Bridging the Gap: A Comparative Analysis of Healthcare Quality Perceptions Between the Older People and Healthcare Providers.

In our study aimed at improving the healthcare system for the aging population, we compared healthcare quality evaluations between 96 older individuals and 30 healthcare providers in Split-Dalmatia County (Croatia). Using nonparametric analyses such as the Mann-Whitney and Wilcoxon tests on Likert scale questionnaire scores, we found most participants highlighted challenges such as healthcare affordability, long wait times, reliance on private care, poor public transportation, and insufficient rural healthcare services. Healthcare providers rated these quality indicators even more negatively. Both groups rated healthcare for dementia patients notably lower, while emergency response, treatment quality, and hospitalization ease were generally rated positively. The heightened awareness among healthcare providers raises the question: why is there a significant delay between recognizing these problems and implementing effective solutions to address them?

A case of corticobasal syndrome possibly associated with anti-Yo antibodies.

INTRODUCTION: Corticobasal syndrome (CBS) is a rare form of atypical parkinsonism, most commonly caused by neurodegenerative disorders. Autoimmune underlying conditions are extremely rare, and anti-Yo antibody-associated CBS has not been reported yet. CASE REPORT: Herein, we describe a case of a 68-year-old woman presenting with progressive dysarthria, gait instability and difficulty using her left hand with subacute deterioration during the last 3 months. Neurological examination revealed asymmetrical parkinsonism and pyramidal syndrome, reflex myoclonus and dystonia of her left upper limb, accompanied by apraxia of her left lower limb, fulfilling the criteria for possible CBS. Neuroimaging showed asymmetric frontoparietal atrophy, while cerebrospinal fluid and dopamine transporter imaging were normal. Prior to our evaluation, antineuronal autoantibody testing indicated positive anti-Yo antibodies. There was mild improvement after second IVIG cycle, and further investigation revealed no tumor. CONCLUSION: Although autoimmune etiology of this case cannot be certain, it highlights the potential expansion of the clinical spectrum of anti-Yo-associated paraneoplastic syndrome.

Precision Dopaminergic Treatment in a Cohort of Parkinson's Disease Patients Carrying Autosomal Recessive Gene Variants: Clinical Cohort Data and a Mini Review.

INTRODUCTION: Parkinson's disease (PD) patients harboring recessive gene variants exhibit a distinct clinical phenotype with an early disease onset and relatively mild symptoms. Data concerning individualized therapy for autosomal recessive PD forms are still scarce. METHODS: Demographic and treatment data of a cohort of PD carriers of recessive genes (nine homozygous or compound heterozygous PRKN carriers, four heterozygous PRKN carriers, and three biallelic PINK1 carriers) were evaluated. RESULTS: The average levodopa equivalent daily dose (LEDD) was 806.8 ± 453.5 (range 152-1810) in PRKN carriers and 765 ± 96.6 (range 660-850) in PINK1 carriers. The majority responded to low/moderate doses of levodopa. The response to dopamine agonists (DAs) was often favorable both as initial and longitudinal therapy. In total, 8/13 PRKN and 1/3 PINK1 carriers were treated with amantadine successfully, and this also applied to patients who could not tolerate levodopa or DAs. CONCLUSIONS: In the era of personalized treatment, the therapeutic approach in recessive PD gene carriers might differ as compared to idiopathic PD. Lower LEDD doses were efficient even in patients with a very long disease duration, while a few patients were doing well without any levodopa treatment decades after disease initiation. DAs or amantadine could be used as a first and main line treatment regimen if well tolerated. Literature data on therapeutic strategies in carriers of pathogenic mutations in recessive PD genes, including device-aided treatments, will be further discussed.

Unraveling the Potential Underlying Mechanisms of Mild Behavioral Impairment: Focusing on Amyloid and Tau Pathology.

The emergence of sustained neuropsychiatric symptoms (NPS) among non-demented individuals in later life, defined as mild behavioral impairment (MBI), is linked to a higher risk of cognitive decline. However, the underlying pathophysiological mechanisms remain largely unexplored. A growing body of evidence has shown that MBI is associated with alterations in structural and functional neuroimaging studies, higher genetic predisposition to clinical diagnosis of Alzheimer's disease (AD), as well as amyloid and tau pathology assessed in the blood, cerebrospinal fluid, positron-emission tomography (PET) imaging and neuropathological examination. These findings shed more light on the MBI-related potential neurobiological mechanisms, paving the way for the development of targeted pharmacological approaches. In this review, we aim to discuss the available clinical evidence on the role of amyloid and tau pathology in MBI and the potential underlying pathophysiological mechanisms. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, disruption of neurotrophic factors, such as the brain-derived neurotrophic factor (BDNF), abnormal neuroinflammatory responses including the kynurenine pathway, dysregulation of transforming growth factor beta (TGF-ß1), epigenetic alterations including micro-RNA (miR)-451a and miR-455-3p, synaptic dysfunction, imbalance in neurotransmitters including acetylcholine, dopamine, serotonin, gamma-aminobutyric acid (GABA) and norepinephrine, as well as altered locus coeruleus (LC) integrity are some of the potential mechanisms connecting MBI with amyloid and tau pathology. The elucidation of the underlying neurobiology of MBI would facilitate the design and efficacy of relative clinical trials, especially towards amyloid- or tau-related pathways. In addition, we provide insights for future research into our deeper understanding of its underlying pathophysiology of MBI, and discuss relative therapeutic implications.

