disease duration was conducted. All patients were assessed at baseline and at 6 months using a structured clinicodemographic questionnaire, the Unified Parkinson's Disease Rating Scale Part III (the UPDRS III), the Montreal Cognitive Assessment, the Hoehn and Yahr scale, the Geriatric Depression Scale and the levodopa equivalent daily dose (LEDD). There was a statistically significant difference in the LEDD (P=0.039) and UPDRS III (P=0.001) at baseline and at 6 months after infection with COVID-19 between the PWP with PCS groups. The most common non-motor PCS symptoms were anosmia/hyposmia, sore throat, dysgeusia and skin rashes. There was no statistically significant difference in demographics or specific scores between the two groups, indicating that no prognostic factor for PCS in PWP could be identified. The novelty of the present study is that it suggests the new onset of non-motor PCS symptoms of PWP with a mild to moderate stage.

Mobile App Interventions for Parkinson's Disease, Multiple Sclerosis and Stroke: A Systematic Literature Review.

Central nervous system diseases (CNSDs) lead to significant disability worldwide. Mobile app interventions have recently shown the potential to facilitate monitoring and medical management of patients with CNSDs. In this direction, the characteristics of the mobile apps used in research studies and their level of clinical effectiveness need to be explored in order to advance the multidisciplinary research required in the field of mobile app interventions for CNSDs. A systematic review of mobile app interventions for three major CNSDs, i.e., Parkinson's disease (PD), multiple sclerosis (MS), and stroke, which impose significant burden on people and health care systems around the globe, is presented. A literature search in the bibliographic databases of PubMed and Scopus was performed. Identified studies were assessed in terms of quality, and synthesized according to target disease, mobile app characteristics, study design and outcomes. Overall, 21 studies were included in the review. A total of 3 studies targeted PD (14%), 4 studies targeted MS (19%), and 14 studies targeted stroke (67%). Most studies presented a weak-to-moderate methodological quality. Study samples were small, with 15 studies (71%) including less than 50 participants, and only 4 studies (19%) reporting a study duration of 6 months or more. The majority of the mobile apps focused on exercise and physical rehabilitation. In total, 16 studies (76%) reported positive outcomes related to physical activity and motor function, cognition, quality of life, and education, whereas 5 studies (24%) clearly reported no difference compared to usual care. Mobile app interventions are promising to improve outcomes concerning patient's physical activity, motor ability, cognition, quality of life and education for patients with PD, MS, and Stroke. However, rigorous studies are required to demonstrate robust evidence of their clinical effectiveness.