Parkin mRNA Expression Levels in Peripheral Blood Mononuclear Cells in Parkin-Related Parkinson's Disease.

INTRODUCTION: Pathogenic variants in parkin (PRKN gene) are the second most prevalent known monogenic cause of Parkinson's disease (PD). How monoallelic or biallelic pathogenic variants in the PRKN gene may affect its transcription in patient-derived biological material has not been systematically studied. METHODS: PRKN mRNA expression levels were measured with real-time polymerase chain reaction (RT-PCR) in peripheral blood mononuclear cells (PBMCs). PBMCs were derived from PRKN-mutated PD patients (PRKN-PD) (n = 12), sporadic PD (sPD) (n = 21) and healthy controls (n = 21). Six of the PRKN-PD patients were heterozygous, four were compound heterozygous, and two were homozygous for PRKN variants. RESULTS: A statistically significant decrease in PRKN expression levels was present, compared to healthy controls and sPD, in heterozygous (P = 0.019 and 0.031 respectively) and biallelic (P < 0.001 for both) PRKN-PD. PRKN expression levels in biallelic PD patients were uniformly very low and were reduced, albeit not significantly, compared to heterozygotes. Based on receiver operating characteristic analysis, low PRKN expression levels were a sensitive and extremely specific indicator for the presence of PRKN pathogenic variants. CONCLUSIONS: Assessment of PRKN mRNA levels in PBMCs may be a useful way to screen for biallelic pathogenic variants in the PRKN gene. Suspicion for certain variants in a heterozygous state may also be raised based on low PRKN mRNA levels. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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.

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.

Ambiental Factors in Parkinson's Disease Progression: A Systematic Review.

Background and Objectives: So far, there is little evidence of the ambient effect on motor and non-motor symptoms of Parkinson's Disease (PD). This systematic review aimed to determine the association between ambiental factors and the progression of PD. Materials and Methods: A systematic literature search of PubMed, Cochrane, Embase, and Web of Science was conducted up to 21 December 2021 according the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Eight articles were used in the analyses. Long-term exposure to fine particles (particulate matter ≤ 2.5 µm; PM2.5) was positively associated with disease aggravation in two studies. Short-term PM2.5 exposure was positively associated with disease aggravation in three studies. Significant associations were found between PD aggravation and NO2, SO2, CO, nitrate and organic matter (OM) concentrations in two studies. Associations were more pronounced, without reaching statistical significance however, in women, patients over 65 years old and cold temperatures. A 1% increase in temperature was associated with a significant 0.18% increase in Levodopa Equivalent Dose (LED). Ultraviolet light and humidity were not significantly associated with an increase in LED. There was no difference in hallucination severity with changing seasons. There was no evidence for seasonal fluctuation in Unified Parkinson's Disease Rating Scale (UPDRS) scores. Conclusions: There is a link between air pollutants and temperature for PD progression, but this has yet to be proven. More longitudinal studies are warranted to confirm these findings.

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.

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.

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.

How Telemedicine Can Improve the Quality of Care for Patients with Alzheimer's Disease and Related Dementias? A Narrative Review.

Background and Objectives: Dementia affects more than 55 million patients worldwide, with a significant societal, economic, and psychological impact. However, many patients with Alzheimer's disease (AD) and other related dementias have limited access to effective and individualized treatment. Care provision for dementia is often unequal, fragmented, and inefficient. The COVID-19 pandemic accelerated telemedicine use, which holds promising potential for addressing this important gap. In this narrative review, we aim to analyze and discuss how telemedicine can improve the quality of healthcare for AD and related dementias in a structured manner, based on the seven dimensions of healthcare quality defined by the World Health Organization (WHO), 2018: effectiveness, safety, people-centeredness, timeliness, equitability, integrated care, and efficiency. Materials and Methods: MEDLINE and Scopus databases were searched for peer-reviewed articles investigating the role of telemedicine in the quality of care for patients with dementia. A narrative synthesis was based on the seven WHO dimensions. Results: Most studies indicate that telemedicine is a valuable tool for AD and related dementias: it can improve effectiveness (better access to specialized care, accurate diagnosis, evidence-based treatment, avoidance of preventable hospitalizations), timeliness (reduction of waiting times and unnecessary transportation), patient-centeredness (personalized care for needs and values), safety (appropriate treatment, reduction of infection risk),integrated care (interdisciplinary approach through several dementia-related services), efficiency (mainly cost-effectiveness) and equitability (overcoming geographical barriers, cultural diversities). However, digital illiteracy, legal and organizational issues, as well as limited awareness, are significant potential barriers. Conclusions: Telemedicine may significantly improve all aspects of the quality of care for patients with dementia. However, future longitudinal studies with control groups including participants of a wide educational level spectrum will aid in our deeper understanding of the real impact of telemedicine in quality care for this population.