Emerging Therapeutic Potential of Fluoxetine on Cognitive Decline in Alzheimer's Disease: Systematic Review.

Fluoxetine, a commonly prescribed medication for depression, has been studied in Alzheimer's disease (AD) patients for its effectiveness on cognitive symptoms. The aim of this systematic review is to investigate the therapeutic potential of fluoxetine in cognitive decline in AD, focusing on its anti-degenerative mechanisms of action and clinical implications. According to PRISMA, we searched MEDLINE, up to 1 April 2024, for animal and human studies examining the efficacy of fluoxetine with regard to the recovery of cognitive function in AD. Methodological quality was evaluated using the ARRIVE tool for animal AD studies and the Cochrane tool for clinical trials. In total, 22 studies were analyzed (19 animal AD studies and 3 clinical studies). Fluoxetine promoted neurogenesis and enhanced synaptic plasticity in preclinical models of AD, through a decrease in Aß pathology and increase in BDNF, by activating diverse pathways (such as the DAF-16-mediated, TGF-beta1, ILK-AKT-GSK3beta, and CREB/p-CREB/BDNF). In addition, fluoxetine has anti-inflammatory properties/antioxidant effects via targeting antioxidant Nrf2/HO-1 and hindering TLR4/NLRP3 inflammasome. Only three clinical studies showed that fluoxetine ameliorated the cognitive performance of people with AD; however, several methodological issues limited the generalizability of these results. Overall, the high-quality preclinical evidence suggests that fluoxetine may have neuroprotective, antioxidant, and anti-inflammatory effects in AD animal models. While more high-quality clinical research is needed to fully understand the mechanisms underlying these effects, fluoxetine is a promising potential treatment for AD patients. If future clinical trials confirm its anti-degenerative and neuroprotective effects, fluoxetine could offer a new therapeutic approach for slowing down the progression of AD.

Harnessing Therapeutic Potentials of Biochanin A in Neurological Disorders: Pharmacokinetic and Pharmacodynamic Overview.

Biochanin A, an isoflavone flavonoid with estrogenic activity, is naturally found in red clover and other legumes. It possesses a wide range of pharmacological properties, including antioxidant, anti-inflammatory, anti-apoptotic, neuroprotective, and anticancer effects. In recent years, a growing body of pre-clinical research has focused on exploring the therapeutic potential of biochanin A in various neurological disorders, such as Alzheimer's and Parkinson's disease, multiple sclerosis, epilepsy, ischemic brain injury, gliomas, and neurotoxicity. This comprehensive review aims to shed light on the underlying molecular mechanisms that contribute to the neuroprotective role of biochanin A based on previous pre-clinical studies. Furthermore, it provides a detailed overview of the protective effects of biochanin A in diverse neurological disorders. The review also addresses the limitations associated with biochanin A administration and discusses different approaches employed to overcome these challenges. Finally, it highlights the future opportunities for translating biochanin A from pre-clinical research to clinical studies while also considering its commercial viability as a dietary supplement or a potential treatment for various diseases.

Neurological Examination via Telemedicine: An Updated Review Focusing on Movement Disorders.

Patients with movement disorders such as Parkinson's disease (PD) living in remote and underserved areas often have limited access to specialized healthcare, while the feasibility and reliability of the video-based examination remains unclear. The aim of this narrative review is to examine which parts of remote neurological assessment are feasible and reliable in movement disorders. Clinical studies have demonstrated that most parts of the video-based neurological examination are feasible, even in the absence of a third party, including stance and gait-if an assistive device is not required-bradykinesia, tremor, dystonia, some ocular mobility parts, coordination, and gross muscle power and sensation assessment. Technical issues (video quality, internet connection, camera placement) might affect bradykinesia and tremor evaluation, especially in mild cases, possibly due to their rhythmic nature. Rigidity, postural instability and deep tendon reflexes cannot be remotely performed unless a trained healthcare professional is present. A modified version of incomplete Unified Parkinson's Disease Rating Scale (UPDRS)-III and a related equation lacking rigidity and pull testing items can reliably predict total UPDRS-III. UPDRS-II, -IV, Timed "Up and Go", and non-motor and quality of life scales can be administered remotely, while the remote Movement Disorder Society (MDS)-UPDRS-III requires further investigation. In conclusion, most parts of neurological examination can be performed virtually in PD, except for rigidity and postural instability, while technical issues might affect the assessment of mild bradykinesia and tremor. The combined use of wearable devices may at least partially compensate for these challenges in the future.

Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer's Disease.

The clinical features and pathophysiology of neuropsychiatric symptoms (NPSs) in dementia have been extensively studied. However, the genetic architecture and underlying neurobiological mechanisms of NPSs at preclinical stages of cognitive decline and Alzheimer's disease (AD) remain largely unknown. Mild behavioral impairment (MBI) represents an at-risk state for incident cognitive impairment and is defined by the emergence of persistent NPSs among non-demented individuals in later life. These NPSs include affective dysregulation, decreased motivation, impulse dyscontrol, abnormal perception and thought content, and social inappropriateness. Accumulating evidence has recently begun to shed more light on the genetic background of MBI, focusing on its potential association with genetic factors related to AD. The Apolipoprotein E (APOE) genotype and the MS4A locus have been associated with affective dysregulation, ZCWPW1 with social inappropriateness and psychosis, BIN1 and EPHA1 with psychosis, and NME8 with apathy. The association between MBI and polygenic risk scores (PRSs) in terms of AD dementia has been also explored. Potential implicated mechanisms include neuroinflammation, synaptic dysfunction, epigenetic modifications, oxidative stress responses, proteosomal impairment, and abnormal immune responses. In this review, we summarize and critically discuss the available evidence on the genetic background of MBI with an emphasis on AD, aiming to gain insights into the potential underlying neurobiological mechanisms, which till now remain largely unexplored. In addition, we propose future areas of research in this emerging field, with the aim to better understand the molecular pathophysiology of MBI and its genetic links with cognitive decline.

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.

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.

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.

Functional Implications of Protein Arginine Methyltransferases (PRMTs) in Neurodegenerative Diseases.

During the aging of the global population, the prevalence of neurodegenerative diseases will be continuously growing. Although each disorder is characterized by disease-specific protein accumulations, several common pathophysiological mechanisms encompassing both genetic and environmental factors have been detected. Among them, protein arginine methyltransferases (PRMTs), which catalyze the methylation of arginine of various substrates, have been revealed to regulate several cellular mechanisms, including neuronal cell survival and excitability, axonal transport, synaptic maturation, and myelination. Emerging evidence highlights their critical involvement in the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) spectrum, Huntington's disease (HD), spinal muscular atrophy (SMA) and spinal and bulbar muscular atrophy (SBMA). Underlying mechanisms include the regulation of gene transcription and RNA splicing, as well as their implication in various signaling pathways related to oxidative stress responses, apoptosis, neuroinflammation, vacuole degeneration, abnormal protein accumulation and neurotransmission. The targeting of PRMTs is a therapeutic approach initially developed against various forms of cancer but currently presents a novel potential strategy for neurodegenerative diseases. In this review, we discuss the accumulating evidence on the role of PRMTs in the pathophysiology of neurodegenerative diseases, enlightening their pathogenesis and stimulating future research.

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.

The Effects of a Single Session of a Rhythmic Movement Program on Selected Biopsychological Parameters in PD Patients: A Methodological Approach.

The aim of the present study is to examine the acute effects of a specially designed musicokinetic (MSK) program for patients with Parkinson's disease (PD) on (a) anxiety levels, (b) select kinematic and kinetic parameters, and (c) frontal cortex hemodynamic responses, during gait initiation and steady-state walking. Methods: This is a blind cross-over randomized control trial (RCT) in which 13 volunteers with PD will attend a 45 min MSK program under the following conditions: (a) a synchronous learning format and (b) an asynchronous remote video-based format. Changes in gait biomechanics and frontal cortex hemodynamic responses will be examined using a 10-camera 3D motion analysis (Vicon T-series, Oxford, UK), and a functional near-infrared spectroscopy (f-NIRS-Portalite, Artinis NL) system, respectively, while anxiety levels will be evaluated using the Hamilton Anxiety Rating Scale. Expected results: Guided by the rules of music, where periodicity is distinct, our specially designed MSK program may eventually be beneficial in improving motor difficulties and, hence, reducing anxiety. The combined implementation of f-NIRS in parallel with 3D gait analysis has yet to be evaluated in Parkinsonian patients following a MSK intervention. It is expected that the aforementioned intervention, through better rhythmicity, may improve the automatization of motor control, gait kinematics, and kinetics-supported by decreased frontal cortex hemodynamic activity-which may be linked to reduced anxiety levels.

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.

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.

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.