A Novel SNCA A30G Mutation Causes Familial Parkinson's Disease.

BACKGROUND: The SNCA gene encoding α-synuclein (αSyn) is the first gene identified to cause autosomal-dominant Parkinson's disease (PD). OBJECTIVE: We report the identification of a novel heterozygous A30G mutation of the SNCA gene in familial PD and describe clinical features of affected patients, genetic findings, and functional consequences. METHODS: Whole exome sequencing was performed in the discovery family proband. Restriction digestion with Bbvl was used to screen SNCA A30G in two validation cohorts. The Greek cohort included 177 familial PD probands, 109 sporadic PD cases, and 377 neurologically healthy controls. The German cohort included 136 familial PD probands, 380 sporadic PD cases, and 116 neurologically healthy controls. We also conducted haplotype analysis using 13 common single nucleotide variants around A30G to determine the possibility of a founder effect for A30G. We then used biophysical methods to characterize A30G αSyn. RESULTS: We identified a novel SNCA A30G (GRCh37, Chr4:90756730, c.89 C>G) mutation that co-segregated with the disease in five affected individuals of three Greek families and was absent from controls. A founder effect was strongly suggested by haplotype analysis. The A30G mutation had a local effect on the intrinsically disordered structure of αSyn, slightly perturbed membrane binding, and promoted fibril formation. CONCLUSION: Based on the identification of A30G co-segregating with the disease in three families, the absence of the mutation in controls and population databases, and the observed functional effects, we propose SNCA A30G as a novel causative mutation for familial PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Circulating Brain-enriched MicroRNAs for detection and discrimination of idiopathic and genetic Parkinson's disease.

BACKGROUND: A minimally invasive test for early detection and monitoring of Parkinson's disease (PD) is a highly unmet need for drug development and planning of patient care. Blood plasma represents an attractive source of biomarkers. MicroRNAs (miRNAs) are conserved noncoding RNA molecules that serve as posttranscriptional regulators of gene expression. As opposed to ubiquitously expressed miRNAs that control house-keeping processes, brain-enriched miRNAs regulate diverse aspects of neuron development and function. These include neuron-subtype specification, axonal growth, dendritic morphogenesis, and spine density. Backed by a large number of studies, we now know that the differential expression of neuron-enriched miRNAs leads to brain dysfunction. OBJECTIVES: The aim was to identify subsets of brain-enriched miRNAs with diagnostic potential for familial and idiopathic PD as well as specify the molecular pathways deregulated in PD. METHODS: Initially, brain-enriched miRNAs were selected based on literature review and validation studies in human tissues. Subsequently, real-time reverse transcription polymerase chain reaction was performed in the plasma of 100 healthy controls and 99 idiopathic and 53 genetic (26 alpha-synucleinA53T and 27 glucocerebrosidase) patients. Statistical and bioinformatics analyses were carried out to pinpoint the diagnostic biomarkers and deregulated pathways, respectively. RESULTS: An explicit molecular fingerprint for each of the 3 PD cohorts was generated. Although the idiopathic PD fingerprint was different from that of genetic PD, the molecular pathways deregulated converged between all PD subtypes. CONCLUSIONS: The study provides a group of brain-enriched miRNAs that may be used for the detection and differentiation of PD subtypes. It has also identified the molecular pathways deregulated in PD. © 2019 International Parkinson and Movement Disorder Society.

Salivary alpha-synuclein as a biomarker for Parkinson's disease: a systematic review.

The search for a reliable, early-disease biomarker for Parkinson's disease (PD) that reflects underlying pathology is a high priority in PD research. Salivary alpha-synuclein (α-Syn) is an easily accessible biomarker for PD with promising results. Our aim was to evaluate the performance of salivary α-Syn as a diagnostic biomarker of PD. We identified 476 studies through a systematic literature review according to PRISMA guidelines. Finally, eight studies reporting data on salivary α-Syn were included in the review (1240 participants). The quality of studies was assessed by Newcastle-Ottawa scale. (1) Three studies showed that the total α-Syn levels were significantly lower in PD patients compared to healthy controls, while in another five there was no significant association. (2) In some studies, total salivary α-Syn was associated with demographic and clinical features; however, no consistent pattern emerged. In one study, total α-Syn levels were associated with poor cognitive performance in PD patients. (3) Four studies showed a higher salivary oligomeric α-Syn and oligomeric α-Syn/total α-Syn ratio in PD compared to healthy controls, while in another four there was no association. (4) One study concluded that genetic polymorphisms may influence total salivary α-Syn in PD patients. Taken together, the potential of salivary total α-Syn as a PD biomarker is still uncertain, whereas salivary oligomeric α-Syn appears quite promising. Pre-analytical and analytical factors of included studies were important limitations to justify the introduction of salivary α-Syn into clinical practice.

123I-FP-CIT SPECT [(123) I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] Imaging in a p.A53T α-synuclein Parkinson's disease cohort versus Parkinson's disease.

BACKGROUND: The p.A53T point mutation in the α-synuclein gene (SNCA) is a rare but highly relevant cause of autosomal dominant Parkinson's disease (PD). OBJECTIVES: The objective of this study was to assess striatal dopaminergic denervation in a cohort of symptomatic carriers of the p.A53T SNCA mutation as compared to PD patients. METHODS: Data from the Parkinson's Progression Markers Initiative database of 11 symptomatic p.A53T SNCA mutation carriers who underwent 123I-FP-CIT SPECT [(123) I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography] imaging at our site were compared with those of 33 age-, sex-, and disease duration-matched PD patients. RESULTS: The p.A53T mutation carriers had significantly lower caudate nucleus binding ratio both contralaterally and ipsilaterally to the most affected side (P = .002 and P = .006) and a decreased contralateral caudate/putamen signal ratio (P = .007) as compared to PD. A similar degree of striatal asymmetry was observed in both subgroups. No correlation between scores in neuropsychological tests and caudate nucleus dopaminergic denervation could be demonstrated. CONCLUSIONS: PD patients harboring the p.A53T SNCA mutation show evidence of a more severe nigrostriatal denervation, especially evident in the caudate nucleus. The lack of significant differences in the putaminal binding ratios may reflect a floor effect or a true preferential targeting of the caudate terminals in p.A53T SNCA-associated PD. © 2018 International Parkinson and Movement Disorder Society.

Motor and Nonmotor Features of Carriers of the p.A53T Alpha-Synuclein Mutation: A Longitudinal Study.

BACKGROUND: G209A SNCA mutation carriers represent an important group of genetic PD. We describe motor and nonmotor features of G209A SNCA mutation carriers. METHODS: Longitudinal clinical assessments over 2 years were collected in 22 symptomatic and 8 asymptomatic G209A SNCA mutation carriers. Motor and nonmotor rating scales were administered. Correlations were performed between clinical variables and disease duration or age. Penetrance was calculated using Kaplan-Meier survival curves. RESULTS: Asymptomatic carriers did not manifest clear premotor symptoms, but symptomatic carriers often reported that olfactory dysfunction and rapid eye movement sleep behavior disorder preceded motor symptoms. Prominent motor decline and deterioration of autonomic and cognitive function occurred at follow-up; such nonmotor features correlated with disease duration, but not age. Disease penetrance was estimated at around 90%. CONCLUSIONS: This study may help to inform clinical trials and provide the basis for studies of disease modifiers in genetic synucleinopathy cohorts. © 2016 International Parkinson and Movement Disorder Society.

Lysosomal alterations in peripheral blood mononuclear cells of Parkinson's disease patients.

BACKGROUND: Reduced expression of lysosomal-associated membrane protein 2a and heatshock-cognate 70 proteins, involved in chaperone-mediated autophagy and of glucocerebrosidase, is reported in PD brains. The aim of this study was to identify systemic alterations in lysosomal-associated membrane protein 2a, heatshock cognate-70, and glucocerebrosidase levels/activity in peripheral blood mononuclear cells from PD patients. METHODS: Protein/mRNA levels were assessed in PD patients from genetically undetermined background, alpha-synuclein (G209A/A53T), or glucocerebrosidase mutation carriers and age-/sex-matched controls. RESULTS: Heatshock cognate 70 protein levels were reduced in all PD groups, whereas its mRNA levels were decreased only in the genetically undetermined group. Glucocerebrosidase protein levels were decreased only in the genetic PD groups, whereas increased mRNA levels and decreased activity were detected only in the glucocerebrosidase mutation group. CONCLUSIONS: Reduced heatshock cognate-70 levels are suggestive of an apparent systemic chaperone-mediated autophagy dysfunction irrespective of genetic background. Glucocerebrosidase activity may serve as a screening tool to identify glucocerebrosidase mutation carriers 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.

Perceptions of Patients, Caregivers, and Healthcare Professionals toward Telemedicine Use for Cognitive and Movement Disorders in the Aegean Islands, Greece: A Pilot Study of the SI4CARE European Project.

BACKGROUND: Patients with neurodegenerative diseases who live in remote areas often have limited access to specialized healthcare, and telemedicine represents a useful solution. The aim of this study was to investigate the perceptions toward the use of a specialized-tertiary telemedicine service of patients with cognitive and movement disorders, caregivers, and local healthcare professionals (HPs) in the Aegean Islands. METHODS: Data were derived from the "Specialized Outpatient Clinic of Memory, Dementia and Parkinson's disease through the National Telemedicine Network", March 2021-March 2023. The survey included 10 questions (5-point Likert scale). RESULTS: We received 64 questionnaires (25 patients, 18 caregivers, 21 HPs). Most participants positively perceived all aspects of telemedicine, including comfort (mean ± standard deviation: patients 4.5 ± 0.9, caregivers: 4.8 ± 0.5, HPs: 4.6 ± 0.7), access to specialized care (4.7 ± 0.6, 4.7 ± 0.5, 4.9 ± 0.4), number of transportations (4.6 ± 0.8, 4.6 ± 0.9, 4.8 ± 0.5), adequacy of follow-up (4.6 ± 0.7, 4.4 ± 0.8, 4.2 ± 0.7), future telemedicine selection (4.8 ± 0.4, 4.8 ± 0.4, 4.6 ± 0.6), perceived reliable medical assessment (4.7 ± 0.5, 4.6 ± 0.6, 4.3 ± 0.6), information delivery (4.7 ± 0.6, 4.6 ± 0.5, 4.4 ± 0.9), health status improvement (4.6 ± 0.7, 4.6 ± 0.6, 4.0 ± 0.7), cost (4.6 ± 1, 4.6 ± 1, 5.0 ± 0.2), and general satisfaction (4.8 ± 0.4, 4.7 ± 0.5, 4.5 ± 0.6). The commonest recommendations were more frequent visits, medical specialties, and dissemination of information. CONCLUSIONS: The positive perception of participants highlights the value of telemedicine for specialized healthcare for neurodegenerative disorders, especially in remote areas.

Application of the AT(N) and Other CSF Classification Systems in Behavioral Variant Frontotemporal Dementia.

BACKGROUND: Patients with a frontotemporal lobar degeneration (FTLD) usually manifest with behavioral variant frontotemporal dementia (bvFTD). Alzheimer's disease (AD) may also manifest with a predominant behavioral-dysexecutive syndrome, similar to bvFTD. Cerebrospinal fluid (CSF) biomarkers, such as total tau (τT), phosphorylated tau (τP-181) and amyloid beta with 42 amino-acids (Aß42), can predict AD pathology in vivo. The aim of this study was to compare the τT/Aß42 and τP-181/Aß42 ratios, the BIOMARKAPD/ABSI criteria and the AT(N) classification system in a cohort of bvFTD patients. METHODS: A total of 105 bvFTD patients (21 possible bvFTD; 20%) with CSF data, examined from 2008 to 2022, were included. Seventy-eight AD patients and 62 control subjects were included. The CSF biomarkers were measured with Innotest (2008-2017 subcohort) and EUROIMMUN (2017-2022 subcohort) ELISAs. RESULTS: Depending on the classification system, 7.6 to 28.6% of bvFTD had an AD biochemical profile. The τT/Aß42 and τP-181/Aß42 ratios classified more patients as AD compared to the BIOMARKAPD/ABSI and AT(N) systems. The patients with possible bvFTD had higher frequencies of AD compared to the probable bvFTD patients. CONCLUSIONS: The four classification criteria of CSF AD biomarkers resulted in differences in AD allocation in this bvFTD cohort. A consensus on the optimal classification criteria of CSF AD biomarkers is pivotal.

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.